Effect of darkness on inner retinal hypoxia in diabetes.

It has been postulated that diabetic retinopathy might be initiated by hypoxia during the hours of darkness. Oscillatory potentials, which reflect inner retinal function, are reduced in diabetic patients. We tested the effect of oxygen inhalation on the amplitude of these oscillatory potentials after dark adaptation in seven patients with type 2 diabetes and eight controls. We found that the decreased oscillatory potentials induced by dark adaptation in the diabetic patients increased during oxygen inhalation to an amplitude that was not significantly different from that of the controls before oxygen. Oscillatory potentials in the controls were unaffected by oxygen. This finding strengthens support for the suggestion that diabetic patients might benefit from sleeping with night-time illumination.

The influence of plasma glucose upon pulsatile ocular blood flow in subjects with type II diabetes mellitus.

AIMS/HYPOTHESIS: This study investigated the influence of plasma glucose upon pulsatile ocular blood flow in subjects with Type II (non-insulin-dependent) diabetes mellitus. METHODS: A total of 19 subjects with Type II diabetes and 8 normal control subjects undertook a meal tolerance test after an overnight fast. The pulsatile ocular blood flow, using the Ocular Blood Flow Tonometer, and plasma glucose concentrations were taken at times 0 min, 90 min and 240 min. Blood pressure and glycated haemoglobin concentrations, in the subjects with diabetes, were also measured at time 0 min. Pulsatile ocular blood flow and plasma glucose were also measured at times 0 and 90 min in 5 subjects with Type II diabetes mellitus who remained fasting. RESULTS: It was found that the subjects with diabetes who undertook the meal tolerance test showed a significant increase in both plasma glucose concentrations and pulsatile ocular blood flow from time 0-90 min, followed by a decrease from 90 min to the end of the session at 240 min. (p < 0.001 in each case). Regression analysis showed a significant correlation between the change in pulsatile ocular blood flow and the change in plasma glucose concentration (r = 0.671,p = 0.001). Control subjects showed no significant change in either plasma glucose or pulsatile ocular blood flow during the meal tolerance test. Subjects with diabetes mellitus who remained fasting also showed no significant change in pulsatile ocular blood flow or plasma glucose concentrations. No correlation was found between glycated haemoglobin concentrations or blood pressure and pulsatile ocular blood flow. CONCLUSION/INTERPRETATION: Pulsatile ocular blood flow is influenced by changes in plasma glucose concentrations in Type II diabetes mellitus, indicating that uncontrolled hyperglycaemia might result in a higher pulsatile ocular blood flow than might otherwise be expected.

The pattern electroretinogram (PERG) with contralateral corneal reference.

The pattern electroretinogram (PERG) is a sensitive test for investigation of the proximal retina. For monocular recording, the contralateral corneal reference (CCR) electrode position has been suggested as a possible alternative to the conventional ipsilateral temporal reference (ITR). We therefore compared the effect of these electrode positions on 26 subjects (median age 45.5 years, IQR 24.5-61.5). The signals were recorded monocularly with DTL nylon fibre electrodes. The visual stimuli were high contrast 19' black-white checkerboard patterns, reversing 4 times/s. PERG responses obtained from the CCR gave larger amplitudes and the increase in amplitude was statistically significant (P < 0.001). Because the CCR signal is larger, new normative ranges must be established to avoid false negative results.

The effects of astigmatism and working distance on optic nerve head images using a Heidelberg Retina Tomograph scanning laser ophthalmoscope.

