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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    Optic nerve tissue displacement during mild intraocular pressure elevation: its relationship to central corneal thickness and corneal hysteresis
    Bedggood, P ; Tanabe, F ; McKendrick, AM ; Turpin, A ; Anderson, AJ ; Bui, BV (WILEY, 2018-07)
    PURPOSE: To determine the extent to which (1) optic nerve tissue is displaced following mild acute elevation of intraocular pressure, and (2) clinically accessible measures at the anterior eye can be used as a surrogate for such displacements. METHODS: We imaged the optic disc of 21 healthy subjects before and after intraocular pressure (IOP) elevation of ~10 mmHg delivered by ophthalmodynamometry. Steady-state tissue displacement during IOP elevation was assessed axially from OCT data, and laterally from SLO data. Recovery from IOP elevation was assessed by tracking a single vertical B-scan through the cup centre. Anatomical structures were demarcated by three masked clinicians to determine lateral shifts for temporal cup edge and central disc vessels, and axial shifts of disc surface and anterior lamina cribrosa. Spatial maps of deformation were constructed within the demarcated cup and disc to assess within-tissue displacement. Measured displacements were correlated with corneal hysteresis, corneal thickness, and IOP. RESULTS: The temporal cup edge moved more temporally with higher baseline IOP (R2  = 0.33, p = 0.006) and with lesser elevation of IOP (R2  = 0.43, p = 0.001); it moved more superiorly for thinner corneas (R2  = 0.35, p = 0.007). Thinner corneas also produced less within-cup deformation, relative to that of the disc (R2  = 0.39, p = 0.004). Axial displacement of the lamina and lateral displacement of vessels were often substantial (lamina 20 ± 15 μm, range 1-60 μm; vessels 37 ± 25 μm, range 2-102 μm) but did not correlate with measured parameters. Recovery from IOP elevation did not take more than 300-400 ms in any subject. CONCLUSIONS: Mild acute elevation of IOP produces large and rapidly reversible shifts in optic nerve tissue in young, healthy eyes. The resulting degree, direction and spatial distribution of cup movement are associated with IOP status and corneal thickness, but not corneal hysteresis.
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    The association between retinal vein pulsation pressure and optic disc haemorrhages in glaucoma
    An, D ; House, P ; Barry, C ; Turpin, A ; McKendrick, AM ; Chauhan, BC ; Manners, S ; Graham, SL ; Yu, D-Y ; Morgan, WH ; Bhattacharya, S (PUBLIC LIBRARY SCIENCE, 2017-07-28)
    PURPOSE: To explore the potential relationship between optic disc haemorrhage, venous pulsation pressure (VPP), ocular perfusion pressures and visual field change in glaucomatous and glaucoma suspect eyes. MATERIALS AND METHODS: This prospective observational study examined 155 open angle glaucoma or glaucoma suspect eyes from 78 patients over 5 years. Patients were followed with 3 monthly non-mydriatic disc photographs, 6 monthly standard automated perimetry and annual ophthalmodynamometry. The number of disc haemorrhages in each hemidisc was counted across the study period. Visual field rate of change was calculated using linear regression on the sensitivity of each location over time, then averaged for the matching hemifield. VPP and central retinal artery diastolic pressure (CRADP) were calculated from the measured ophthalmodynanometric forces (ODF). The difference between brachial artery diastolic pressure (DiastBP) and CRADP was calculated as an index of possible flow pathology along the carotid and ophthalmic arteries. RESULTS: Mean age of the cohort was 71.9 ± 7.3 Years. 76 out of 155 eyes (49%) followed for a mean period of 64.2 months had at least 1 disc haemorrhage. 62 (81.6%) of these 76 eyes had recurrent haemorrhages, with a mean of 5.94 recurrences over 64.2 months. Using univariate analysis, rate of visual field change (P<0.0001), VPP (P = 0.0069), alternative ocular perfusion pressure (CRADP-VPP, P = 0.0036), carotid resistance index (DiastBP-CRADP, P = 0.0108) and mean brachial blood pressure (P = 0.0203) were significantly associated with the number of disc haemorrhages. Using multivariate analysis, increased baseline visual field sensitivity (P = 0.0243, coefficient = 0.0275) was significantly associated with disc haemorrhage, in conjunction with higher VPP (P = 0.0029, coefficient = 0.0631), higher mean blood pressure (P = 0.0113, coefficient = 0.0190), higher carotid resistance index (P = 0.0172, coefficient = 0.0566), and rate of visual field loss (P<0.0001, coefficient = -2.0695). CONCLUSIONS: Higher VPP was associated with disc haemorrhage and implicates the involvement of venous pathology, but the effect size is small. Additionally, a greater carotid resistance index suggests that flow pathology in the ophthalmic or carotid arteries may be associated with disc haemorrhage.
