Optometry and Vision Sciences - Research Publications

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    Normative retrobulbar measurements of the optic nerve using ultra high field magnetic resonance imaging
    Nguyen, BN ; Cleary, JO ; Glarin, R ; Kolbe, SC ; Moffat, BA ; Ordidge, RJ ; Bui, BV ; McKendrick, AM (Association for Research in Vision and Ophthalmology, 2019-07-01)
    Purpose : We exploit the improved spatial resolution and signal-to-noise gain of ultra high field (7T) magnetic resonance imaging (MRI) with a dedicated eye coil for more accurate morphometric measurements of the optic nerve ~2.5mm behind the globe. Methods : Coronal T2-weighted oblique images (TR=2000ms, TE=64ms, FOV=155mm, matrix=384 x 384, slice thickness=0.7mm, scan time=2’34”) through the optic nerve were obtained in 21 healthy adults (20-41 years, 11 emmetropes: +0.75 to -0.50D, 10 myopes: -4.5 to -12D) using a 7T Siemens Magnetom scanner (Erlangen, Germany) and 6-channel eye coil (MRI.TOOLS GmbH, Berlin, Germany). Horizontal and vertical outer diameter of the optic nerve, subarachnoid space (fluid gap) and optic sheath were measured by hand using biomedical imaging software (OsiriX, Pixmeo, Switzerland) (Figure). Significant motion artefacts were avoided with customised fixation and preparation techniques. Results : Horizontal and vertical measurements were similar so were averaged. Right and left eye diameters did not differ and were highly correlated (optic nerve: Pearson r=0.9, p<0.001; fluid gap: r=0.8, p<0.001; optic sheath: r=0.7, p<0.001); hence we report left eye data only. Optic nerve diameter (average of horizontal and vertical diameters) ranged from 2.8-4.1mm in emmetropes and 1.5-4.2mm in myopes and correlated with refractive error (Spearman r=0.46, p=0.04). Similarly, fluid gap diameter (emmetropes: 3.6-5.5mm, myopes: 2.5-5.6mm), but not optic sheath diameter (emmetropes: 4.5-6.8mm, myopes: 4.2-6.8mm), correlated with refractive error (r=0.47, p=0.03). Conclusions : Ultra high field MRI with thinner slices enables more accurate demarcation of the optic nerve, surrounding fluid/subarachnoid space and optic sheath without overlapping of neighbouring anatomy (minimal partial volume artefact). Our 7T MRI-derived normative measurements of optic nerve, fluid gap and sheath diameter are comparable with published reports in healthy observers obtained at conventional MRI magnetic fields (1.5-3T). Our findings suggest a trend for retrobulbar optic nerve and subarachnoid space, but not optic sheath, to be smaller in high myopes.
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    Orientation of the Temporal Nerve Fiber Raphe in Healthy and in Glaucomatous Eyes
    Bedggood, P ; Nguyen, B ; Lakkis, G ; Turpin, A ; McKendrick, AM (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2017-08)
    PURPOSE: To determine the normal variation in orientation of the temporal nerve fiber raphe, and the accuracy with which it may be predicted or approximated in lieu of direct measurement. METHODS: We previously described an algorithm for automatic measurement of raphe orientation from optical coherence tomography, using the intensity of vertically oriented macular cubes. Here this method was applied in 49 healthy participants (age 19-81 years) and 51 participants with primary open angle glaucoma (age 51-80 years). RESULTS: Mean fovea-disc-raphe angle was 173.5° ± 3.2° (range = 166°-182°) and 174.2° ± 3.4° (range = 166°-184°) in healthy and glaucoma patients, respectively. Differences between groups were not significant. Fovea-disc-raphe angle was not correlated with age or axial length (P > 0.4), showed some symmetry between eyes in glaucoma (R2 = 0.31, P < 0.001), and little symmetry in the healthy group (P = 0.06). Fovea-disc angle was correlated with fovea-raphe angle (R2 = 0.27, P = 0.0001), but was not a good predictor for raphe orientation (average error = 6.8°). The horizontal axis was a better predictor (average error = 3.2°; maximum error = 9.6°), but still gave approximately twice the error previously reported for direct measurement from macular cubes. CONCLUSIONS: There is substantial natural variation in temporal nerve fiber raphe orientation, which cannot be predicted from age, axial length, relative geometry of the disc and fovea, or the contralateral eye. For applications to which the orientation of the raphe is considered important, it should be measured directly.