PURPOSE: To determine effects of astigmatism and working distance on optic nerve head images in normal patients using the Heidelberg Retina Tomograph. METHODS: The optic disks of 51 normal healthy subjects, aged 19 to 44 years, were imaged through dilated pupils. Subjects with 0.75 DC or less of astigmatism were imaged without correction at a working distance of 15 mm. They were then re-imaged with a cylindrical correction of +3.00 DC at 90 degrees axis (n = 20). Naturally astigmatic subjects with more than 1.00 DC were imaged without correction and then re-imaged once this was neutralized with their appropriate spectacle prescription (n = 15). The effects of working distance were studied using subjects with 0.75 DC or less (n = 16). Two working distances were used, 15 and 25 mm. At each session the means of three topographic images were taken from which standard deviations and parameters were recorded. Parameters analyzed included cup shape measure, rim area, and inferior temporal rim volume. Z-profile full width at half maximum was calculated from one image per subject for each condition. RESULTS: No significant difference was found in the measured parameters of the optic disk for any astigmatic condition or changes in working distance (P >.05), (paired t test). Both the standard deviation of the mean topographic images and the Z-profile half-maximum width of the axial intensity profile were significantly greater with induced astigmatism of +3.00 DC (P values 0.3 and.00, respectively). CONCLUSIONS: Optic disk parameters are not significantly affected by uncorrected astigmatism (up to 2.50 DC) or working distance. The algorithm used by the Heidelberg Retina Tomograph to generate topographic maps is sufficiently robust that astigmatism up to 2.50 DC does not require correction.

The s-cone PHNR and pattern ERG in primary open angle glaucoma.

PURPOSE: To compare the sensitivity of the photopic negative response (PhNR) from the shortwave (S)-sensitive and the long (L)- and medium (M)-wave-sensitive cone electroretinograms (ERGs), with the pattern electroretinogram (PERG) in the early stages of primary open-angle glaucoma (POAG). METHODS: Eighteen patients under treatment for diagnosed POAG and 19 normal control subjects were investigated. S-cone ERGs were elicited using adaptation to 650-nm light to suppress L-cone activity, and substitution between 450 nm and 535 nm to silence M-cone response at luminances higher than rod saturation. PhNRs from the L&M-cone pathways were elicited by a 200-msec pulse of red light (650 nm) on a continuous blue (450 nm) background. PERGs were recorded in accordance with the International Society for Clinical Electrophysiology of Vision (ISCEV) standard. RESULTS: Each method showed a statistically significant difference in the two groups. The S-cone PhNR was the most sensitive test and provided the most statistically significant results, with the largest area enclosed by the receiver operating characteristic (ROC) curve. CONCLUSIONS: The findings indicate that all three types of ERG may be useful in glaucoma investigation. The L- and M-cone PhNRs may have a role in monitoring established glaucoma. The previously reported high sensitivity of the PERG was confirmed. Extensive diffuse damage to S-cone bipolar and bistratified ganglion cells appears to occur at a very early stage in POAG, owing to a pressure-related mechanism, and the S-cone PhNR was the most sensitive test. It may in future have an important role in diagnosis and monitoring of early glaucoma. Further investigation of this possibility is recommended.

Scotopic sensitivity in dyslexia and requirements for DHA supplementation.

Much interest is shown in reduced scotopic sensitivity in dyslexia and the possible role of docosahexaenoic-acid deficiency as a causative factor. However, we found that significant decreases in scotopic sensitivity are not a general characteristic of dyslexia, which may cast doubt on the value of DHA supplementation.

Methods of investigating a visual deficit in dyslexia.

The evidence for a visual deficit in dyslexia is inconclusive. We have developed several tests to investigate the parallel pathways of the visual system which can be applied to dyslexic subjects. Using the techniques of electroretinography, visual evoked potentials, adaptometry and contrast sensitivity, special protocols have been designed to elicit responses from these parallel pathways. These techniques are also applicable in the investigation of many pathological conditions, and of interest for pure research.

Dyslexia: the link with visual deficits.