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    Improving Spatial Resolution and Test Times of Visual Field Testing Using ARREST
    Turpin, A ; Morgan, WH ; Mckendrick, AM (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018-09)
    PURPOSE: Correctly classifying progression in moderate to advanced glaucoma is difficult. Pointwise visual field test-retest variability is high for sensitivities below approximately 20 dB; hence, reliably detecting progression requires many test repeats. We developed a testing approach that does not attempt to threshold accurately in areas with high variability, but instead expends presentations increasing spatial fidelity. METHODS: Our visual field procedure Australian Reduced Range Extended Spatial Test (ARREST; a variant of the Bayesian procedure Zippy Estimation by Sequential Testing [ZEST]) applies the following approach: once a location has an estimated sensitivity of <17 dB (a "defect"), it is checked that it is not an absolute defect (<0 dB, "blind"). Saved presentations are used to test extra locations that are located near the defect. Visual field deterioration events are either: (1) decreasing in the range of 40 to 17 dB, (2) decreasing from >17 dB to "defect", or (3) "defect" to blind. To test this approach we used an empirical database of progressing moderate-advanced 24-2 visual fields (121 eyes) that we "reverse engineered" to create visual field series that progressed from normal to the end observed field. ARREST and ZEST were run on these fields with test accuracy, presentation time, and ability to detect progression compared. RESULTS: With specificity for detecting progression matched at 95%, ZEST and ARREST showed similar sensitivity for detecting progression. However, ARREST used approximately 25% to 40% fewer test presentations to achieve this result in advanced visual field damage. ARREST spatially defined the visual field deficit with greater precision than ZEST due to the addition of non-24-2 locations. CONCLUSIONS: Spending time trying to accurately measure visual field locations that have high variability is not productive. Our simulations indicate that giving up attempting to quantify size III white-on-white sensitivities below 17 dB and using the presentations saved to test extra locations should better describe progression in moderate-to-advanced glaucoma in shorter time. TRANSLATIONAL RELEVANCE: ARREST is a new visual field test algorithm that provides better spatial definition of visual field defects in faster test time than current procedures. This outcome is achieved by substituting inaccurate quantification of sensitivities <17 dB with new spatial locations.
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    Relating excitatory and inhibitory neurochemicals to visual perception: A magnetic resonance study of occipital cortex between migraine events
    Chan, YM ; Pitchaimuthu, K ; Wu, Q-Z ; Carter, OL ; Egan, GF ; Badcock, DR ; McKendrick, AM ; Solomon, SG (PUBLIC LIBRARY SCIENCE, 2019-07-10)
    Certain perceptual measures have been proposed as indirect assays of brain neurochemical status in people with migraine. One such measure is binocular rivalry, however, previous studies have not measured rivalry characteristics and brain neurochemistry together in people with migraine. This study compared spectroscopy-measured levels of GABA and Glx (glutamine and glutamate complex) in visual cortex between 16 people with migraine and 16 non-headache controls, and assessed whether the concentration of these neurochemicals explains, at least partially, inter-individual variability in binocular rivalry perceptual measures. Mean Glx level was significantly reduced in migraineurs relative to controls, whereas mean occipital GABA levels were similar between groups. Neither GABA levels, nor Glx levels correlated with rivalry percept duration. Our results thus suggest that the previously suggested relationship between rivalry percept duration and GABAergic inhibitory neurotransmitter concentration in visual cortex is not strong enough to enable rivalry percept duration to be reliably assumed to be a surrogate for GABA concentration, at least in the context of healthy individuals and those that experience migraine.
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    Robot Assistants for Perimetry: A Study of Patient Experience and Performance
    McKendrick, AM ; Zeman, A ; Liu, P ; Aktepe, D ; Aden, I ; Bhagat, D ; Do, K ; Nguyen, HD ; Turpin, A (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2019-06)
    PURPOSE: People enjoy supervision during visual field assessment, although resource demands often make this difficult. We evaluated outcomes and subjective experience of methods of receiving feedback during perimetry, with specific goals to compare a humanoid robot to a computerized voice in participants with minimal prior perimetric experience. Human feedback and no feedback also were compared. METHODS: Twenty-two younger (aged 21-31 years) and 18 older (aged 52-76 years) adults participated. Visual field tests were conducted using an Octopus 900, controlled with the Open Perimetry Interface. Participants underwent four tests with the following feedback conditions: (1) human, (2) humanoid robot, (3) computer speaker, and (4) no feedback, in random order. Feedback rules for the speaker and robot were identical, with the difference being a social interaction with the robot before the test. Quantitative perimetric performance compared mean sensitivity (dB), fixation losses, and false-positives. Subjective experience was collected via survey. RESULTS: There was no significant effect of feedback type on the quantitative measures. For younger adults, the human and robot were preferred to the computer speaker (P < 0.01). For older adults, the experience rating was similar for the speaker and robot. No feedback was the least preferred option of 77% younger and 50% older adults. CONCLUSIONS: During perimetry, a social robot was preferred to a computer speaker providing the same feedback, despite the robot not being visible during the test. Making visual field testing more enjoyable for patients and operators may improve compliance and attitude to perimetry, leading to improved clinical outcomes. TRANSLATIONAL RELEVANCE: Our data suggest that humanoid robots can replace some aspects of human interaction during perimetry and are preferable to receiving no human feedback.
