Optometry and Vision Sciences - Research Publications

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    Optimising visual attention in children with autism spectrum disorder: a comparison of fixation distributions viewing singing and speech
    Abel, LA ; Thompson, GA (Association for Research in Vision and Ophthalmology, 2017-06-01)
    Purpose : Many children with autism spectrum disorder (ASD) are at risk of social isolation and limited social development due to difficulties with gaze and visual attention to people. Studies have shown that children with ASD may prefer music to other stimuli. We hypothesised that a short video of a singer would elicit more attention to the performer, particularly to her face, than a video of her reading a story and that the child’s familiarity with the song and story would enhance attention. Methods : 16 children aged 7-10 (14 M, 2 F) with ASD took part. Stimuli were 4 videos 1 minute long. Content was a favourite song or story of the child, along with a song and story which were the same for all children. The performer, her clothing, lighting and sound level were the same across tasks. Props were a pair of drums for the songs and a storybook of similar size for the stories. Eye movements were recorded with an Eyelink 1000; areas of interest (AOIs) were defined for the face, prop and body. 3-way repeated measures ANOVAs were used to examine the proportion of total dwell time, the proportion of total fixations and pupil area for each AOI in each trial. Results : For dwell time proportion, a significant interaction was found for familiarity*AOI (F=7.45, p=.004), with gaze time to the face being increased for familiar trials (Table 1). Similarly, medium*AOI was significant (F=6.01, p=.013), with increased gaze time to the face and body and decreased time to the prop for the songs (Table 2). The same patterns were seen for proportion of fixation counts to the AOIs (familiarity*AOI F=4.97, p =.016; medium*AOI F=10.33, p=.001). For the pupil, only familiarity and AOI were significant; pupils were larger for familiar stimuli (F=16.70, p=.001) and for the face and prop (F=6.8, p=.015), with the body eliciting less dilation. Conclusions : As hypothesised, the videos of singing attracted children's gaze to the performer more than did those of her reading a story. Familiarity with the material being performed also attracted more attention to her face. Familiarity and gaze to the face also increased arousal, as indexed by pupil dilation. Observation by children with ASD of a singer, particularly one performing their favourite songs, may be a useful intervention for improving their social engagement skills.
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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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    AAV-Mediated CRISPR/Cas Gene Editing of Retinal Cells In Vivo
    Hung, SSC ; Chrysostomou, V ; Li, F ; Lim, JKH ; Wang, J-H ; Powell, JE ; Tu, L ; Daniszewski, M ; Lo, C ; Wong, RC ; Crowston, JG ; Pebay, A ; King, AE ; Bui, BV ; Liu, G-S ; Hewitt, AW (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2016-06)
    PURPOSE: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) has recently been adapted to enable efficient editing of the mammalian genome, opening novel avenues for therapeutic intervention of inherited diseases. In seeking to disrupt yellow fluorescent protein (YFP) in a Thy1-YFP transgenic mouse, we assessed the feasibility of utilizing the adeno-associated virus 2 (AAV2) to deliver CRISPR/Cas for gene modification of retinal cells in vivo. METHODS: Single guide RNA (sgRNA) plasmids were designed to target YFP, and after in vitro validation, selected guides were cloned into a dual AAV system. One AAV2 construct was used to deliver Streptococcus pyogenes Cas9 (SpCas9), and the other delivered sgRNA against YFP or LacZ (control) in the presence of mCherry. Five weeks after intravitreal injection, retinal function was determined using electroretinography, and CRISPR/Cas-mediated gene modifications were quantified in retinal flat mounts. RESULTS: Adeno-associated virus 2-mediated in vivo delivery of SpCas9 with sgRNA targeting YFP significantly reduced the number of YFP fluorescent cells of the inner retina of our transgenic mouse model. Overall, we found an 84.0% (95% confidence interval [CI]: 81.8-86.9) reduction of YFP-positive cells in YFP-sgRNA-infected retinal cells compared to eyes treated with LacZ-sgRNA. Electroretinography profiling found no significant alteration in retinal function following AAV2-mediated delivery of CRISPR/Cas components compared to contralateral untreated eyes. CONCLUSIONS: Thy1-YFP transgenic mice were used as a rapid quantifiable means to assess the efficacy of CRISPR/Cas-based retinal gene modification in vivo. We demonstrate that genomic modification of cells in the adult retina can be readily achieved by viral-mediated delivery of CRISPR/Cas.