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    An Electrophysiological Comparison of Contrast Response Functions in Younger and Older Adults, and Those With Glaucoma
    Lek, JJ ; Nguyen, BN ; McKendrick, AM ; Vingrys, AJ (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2019-01)
    PURPOSE: Aging and glaucoma both result in contrast processing deficits. However, it is unclear the extent to which these functional deficits arise from retinal or post-retinal neuronal changes. This study aims to disentangle the effects of healthy human aging and glaucoma on retinal and post-retinal contrast processing using visual electrophysiology. METHODS: Steady-state pattern electroretinograms (PERG) and pattern visual evoked potentials (PVEP) were simultaneously recorded across a range of contrasts (0%, 4%, 9%, 18%, 39%, 73%, 97%; 0.8° diameter checks, 31° diameter checkerboard) in 13 glaucoma patients (67 ± 6 years), 15 older (63 ± 8 years) and 14 younger adults (27 ± 3 years). PERG and PVEP contrast response functions were fit with a linear and saturating hyperbolic model, respectively. PERG and PVEP magnitude, timing (phase), and model fit parameters (slope, semi-saturation constant) were compared between groups. RESULTS: PERG responses were reduced and delayed in older adults relative to younger adults, and further reduced and delayed in glaucoma patients across all contrasts. PVEP signals were also reduced and delayed in glaucoma patients, relative to age-similar (older) controls. However, despite having reduced PERG magnitudes, older adults did not demonstrate reduced PVEP magnitudes. CONCLUSIONS: Older adults with healthy vision demonstrate reduced magnitude and delayed timing in the PERG that is not reflected in the PVEP. In contrast, glaucoma produces functional deficits in both PERG and PVEP contrast response functions. Our results suggest that glaucomatous effects on contrast processing are not a simple extension of those that arise as part of the aging process.
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    Occipital GABA levels in older adults and their relationship to visual perceptual suppression
    Pitchaimuthu, K ; Wu, Q-Z ; Carter, O ; Nguyen, BN ; Ahn, S ; Egan, GF ; McKendrick, AM (NATURE PORTFOLIO, 2017-10-27)
    Several studies have attributed certain visual perceptual alterations in older adults to a likely decrease in GABA (Gamma Aminobutyric Acid) concentration in visual cortex, an assumption based on findings in aged non-human primates. However, to our knowledge, there is no direct evidence for an age-related decrease in GABA concentration in human visual cortex. Here, we estimated visual cortical GABA levels and Glx (combined estimate of glutamate and glutamine) levels using magnetic resonance spectroscopy. We also measured performance for two visual tasks that are hypothesised to be mediated, at least in part, by GABAergic inhibition: spatial suppression of motion and binocular rivalry. Our results show increased visual cortical GABA levels, and reduced Glx levels, in older adults. Perceptual performance differed between younger and older groups for both tasks. When subjects of all ages were combined, visual cortical GABA levels but not Glx levels correlated with perceptual performance. No relationship was found between perception and GABA levels in dorsolateral prefrontal cortex. Perceptual measures and GABA were not correlated when either age group was considered separately. Our results challenge current assumptions regarding neurobiological changes that occur within the aging human visual cortex and their association with certain age-related changes in visual perception.