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    Home Monitoring of Retinal Sensitivity on a Tablet Device in Intermediate Age-Related Macular Degeneration
    Adams, M ; Ho, CYD ; Baglin, E ; Sharangan, P ; Wu, Z ; Lawson, DJ ; Luu, CD ; Turpin, A ; McKendrick, AM ; Guymer, RH (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018-09)
    PURPOSE: We determine the feasibility of using a home-based tablet device to monitor retinal sensitivity (RS) in intermediate age-related macular degeneration (iAMD), the benefits of weekly reminders, and the comparison with clinic-based results. METHODS: A customized test for tablets was designed to measure RS (within central 2°) in individuals with iAMD at weekly intervals in their home, with remote data collection. Half of the participants were randomized to receive weekly test reminders. Clinic-based microperimetric macular sensitivity results were compared to tablet results. Participation rates were analyzed at 2 months. RESULTS: Of 38 participants (mean age, 70.3 years) with iAMD enrolled in the study, 21 (55%) were using the tablet-based test at 2 months. Common reasons for inactivity were noncompatible devices (41.1%) or other technology access issues (35.3%). Participants with weekly reminders completed tests more regularly (6.6 ± 3.9 vs. 8.7 ± 4.1 days, P = 0.01), but weekly reminders showed no effect on participation rates (P = 0.69). Mean RS from the tablet device (25.03 ± 2.41 dB) was not significantly different from the clinic-based microperimetry performance (25.21 ± 2.20 dB; P = 0.58). CONCLUSIONS: Regular monitoring of retinal function on a tablet device in a home setting in individuals with iAMD is feasible with results comparable to those of clinic-based microperimetry. Weekly reminders resulted in more frequent testing. Seamless ability to access technology will be important for higher participation rates. TRANSLATIONAL RELEVANCE: The use of home-monitoring on a tablet-device is promising, but adequate support for an older cohort to take up technology is required if such a tool is to be useful for long-term home monitoring.
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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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    Visual Snow: Visual Misperception
    White, OB ; Clough, M ; McKendrick, AM ; Fielding, J (LIPPINCOTT WILLIAMS & WILKINS, 2018-12)
    BACKGROUND: Visual snow (VS) is a constant visual disturbance described as flickering dots occupying the entire visual field. Recently, it was characterized as the defining feature of a VS syndrome (VSS), which includes palinopsia, photophobia, photopsias, entoptic phenomena, nyctalopia, and tinnitus. Sixty percent of patients with VSS also experience migraine, with or without aura. This entity often is considered psychogenic in nature, to the detriment of the patient's best interests, but the high frequency of similar visual symptoms argues for an organic deficit. The purpose of this review is to clarify VSS as a true entity and elaborate the nature of individual symptoms and their relationship to each other. EVIDENCE ACQUISITION: The literature was reviewed with specific regard to the clinical presentation and psychophysical, neurophysiological, and functional imaging studies in patients with defined visual disturbances that comprise VSS. RESULTS: Consideration of the individual symptoms suggests that multiple factors are potentially involved in the development of VSS, including subcortical network malfunction and cortical hyperexcitation. Although there is substantial overlap between VSS and migraine syndromes in terms of co-occurring symptoms, both neurophysiological and neuroimaging studies provide substantial evidence of separate abnormalities of processing, supporting these as separate syndromes. CONCLUSIONS: VSS is likely associated with either hyperactive visual cortices or, alternatively, impaired processing of simultaneous afferent information projecting to cortex. VSS likely results from widespread disturbance of sensory processing resulting in sensory misperception. There may be a number of syndromes associated with impaired sensory processing resulting in sensory misperception, including migraine, persistent perceptual postural dizziness, and tinnitus, which overlap with VSS. Elucidation of abnormality in one defined syndrome may provide a path forward for investigating all.