Optometry and Vision Sciences - Research Publications
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ItemImplantation and Recording of Wireless Electroretinogram and Visual Evoked Potential in Conscious Rats(JOURNAL OF VISUALIZED EXPERIMENTS, 2016-06-01)The full-field electroretinogram (ERG) and visual evoked potential (VEP) are useful tools to assess retinal and visual pathway integrity in both laboratory and clinical settings. Currently, preclinical ERG and VEP measurements are performed with anesthesia to ensure stable electrode placements. However, the very presence of anesthesia has been shown to contaminate normal physiological responses. To overcome these anesthesia confounds, we develop a novel platform to assay ERG and VEP in conscious rats. Electrodes are surgically implanted sub-conjunctivally on the eye to assay the ERG and epidurally over the visual cortex to measure the VEP. A range of amplitude and sensitivity/timing parameters are assayed for both the ERG and VEP at increasing luminous energies. The ERG and VEP signals are shown to be stable and repeatable for at least 4 weeks post surgical implantation. This ability to record ERG and VEP signals without anesthesia confounds in the preclinical setting should provide superior translation to clinical data.
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ItemA Model of Glaucoma Induced by Circumlimbal Suture in Rats and Mice(Journal of Visualized Experiments, 2018)The circumlimbal suture is a technique for inducing experimental glaucoma in rodents by chronically elevating intraocular pressure (IOP), a well-known risk factor for glaucoma. This protocol demonstrates a step-by-step guide on this technique in Long Evans rats and C57BL/6 mice. Under general anesthesia, a "purse-string" suture is applied on the conjunctiva, around the equator and behind the limbus of the eye. The fellow eye serves as an untreated control. Over the duration of our study, which was a period of 8 weeks for rats and 12 weeks for mice, IOP remained elevated, as measured regularly by rebound tonometry in conscious animals without topical anesthesia. In both species, the sutured eyes showed electroretinogram features consistent with preferential inner retinal dysfunction. Optical coherence tomography showed selective thinning of the retinal nerve fiber layer. Histology of the rat retina in cross-section found reduced cell density in the ganglion cell layer, but no change in other cellular layers. Staining of flat-mounted mouse retinae with a ganglion cell specific marker (RBPMS) confirmed ganglion cell loss. The circumlimbal suture is a simple, minimally invasive and cost-effective way to induce ocular hypertension that leads to ganglion cell injury in both rats and mice.
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ItemReversal of functional loss in a rat model of chronic intraocular pressure elevation(WILEY, 2017-01)PURPOSE: This pilot study considered whether intraocular pressure (IOP) lowering could reverse ganglion cell dysfunction in a rat model of chronic ocular hypertension. METHODS: A circumlimbal suture was applied in one eye to induce ocular hypertension (n = 7) in Long-Evans rats. The contralateral eye served as an untreated control. After 8 weeks of IOP elevation the suture was removed to lower IOP for the remaining 7 weeks. Electroretinogram (ERG) and optical coherence tomography (OCT) were measured at baseline, 2, 4, 8, 12 and 15 weeks. Retinae were collected for histology at week 15. RESULTS: In sutured eyes, IOP was elevated by 7-11 mmHg above control eyes (12 ± 0.2 mmHg [standard error of the mean]). Eight weeks of chronic IOP elevation resulted in a reduction of the ganglion cell mediated positive Scotopic Threshold Response (pSTR, -25 ± 7% of baseline), as well as smaller photoreceptor (-7 ± 4%) and bipolar cell mediated responses (-6 ± 5%). After suture removal, IOP recovered to normal. By 15 weeks the a-wave (0 ± 6%), b-wave (-2 ± 6%) and pSTR had recovered back to baseline (from -25 ± 7% to -4 ± 6%). The retinal nerve fiber layer was thinned by -9 ± 3% at week 8 and showed no further decline at week 15 (-10 ± 2%). Cell numbers in the ganglion cell layer were similar between suture removal and control eyes at week 15 (3543 ± 478 vs 4057 ± 476 cells mm-2 ). CONCLUSIONS: The circumlimbal suture model might be a useful platform to study the reversibility of neuronal dysfunction from chronic IOP challenge.
