Optometry and Vision Sciences - Research Publications

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    Implantation and Recording of Wireless Electroretinogram and Visual Evoked Potential in Conscious Rats
    Charng, J ; He, Z ; Bui, B ; Vingrys, A ; Ivarsson, M ; Fish, R ; Gurrell, R ; Nguyen, C (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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    A Model of Glaucoma Induced by Circumlimbal Suture in Rats and Mice
    He, Z ; Zhao, D ; van Koeverden, AK ; Nguyen, CT ; Lim, JKH ; Wong, VHY ; Vingrys, AJ ; Bui, BV (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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    Tear film inflammatory cytokine upregulation in contact lens discomfort
    Gad, A ; Vingrys, AJ ; Wong, CY ; Jackson, DC ; Downie, LE (ELSEVIER, 2019-01-01)
    PURPOSE: To investigate the ocular inflammatory response, using clinical and immunological techniques, in people experiencing contact lens (CL) discomfort. METHODS: This study involved 38 adults who were full-time, silicone-hydrogel CL wearers. Participants were categorized into groups based upon a validated CL dry-eye questionnaire (CLDEQ-8) (n = 17 'asymptomatic', CLDEQ-8 score <9; n = 21 'symptomatic', CLDEQ-8 score ≥13). Examinations were performed at two visits (one with, and one without, CL wear), separated by one-week. Testing included: tear osmolarity, ocular redness, tear stability, ocular surface staining, meibography, tear production and tear collection. Tear osmolarity was taken from the inferior-lateral and superior-lateral menisci. The 'Inferior-Superior Osmotic Difference', I-SOD, was the absolute osmolarity difference between these menisci. Concentrations of seven cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-gamma, TNF-alpha) were assayed from basal tears using multiplex cytometric bead array. RESULTS: At baseline, there was no significant difference in key clinical signs between asymptomatic and symptomatic CL wearers (p > 0.05). The I-SOD was greater in symptomatic than asymptomatic CL wearers (23.1 ± 2.6 versus 11.3 ± 1.4 mOsmol/L, p = 0.001). People experiencing CL discomfort had higher tear IL-17A (122.6 ± 23.7 versus 44.0 ± 10.0 pg/mL, p = 0.02) and reduced tear stability (6.3 ± 1.1 versus 10.4 ± 1.6 s, p = 0.03) after several hours of CL wear. Tear IL-17A levels correlated with both the I-SOD (r = 0.43, p = 0.01) and CLDEQ-8 score (r = 0.40, p = 0.01). CONCLUSIONS: CL discomfort occurs in individuals having no clinical dry eye signs, and is associated with higher tear levels of the pro-inflammatory cytokine IL-17A. These findings support an association between the discomfort response and low-grade, ocular surface inflammation.
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    Reversal of functional loss in a rat model of chronic intraocular pressure elevation
    Liu, H-H ; He, Z ; Nguyen, CTO ; Vingrys, AJ ; Bui, BV (WILEY, 2017-01-01)
    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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    Comparing self-reported optometric dry eye clinical practices in Australia and the United Kingdom: is there scope for practice improvement?
    Downie, LE ; Rumney, N ; Gad, A ; Keller, PR ; Purslow, C ; Vingrys, AJ (WILEY-BLACKWELL, 2016-03-01)
    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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    Can HMG Co-A reductase inhibitors ("statins") slow the progression of age-related macular degeneration? The Age-Related Maculopathy Statin Study (ARMSS)
    Guymer, RH ; Dimitrov, PN ; Varsamidis, M ; Lim, LL ; Baird, PN ; Vingrys, AJ ; Robman, L (DOVE MEDICAL PRESS LTD, 2008-01-01)
    Age-related macular degeneration (AMD) is responsible for the majority of visual impairment in the Western world. The role of cholesterol-lowering medications, HMG Co-A reductase inhibitors or statins, in reducing the risk of AMD or of delaying its progression has not been fully investigated. A 3-year prospective randomized controlled trial of 40 mg simvastatin per day compared to placebo in subjects at high risk of AMD progression is described. This paper outlines the primary aims of the Age-Related Maculopathy Statin Study (ARMSS), and the methodology involved. Standardized clinical grading of macular photographs and comparison of serial macular digital photographs, using the International grading scheme, form the basis for assessment of primary study outcomes. In addition, macular function is assessed at each visit with detailed psychophysical measurements of rod and cone function. Information collected in this study will assist in the assessment of the potential value of HMG Co-A reductase inhibitors (statins) in reducing the risk of AMD progression.
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    Tablets at the bedside - iPad-based visual field test used in the diagnosis of Intrasellar Haemangiopericytoma: a case report
    Nesaratnam, N ; Thomas, PBM ; Kirollos, R ; Vingrys, AJ ; Kong, GYX ; Martin, KR (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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    Conscious Wireless Electroretinogram and Visual Evoked Potentials in Rats
    Charng, J ; Nguyen, CT ; He, Z ; Dang, TM ; Vingrys, AJ ; Fish, RL ; Gurrell, R ; Brain, P ; Bui, BV ; Frishman, L (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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    Systemic hypertension is not protective against chronic intraocular pressure elevation in a rodent model
    van Koeverden, AK ; He, Z ; Nguyen, CTO ; Vingrys, AJ ; Bui, BV (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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    Oral Omega-3 Supplementation Lowers Intraocular Pressure in Normotensive Adults
    Downie, LE ; Vingrys, AJ (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018-05-01)
    PURPOSE: Elevated intraocular pressure (IOP) is the major modifiable risk factor for the sight-threatening eye disease, glaucoma. We investigated whether oral omega-3 supplements affect IOP in normotensive adults. METHODS: We undertook a pooled analysis of data from two double-masked, placebo-controlled randomized trials (Australian New Zealand Clinical Trials Registry, ACTRN12614001019695, ACTRN12615000173594) that investigated the efficacy and safety of oral omega-3 supplementation for treating ocular surface inflammation. Recruitment involved adults (n = 105) with IOP <21 mm Hg, and without a current or prior glaucoma diagnosis. Participants were randomly allocated to either an oral omega-3 (∼1000 mg/day eicosapentaenoic acid + ∼500 mg/day docosahexaenoic acid ± 900 mg/day α-linolenic acid) or placebo (olive oil, 1500 mg/day) supplement. IOP was quantified at baseline and after 3 months of supplementation (day 90). Change in IOP, relative to baseline, was compared between groups. RESULTS: At baseline, participants were of similar age (omega-3/placebo groups: mean ± SEM, 33.7 ± 1.7, n = 72/35.6 ± 3.0 years, n = 33), sex (65%/79% female), and had similar IOP (14.3 ± 0.3/13.8 ± 0.5 mm Hg). At day 90, IOP was reduced to 13.6 ± 0.3 mm Hg in the omega-3 group; controls had a slight IOP increase to 14.2 ± 0.4 mm Hg (P < 0.05). CONCLUSIONS: Oral omega-3 supplementation for 3 months significantly reduced IOP in normotensive adults. To our knowledge, this is the first study to report that omega-3 fatty acids lower IOP in humans. TRANSLATIONAL RELEVANCE: These findings justify further investigation into the therapeutic potential of omega-3 supplementation for reducing IOP, to prevent and/or treat conditions with IOP elevation, including ocular hypertension and glaucoma.