Some research reports suggest that visual anomalies may have a causative role in dyslexia, and on this basis certain forms of therapy have been proposed. Recently, we have published the initial results of a matched group study which found dyslexia to be associated with binocular instability, reduced amplitude of accommodation, and reduced contrast sensitivity for both low spatial frequencies and uniform field flicker. The binocular instability was best identified by measuring the vergence amplitude: a modified Dunlop test failed to differentiate reliably between the two groups. Here, we report a significant correlation between flicker threshold and binocular instability, thus linking sensory and motor visual correlates of dyslexia. We also present further new analyses on the interaction between optometric variables and the psychometric measurement of coding skills. The results of these analyses disagree with a recent claim that binocular vision anomalies might cause poor performance at coding tasks. Our studies indicate that visual characteristics are not the major aetiological factors in specific reading difficulty.

The magnocellular deficit hypothesis in dyslexia: a review of reported evidence.

Many reports suggest that the majority of dyslexic children have a measurable disorder of the fast processing pathway of the visual system. This pathway is believed to extend from the retina to the occipital and parietal areas of the brain, and is referred to as the magnocellular (M) or transient pathway. Evidence in support of the magnocellular deficit theory comes from several sources, but is not totally consistent. Histological studies have revealed shrinkage and disorganisation of M cells in the lateral geniculate nucleus of dyslexic subjects. Psychophysical investigations of visual persistence, contrast sensitivity to moving sine wave gratings and flicker sensitivity, report atypical results in dyslexic children, reflecting an apparent deficiency in the transient system, although not all psychophysical studies have demonstrated such a deficiency. Visual evoked potential responses to a wide range of stimuli have been reported to be deficient in dyslexic subjects, but again there are dissenting papers. These reports have been subject to critical review and analysis, new techniques specifically to stimulate the magnocellular pathway are described, and the relevance of this research to tinted lens therapies and clinical reading problems is discussed.

Parvocellular neurons limit motion acuity in human peripheral vision.

It is generally believed that the perception of moving targets is mediated by the magnocellular (M) pathway in primate vision, but evidence is emerging that the parvocellular (P) pathway may also play a role in motion perception. Human peripheral vision is susceptible to anomalous motion perception because of spatial aliasing, and in this study we used this fact to determine if the P pathway can mediate information about low- and high-velocity stimuli. Psychometric functions relating visual performance to stimulus spatial frequency were measured for the directional discrimination of drifting sinusoidal gratings presented at 40 degrees eccentricity. Applying the sampling theorem to our results, we estimated that the Nyquist frequency of the limiting sampling array for directional discrimination is 1.7 cycles per degree. This result was compared with the Nyquist limit and spatial filtering properties of M and P ganglion cells in the human peripheral retina, calculated from histological data on their density and dendritic field size. Our results provide evidence to suggest that the reversed motion illusion in human peripheral vision is due to spatial aliasing by the P ganglion cell mosaic. We conclude that the sampling density of P ganglion cells limits veridical motion acuity in human peripheral vision, even for high-velocity targets. This provides further evidence that the P pathway is involved in processing information about motion.

Effect of pattern glare and colored overlays on a stimulated-reading task in dyslexics and normal readers.

Scotopic sensitivity syndrome or the Irlen syndrome describes symptoms of asthenopia anamolous visual performance experienced while reading that are lessened by colored filters. One putative explantation for this condition relates to pattern glare: a hypersensitivity to repetitive patterns, including lines of print on a page. Experiment 1 used a placebo-controlled paradigm to investigate the effect of pattern glare and colored overlays on performance at a simulated reading visual search task. Despite the fact that the subjects were university students, the results showed a tendency, of border-line significance, to support the conclusion that colored filters seem to improve reading through ameliorating pattern glare. In experiment 2 we compared the prevalence of pattern glare in matched groups of dyslexic children and good readers. The dyslexic group reported more pattern glare, but also reported more glare from a control stimulus. Pattern glare in the dyslexic group was directly correlated with flicker sensitivity. The results are related to recent research on visual processing and ocular-motor function in dyslexia.

An investigation of some sensory and refractive visual factors in dyslexia.