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    Towards better estimates of uncorrected presbyopia
    Holden, BA ; Tahhan, N ; Jong, M ; Wilson, DA ; Fricke, TR ; Bourne, R ; Resnikoff, S (WORLD HEALTH ORGANIZATION, 2015-10)
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    The effect of blue-light blocking spectacle lenses on visual performance, macular health and the sleep-wake cycle: asystematic review of the literature
    Lawrenson, JG ; Hull, CC ; Downie, LE (WILEY, 2017-11)
    PURPOSE: Blue-blocking (BB) spectacle lenses, which attenuate short-wavelength light, are being marketed to alleviate eyestrain and discomfort when using digital devices, improve sleep quality and potentially confer protection from retinal phototoxicity. The aim of this review was to investigate the relative benefits and potential harms of these lenses. METHODS: We included randomised controlled trials (RCTs), recruiting adults from the general population, which investigated the effect of BB spectacle lenses on visual performance, symptoms of eyestrain or eye fatigue, changes to macular integrity and subjective sleep quality. We searched MEDLINE, EMBASE, the Cochrane Library and clinical trial registers, until 30 April 2017. Risk of bias was assessed using the Cochrane tool. RESULTS: Three studies (with 136 participants) met our inclusion criteria; these had limitations in study design and/or implementation. One study compared the effect of BB lenses with clear lenses on contrast sensitivity (CS) and colour vision (CV) using a pseudo-RCT crossover design; there was no observed difference between lens types (log CS; Mean Difference (MD) = -0.01 [-0.03, 0.01], CV total error score on 100-hue; MD = 1.30 [-7.84, 10.44]). Another study measured critical fusion frequency (CFF), as a proxy for eye fatigue, on wearers of low and high BB lenses, pre- and post- a two-hour computer task. There was no observed difference between low BB and standard lens groups, but there was a less negative change in CFF between the high and low BB groups (MD = 1.81 [0.57, 3.05]). Both studies compared eyestrain symptoms with Likert scales. There was no evidence of inter-group differences for either low BB (MD = 0.00 [-0.22, 0.22]) or high BB lenses (MD = -0.05 [-0.31, 0.21]), nor evidence of a difference in the proportion of participants showing an improvement in symptoms of eyestrain or eye fatigue. One study reported a small improvement in sleep quality in people with self-reported insomnia after wearing high compared to low-BB lenses (MD = 0.80 [0.17, 1.43]) using a 10-point Likert scale. A study involving normal participants found no observed difference in sleep quality. We found no studies investigating effects on macular structure or function. CONCLUSIONS: We find a lack of high quality evidence to support using BB spectacle lenses for the general population to improve visual performance or sleep quality, alleviate eye fatigue or conserve macular health.
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    Optical coherence tomography predicts 4-year incident diabetic neuropathy
    Srinivasan, S ; Dehghani, C ; Pritchard, N ; Edwards, K ; Russell, AW ; Malik, RA ; Efron, N (WILEY, 2017-07)
    PURPOSE: To examine the capability of optical coherence tomography-derived retinal thickness measures in detecting 4-year incident diabetic peripheral neuropathy (DPN). METHODS: 145 eyes of 145 participants with diabetes but no DPN at baseline were examined for incident DPN. HbA1c levels, nephropathy, neuropathy (DPN), cardiovascular measures, and various retinal thickness measures were examined at baseline and after 4 years. Incidence of DPN was defined as newly developed DPN at follow-up. Baseline factors were assessed by univariate and a step-wise multiple logistic regression, and the predictors were examined for diagnostic capabilities. RESULTS: Of the 145 participants without DPN at baseline, 51 had developed DPN when examined after 4 years (35% incidence). Of the ophthalmic variables, the mean (S.D.) of the overall thickness in the parafovea at baseline was 315 (18) μm in the no DPN group and 306 (18) μm in the 'incidence' group, and the differences were significant, p = 0.005. The superior hemisphere parafovea (mean (S.D.): 318 (17) μm vs 310 (20) μm, p = 0.02) and inferior hemisphere parafovea (313 (19) μm vs 302 (18) μm, p = 0.002) were different in the incident DPN group compared with the no DPN group. When adjusted for age, retinal thickness in the parafovea (AUC = 0.65, p = 0.003, 86% sensitivity and 44% specificity at 321 μm criterion), and body mass index or BMI (AUC = 0.65, p = 0.003, 49% sensitivity and 83% specificity at 29.3 kg m-2 criterion) at baseline were significant predictors for 4-year incident DPN. CONCLUSIONS: A lower retinal thickness at the parafovea and a higher BMI can predict 4-year incident neuropathy in patients with diabetes, with acceptable diagnostic accuracies. This OCT-derived measure may serve as a potential ophthalmic marker in the screening of patients at risk of developing DPN.