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ItemComparing self-reported optometric dry eye clinical practices in Australia and the United Kingdom: is there scope for practice improvement?(WILEY-BLACKWELL, 2016-03)PURPOSE: The aim of this study was to compare the self-reported clinical practice behaviours of optometrists in Australia and the United Kingdom (UK) with respect to the diagnosis and management of dry eye disease (DED). We also sought to examine whether the reported practices of clinicians in each region were consistent with current evidence-based recommendations for DED. METHODS: An online survey was distributed to optometrists (Australia, n = 654; UK, n = 1006). Respondents provided information about practice modality, years of optometric experience, preferred diagnostic and management strategies (stratified by DED severity) and the information/evidence base used to guide patient care. RESULTS: A total of 317 completed surveys were received (response rates, Australia: 21%, UK: 17%). Optometrists in both regions demonstrated similarly strong knowledge of tear film assessment and adopted both subjective and objective techniques to diagnose DED. Patient symptoms were considered the most important, valuable and commonly performed assessment by both Australian and UK respondents. UK practitioners valued and utilised conjunctival signs and tear meniscus height assessments more than Australian optometrists (p < 0.05), who placed relatively greater emphasis on sodium fluorescein tear break-up time to diagnose DED (p < 0.05). Clinicians in both locations tailored DED therapy to severity. While practitioners in both regions predominantly managed mild DED with eyelid hygiene and tear supplementation, Australian optometrists indicated prescribing topical corticosteroid therapy significantly more often than UK practitioners for moderate (14% vs 6%) and severe (52% vs 8%) disease (p < 0.05). The major source of information used to guide practitioners' dry eye management practices was continuing education conferences. CONCLUSIONS: This study highlights a range of parallels and divergences in dry eye clinical practice between Australian and UK optometrists. Our data identify both areas of strength in the adoption of evidence-based practice, as well as some potential to improve international translation of dry eye research evidence into practice.
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ItemReversibility of Retinal Ganglion Cell Dysfunction From Chronic IOP Elevation(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2019-09)PURPOSE: To test the hypothesis that the capacity for retinal ganglion cells to functionally recover from chronic IOP elevation is dependent on the duration of IOP elevation. METHODS: IOP elevation was induced in one eye in anesthetized (isoflurane) adult C57BL6/J mice using a circumlimbal suture. Sutures were left in place for 8 and 16 weeks (n = 30 and 28). In two other groups the suture was cut after 8 and 12 weeks (n = 30 and 28), and ganglion cell function (electroretinography) and retinal structure (optical coherence tomography) were assessed 4 weeks later. Ganglion cell density was quantified by counting RBPMS (RNA-binding protein with multiple splicing)-stained cells. RESULTS: With IOP elevation (∼10 mm Hg above baseline), ganglion cell function declined to 75% ± 8% at 8 weeks and 59% ± 4% at 16 weeks relative to contralateral control eyes. The retinal nerve fiber layer was thinner at 8 (84% ± 4%) and 16 weeks (83% ± 3%), without a significant difference in total retinal thickness. Ganglion cell function recovered with IOP normalization (suture removal) at week 8 (97% ± 7%), but not at week 12 (73% ± 6%). Ganglion cell loss was found in all groups (-8% to -13%). CONCLUSIONS: In the mouse circumlimbal suture model, 12 weeks of IOP elevation resulted in irreversible ganglion cell dysfunction, whereas retinal dysfunction was fully reversible after 8 weeks of IOP elevation.