The role of visual factors in dyslexia has been a long-standing source of controversy. Recent research has suggested that there may be a deficit of the transient visual subsystem in dyslexia. The evidence for this hypothesis comes principally from investigations of spatial and temporal contrast sensitivity and visual persistence. This evidence is reviewed and it is noted that previous work has never applied two of these purported "tests of transient function" to the same subject group. The hypothesised transient system deficit in dyslexia was investigated in a study comparing 43 control with 39 dyslexic children who were matched for age, sex, and intelligence. Comprehensive psychometric and optometric data were obtained, including visual acuities and refractive errors. The spatial contrast sensitivity function was determined in such a way as to investigate further the findings of Lovegrove, Martin, Bowling, Blackwood, Badcock and Paxton [(1982) Neuropsychology, 20, 309-315] and Martin and Lovegrove [(1984) Neuropsychologia, 22, 73-77]. It might be expected, from the work of Merigan and Maunsell [(1990) Neuroscience, 5, 347-352], that a better test of magno-cellular function would be to investigate the modulation threshold for a virtually uniform field that was flickering sinusoidally at 10 Hz. This temporal contrast sensitivity was studied in a similar way to Brannan and Williams [(1988) Clinical Vision Sciences, 3, 137-142]. A non-verbal simulated reading visual search task was used to investigate the effect of any visual deficits on a test that was, in its low-level visual requirements, similar to reading. The following factors were found to be significantly associated with dyslexia: reduced visual acuity, impaired flicker detection at 10 Hz, reduced low spatial frequency contrast sensitivity, and slightly slower performance at a simulated reading visual search task. The two alleged "tests of transient function" were only weakly correlated with one another (r = 0.183), suggesting that these variables do not measure the same function. Much of the dyslexic group's slightly slower performance at the simulated reading task could be accounted for by the psychometric variable of visual sequential memory. Like reading, the simulated reading task requires the accurate perception of sequential characters. Hence, it seems unlikely that the low-level visual deficits in the dyslexic group were major causes of their poor reading performance. Alternative explanations for the results are discussed.

The origins of luminance and pattern responses of the pattern electroretinogram.

A luminance response is spatially insensitive and dependent upon temporal contrast. The contribution of luminance to the pattern onset electroretinogram (PERG) can be estimated from the temporal contrast of a pattern's illuminance profile on the retina. A profile can be computed for different spatial frequencies by resynthesising the Fourier transform of the pattern after it has been filtered by the eye's MTF. A pure luminance response does not fully account for the amplitude of the PERG. The residual response is called "pattern specific". After the effects of spatial contrast degradation have been corrected for the response is spatially bandpass tuned with a peak that changes with eccentricity. An optimum foveal stimulus is estimated to be 3.5' arc. The pattern specific response component shows a correlation with inner nuclear and ganglion cell volumes. When the relationship of the luminance ERG with temporal contrast was explored empirically it was found to behave in good approximation to the theoretical predictions.

Investigation of accommodative and binocular function in dyslexia.

The visual correlates of dyslexia are the subject of controversy, and much evidence suggests that they may include some aspects of binocular and accommodative function. These factors were investigated in 43 control and 39 dyslexic children, who were matched for age, sex and performance intelligence quotient. The dyslexic group exhibited significantly lower positive and negative vergence reserves, and vergence instability when the eyes were dissociated at near. Their amplitudes of accommodation also were significantly reduced. However, other measures including dissociated and associated heterophoria and accommodative lag and facility were similar in both groups. The stability of motor ocular dominance, as assessed with a modified Dunlop test, was similar in both groups. The results of a simulated reading visual search task suggested that the vergence and accommodative dysfunction were not a major cause of the dyslexia. Further analyses, using reading-age matched groups, suggested that these ocular motor correlates were not attributable to the better reading performance in the control group. The most likely remaining explanation is that they are, in most cases, non-causal correlates of the dyslexia.

Visual evoked potentials to flash and pattern reversal stimulation after administration of systemic or topical scopolamine.