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    Mismatched summation mechanisms in older adults for the perception of small moving stimuli
    McDougall, TJ ; Nguyen, BN ; McKendrick, AM ; Badcock, DR (PERGAMON-ELSEVIER SCIENCE LTD, 2018-01)
    Previous studies have found evidence for reduced cortical inhibition in aging visual cortex. Reduced inhibition could plausibly increase the spatial area of excitation in receptive fields of older observers, as weaker inhibitory processes would allow the excitatory receptive field to dominate and be psychophysically measureable over larger areas. Here, we investigated aging effects on spatial summation of motion direction using the Battenberg summation method, which aims to control the influence of locally generated internal noise changes by holding overall display size constant. This method produces more accurate estimates of summation area than conventional methods that simply increase overall stimulus dimensions. Battenberg stimuli have a checkerboard arrangement, where check size (luminance-modulated drifting gratings alternating with mean luminance areas), but not display size, is varied and compared with performance for a full field stimulus to provide a measure of summation. Motion direction discrimination thresholds, where contrast was the dependent variable, were measured in 14 younger (24-34 years) and 14 older (62-76 years) adults. Older observers were less sensitive for all check sizes, but the relative sensitivity across sizes, also differed between groups. In the older adults, the full field stimulus offered smaller performance improvements compared to that for younger adults, specifically for the small checked Battenberg stimuli. This suggests aging impacts on short-range summation mechanisms, potentially underpinned by larger summation areas for the perception of small moving stimuli.
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    Spatial vision in older adults: perceptual changes and neural bases
    McKendrick, AM ; Chan, YM ; Nguyen, BN (WILEY, 2018-07)
    PURPOSE: The number of older adults is rapidly increasing internationally, leading to a significant increase in research on how healthy ageing impacts vision. Most clinical assessments of spatial vision involve simple detection (letter acuity, grating contrast sensitivity, perimetry). However, most natural visual environments are more spatially complicated, requiring contrast discrimination, and the delineation of object boundaries and contours, which are typically present on non-uniform backgrounds. In this review we discuss recent research that reports on the effects of normal ageing on these more complex visual functions, specifically in the context of recent neurophysiological studies. RECENT FINDINGS: Recent research has concentrated on understanding the effects of healthy ageing on neural responses within the visual pathway in animal models. Such neurophysiological research has led to numerous, subsequently tested, hypotheses regarding the likely impact of healthy human ageing on specific aspects of spatial vision. SUMMARY: Healthy normal ageing impacts significantly on spatial visual information processing from the retina through to visual cortex. Some human data validates that obtained from studies of animal physiology, however some findings indicate that rethinking of presumed neural substrates is required. Notably, not all spatial visual processes are altered by age. Healthy normal ageing impacts significantly on some spatial visual processes (in particular centre-surround tasks), but leaves contrast discrimination, contrast adaptation, and orientation discrimination relatively intact. The study of older adult vision contributes to knowledge of the brain mechanisms altered by the ageing process, can provide practical information regarding visual environments that older adults may find challenging, and may lead to new methods of assessing visual performance in clinical environments.
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    Acute caffeine ingestion affects surround suppression of perceived contrast
    Nguyen, BN ; Hew, S-A ; Ly, J ; Shin, H-Y ; Wong, JC ; Yeung, E ; McKendrick, AM (SAGE PUBLICATIONS LTD, 2018-01)
    Caffeine is a widely used psychostimulant that is associated with increased acetylcholine levels in mammalian brain and acetycholinesterase antagonism. Acetylcholine, a neuromodulator, plays an important role in the processing of visual information. One key example in human vision, thought to at least partly involve cholinergic neuromodulation, is perceptual surround suppression of contrast, whereby the perceived contrast of a pattern is altered by the presence of a neighbouring pattern. Perceptual surround suppression is weaker with pharmacological administration of donepezil (a centrally-acting acetylcholine enzyme inhibitor) in healthy human observers. Here, we test whether temporarily manipulating caffeine levels (from complete washout to a controlled dose of caffeine) has a similar effect on perceptual surround suppression in 21 healthy young adults (aged 20-24 years, 11 females). Neither ingestion of a caffeine pill nor placebo altered contrast judgments when the target pattern was presented on a uniform grey background ( p=0.54). With caffeine ingestion, perceptual surround suppression strength was reduced relative to baseline (prior to pill ingestion, p=0.003) and placebo ( p=0.029), irrespective of whether the surround was oriented parallel or orthogonal to the central target. While daily habitual caffeine consumption of low-to-moderate doses (<400 mg/day, estimated from a written questionnaire) is not predictive of performance, our study indicates that acute consumption of caffeine on the day of testing influences perceptual surround suppression strength. Perceptual surround suppression is predominantly attributed to inhibitory processes involving the major cortical inhibitory neurotransmitter, gamma-aminobutyric acid. Our results point to the involvement of other neuromodulators, possibly cholinergic, in perceptual surround suppression.