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ItemTablets at the bedside - iPad-based visual field test used in the diagnosis of Intrasellar Haemangiopericytoma: a case report(BIOMED CENTRAL LTD, 2017-04-24)BACKGROUND: In the assessment of a pituitary mass, objective visual field testing represents a valuable means of evaluating mass effect, and thus in deciding whether surgical management is warranted. CASE PRESENTATION: In this vignette, we describe a 73 year-old lady who presented with a three-week history of frontal headache, and 'blurriness' in the left side of her vision, due to a WHO grade III anaplastic haemangiopericytoma compressing the optic chiasm. We report how timely investigations, including an iPad-based visual field test (Melbourne Rapid Field, (MRF)) conducted at the bedside aided swift and appropriate management of the patient. CONCLUSIONS: We envisage such a test having a role in assessing bed-bound patients in hospital where access to formal visual field testing is difficult, or indeed in rapid testing of visual fields at the bedside to screen for post-operative complications, such as haematoma.
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ItemConscious Wireless Electroretinogram and Visual Evoked Potentials in Rats(PUBLIC LIBRARY SCIENCE, 2013-09-12)The electroretinogram (ERG, retina) and visual evoked potential (VEP, brain) are widely used in vivo tools assaying the integrity of the visual pathway. Current recordings in preclinical models are conducted under anesthesia, which alters neural physiology and contaminates responses. We describe a conscious wireless ERG and VEP recording platform in rats. Using a novel surgical technique to chronically implant electrodes subconjunctivally on the eye and epidurally over the visual cortex, we are able to record stable and repeatable conscious ERG and VEP signals over at least 1 month. We show that the use of anaesthetics, necessary for conventional ERG and VEP measurements, alters electrophysiology recordings. Conscious visual electrophysiology improves the viability of longitudinal studies by eliminating complications associated with repeated anaesthesia. It will also enable uncontaminated assessment of drug effects, allowing the eye to be used as an effective biomarker of the central nervous system.
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ItemAn Electrophysiological Comparison of Contrast Response Functions in Younger and Older Adults, and Those With Glaucoma(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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ItemDaily vision testing can expose the prodromal phase of migraine(SAGE PUBLICATIONS LTD, 2018-08)Background Several visual tasks have been proposed as indirect assays of the balance between cortical inhibition and excitation in migraine. This study aimed to determine whether daily measurement of performance on such tasks can reveal perceptual changes in the build up to migraine events. Methods Visual performance was measured daily at home in 16 non-headache controls and 18 individuals with migraine using a testing protocol on a portable tablet device. Observers performed two tasks: luminance increment detection in spatial luminance noise and centre surround contrast suppression. Results Luminance thresholds were reduced in migraine compared to control groups ( p < 0.05), but thresholds did not alter across the migraine cycle; while headache-free, centre-surround contrast suppression was stronger for the migraine group relative to controls ( p < 0.05). Surround suppression weakened at around 48 hours prior to a migraine attack and strengthened to approach their headache-free levels by 24 hours post-migraine (main effect of timing, p < 0.05). Conclusions Daily portable testing of vision enabled insight into perceptual performance in the lead up to migraine events, a time point that is typically difficult to capture experimentally. Perceptual surround suppression of contrast fluctuates during the migraine cycle, supporting the utility of this measure as an indirect, non-invasive assay of the balance between cortical inhibition and excitation.
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ItemSystemic hypertension is not protective against chronic intraocular pressure elevation in a rodent model(NATURE PUBLISHING GROUP, 2018-05-08)High intraocular pressure is the most well documented glaucoma risk factor; however many patients develop and/or show progression of glaucoma in its absence. It is now thought that in some instances, ocular perfusion pressure (blood pressure - intraocular pressure) may be as important as intraocular pressure alone. Thus, systemic hypertension would be protective against glaucoma. Epidemiological studies, however, are inconclusive. One theory of why hypertension may not protect against elevated intraocular pressure in spite of increasing ocular perfusion pressure is that with time, morphological changes to the vasculature and autoregulatory failure outweigh the benefits of improved perfusion pressure, ultimately leading to poor retinal and optic nerve head blood supply. In this study we showed the presence of increased wall:lumen ratio and wall area of the ophthalmic artery in rats with chronic hypertension in addition to failure of retinal autoregulation in response to acute modification of ocular perfusion pressure. Subsequently we found that in spite of dramatically increasing ocular perfusion pressure, chronic systemic hypertension failed to protect retinal structure and function from a rodent model of glaucoma.
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