It has previously been shown that 0.6 mg of scopolamine produces a delay in the flash visual evoked potential of young normal volunteers, while the pattern-reversal response does not change in latency. Recent work has shown that this drug differentially affects parvocellular and magnocellular systems. To investigate this effect, two studies were performed. In the first study, 0.4 mg of scopolamine was injected intramuscularly into 11 young, healthy male volunteers who had fasted overnight. The visual evoked potential was recorded to both binocular flash stimulation and monocular pattern-reversal stimulation by means of a checker-board consisting of 56' checks in a 28 degrees field. Responses were recorded before administration of the drug and then 1, 2, 4 and 6 hours after administration. The scopolamine produced a slowing of the flash P2 latency of approximately 6 ms (p < 0.05) two hours after drug administration. There was no effect on the latency of the flash N2 or pattern-reversal N75 or P100. There was an increase in amplitude of the flash N2-P2 component 6 hours after drug administration and an increase in the amplitude of the N75 and P100 2, 4 and 6 hours after the drug. Further subjects were investigated with the use of topical administration of 0.125% scopolamine applied monocularly. In all studies the other eye acted as a control. The subjects were again young healthy volunteers. The visual evoked potential was recorded to both flash and pattern-reversal stimulation with a checkerboard consisting of 60' checks counterphasing at 2 Hz within a 5 degrees field. Results suggest that systemic scopolamine affects the tectal pathway but has no peripheral effect.

Colour, contrast and the visual evoked potential.

Visual evoked potentials exhibit interesting morphological changes when they are elicited by checkerboards of different spatial and chromatic contrast, counterphasing in the foveal and lower macula field. The characteristic, positive wave of the phase-reversal visual evoked potential, for example, is preceded by an increasingly prominent negative peak as luminance contrast progressively increases above 10% and, at isoluminance, the response to red and green checkerboards becomes a predominantly monophasic negative wave. To study the nature of the morphological change we synthesized these waveforms with a computer simulation consisting of Gaussian components. The amplitudes of positive and negative components were altered until the synthesized response was closely similar to the recorded data. These Gaussian components have response characteristics which are identified with those of magnocellular and parvocellular neurones.

Using a binocular field expander on a wide-field search task.

Five patients with constricted visual fields and good central acuity were fitted with an experimental binocular field expander. They undertook a laboratory visual search task in a stationary horizontal 90 degree field with and without the device. Four of five patients adapted relatively quickly to the inherent optical distortions of the field expander. When this binocular aid was worn search efficiency improved significantly with practice; search time was highly correlated (r = -0.92; p less than 0.01) with information channel capacity in the larger visual field.

Patients' responses to retinitis pigmentosa.

Forty-eight patients with retinitis pigmentosa completed at home a questionnaire about everyday tasks, and recorded their distance visual acuities on reduced Snellen charts. Respondents were asked to assess their own abilities for seven tasks involving visual search and mobility on a 1 to 4 scale. This revealed the relative difficulty of each task for the whole group. Other questions were open-ended to allow respondents to express their individual visual problems and experiences. Several problems came to light that were not amenable to treatment with low vision aids, but should be considered as a guide to the clinician in counseling.

An optical stimulator for studying the topography of electrical and magnetic visual evoked responses.

Visual processing areas cover more than 50% of the cortex in primates, but in humans only about half of this area is projected on gyral crests and thus readily accessible to investigation by evoked potential mapping. However, neuromagnetometry does not reflect the activity of these radial dipoles, but instead it strongly represents tangential dipoles, which may arise from activity within the sulci. It follows that the full exploration of the visual areas can only be achieved by combining these complementary techniques. Software-controlled video stimulators are almost universally used for evoked potential recording, but they generate troublesome interference during neural magnetometry. A simple optical stimulator was therefore designed to project a stimulus into magnetically shielded rooms from a remote situation. The system is capable of providing a wide variety of visual stimuli, including pattern reversal, onset, movement and progressive adjustment of chromatic and achromatic contrast. Evoked responses to complex images and isoluminant colored gratings were studied to demonstrate the performance of this type of system.