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    Aging alters intraocular but not interocular foveal center surround contrast suppression
    Pitchaimuthu, K ; Nguyen, BN ; McKendrick, AM (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2017-01)
    Numerous previous studies have shown that healthy aging results in increased foveal center surround contrast suppression when the center and surround patterns are presented to both eyes. The mechanistic cause of this observation is not well established. Neurophysiological and psychophysical studies have shown that different mechanisms of parafoveal center surround suppression can be tapped by manipulating viewing conditions to present the center and surround to the same eye (intraocular viewing) or to different eyes (interocular viewing), or by manipulating stimulus parameters such as duration. Here, we tested intraocular and interocular foveal center surround contrast suppression for stimuli of 40 ms and 200 ms duration in 18 younger and 18 older adults. For both groups, foveal intraocular center surround contrast suppression decreased with longer stimulus duration whereas interocular surround suppression did not, confirming contributions from separate mechanisms to these forms of suppression. Intraocular center surround contrast suppression was increased in older adults compared to younger adults; however, interocular suppression was similar in both groups. Our results indicate that aging differentially affects distinct forms of suppression arising at various levels of the visual pathway.
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    Visual Contextual Effects of Orientation, Contrast, Flicker, and Luminance: All Are Affected by Normal Aging
    Nguyen, BN ; McKendrick, AM (FRONTIERS MEDIA SA, 2016-04-18)
    The perception of a visual stimulus can be markedly altered by spatial interactions between the stimulus and its surround. For example, a grating stimulus appears lower in contrast when surrounded by a similar pattern of higher contrast: a phenomenon known as surround suppression of perceived contrast. Such center-surround interactions in visual perception are numerous and arise from both cortical and pre-cortical neural circuitry. For example, perceptual surround suppression of luminance and flicker are predominantly mediated pre-cortically, whereas contrast and orientation suppression have strong cortical contributions. Here, we compare the perception of older and younger observers on a battery of tasks designed to assess such visual contextual effects. For all visual dimensions tested (luminance, flicker, contrast, and orientation), on average the older adults showed greater suppression of central targets than the younger adult group. The increase in suppression was consistent in magnitude across all tasks, suggesting that normal aging produces a generalized, non-specific alteration to contextual processing in vision.
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    Foveal and parafoveal contrast suppression are different: Mechanisms revealed by the study of healthy aging
    Nguyen, BN ; McKendrick, AM (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2016-02)
    Visual contextual effects enable inference regarding neural mechanisms of cortical function, principally because of similarities between the stimulus properties influencing human perception and those modifying primate visual cortical neural responses. Most neurophysiology assesses nonfoveal cellular function and circuitry, while most human studies are foveal. Here we use parafoveal stimuli to measure center-surround perception of contrast in older and younger adults. We measure the influence of both near and far surround because neurophysiology demonstrates different circuitry for these areas. Contrast suppression from the near surround was reduced in older observers, while that from the far surround was intact. Our results are consistent with reduced intracortical inhibition with age and normal extrastriate feedback. Interestingly, in the same older observers, foveal surround suppression of contrast was strengthened relative to younger adults, demonstrating a clear distinction between foveal and parafoveal center-surround behavior. We assume that underlying alterations in cortical neurotransmitter levels with age should not differ substantially between the areas of visual cortex representing foveal and near foveal regions. Consequently, our results suggest regional differences in center-surround circuitry. That older adults have varied contextual effects of visual contrast as a function of retinal eccentricity suggests complex effects of aging on scene and object perception.