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    Toxic anterior segment syndrome in a tertiary Australian healthcare institution
    Lim, CHL ; Wong, NJY ; Ng, CH ; Meusemann, RA ; Daniell, MD ; Symons, RCA (WILEY, 2017-09)
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    Use of a novel contact lens to improve fundal optical coherence tomographic images in keratoconus
    Zhu, EY ; Ioannidis, A ; Harrington, P ; Symons, RCA (WILEY, 2017-09)
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    Omega-3 supplementation is neuroprotective to corneal nerves in dry eye disease: a pilot study
    Chinnery, HR ; Golborne, CN ; Downie, LE (WILEY, 2017-07)
    PURPOSE: To investigate whether oral, long-chain omega-3 (ω-3) essential fatty acid (EFA) supplementation, for 3 months, induces changes to the central corneal sub-basal nerve plexus in dry eye disease and whether nerve alterations correlate with clinical findings. METHODS: This prospective, comparative study involved the final 12 participants enrolled in a randomised, double-masked, placebo-controlled clinical trial of 60 participants with moderate dry eye disease. Participants received either placebo (olive oil 1500 mg/day; n = 4) or ω-3 EFA supplements (~1000 mg/day eicosapentaenoic acid + ~500 mg/day docosahexaenoic acid; n = 8) for 90 days. The main outcome measure was the mean change in central corneal sub-basal plexus nerve parameters between days one and 90, quantified using in vivo confocal microscopy. Secondary outcomes included mean change in tear osmolarity, corneal dendritic cell density and basal epithelial cell density. RESULTS: Compared with baseline, the reduction in OSDI score and tear osmolarity at day 90 were greater in the ω-3 EFA group than the placebo group (OSDI: ω-3 EFA, mean ± SEM: -15.6 ± 2.8 vs placebo: -2.8 ± 4.1 units, t5 = 2.6, p = 0.04; tearosmolarity: ω-3 EFA: -22.63 ± 5.7 vs placebo: -8 ± 2.7 mOsmol/L, t9 = 2.3, p = 0.04). At day 90, corneal total nerve branch density (CTBD: 91.1 ± 8.6 vs 45.1 ± 13.4 branches/mm2 , F1,10 = 14, p = 0.004) and corneal nerve branch density on the main fibre (CNBD: 63.4 ± 6.5 vs 27.9 ± 11.5 branches/mm2 , F1,10 = 6, p = 0.03) were higher in the ω-3 EFA group compared with placebo. Relative to day 1, CNBD (branches/mm2 ) increased at day 90 in the ω-3 EFA group (+20.0 ± 9.2, t8 = 3.2 p = 0.01) compared with placebo (-10.8 ± 3.2). Similar changes were evident for corneal nerve fibre length (CNFL, mm/mm2 ), which increased from baseline at day 90 in the omega-3 EFA group (+2.9 ± 1.6, t8 = 3.4 p = 0.01) compared with placebo (-2.7 ± 0.5). There was a negative correlation between CTBD and tear osmolarity (r10 = -0.70, p = 0.01). No significant changes were observed for basal epithelial cell or corneal dendritic cell density. CONCLUSION: These pilot study findings suggest that ω-3 EFA supplementation imparts neuroprotective effects in the corneal sub-basal plexus that correlate with the extent of tear osmolarity normalisation.
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    A comparison of the self-reported dry eye practices of New Zealand optometrists and ophthalmologists
    Xue, AL ; Downie, LE ; Ormonde, SE ; Craig, JP (WILEY, 2017-03)
    PURPOSE: The aim of this cross-sectional survey was to evaluate the self-reported clinical practices of New Zealand optometrists and ophthalmologists with respect to the diagnosis and management of dry eye disease. It also sought to compare these behaviours with the current research evidence base. METHODS: An anonymous survey was distributed electronically to New Zealand eye care clinicians (optometrists n = 614, ophthalmologists n = 113) to determine practitioner interest in dry eye disease, practice experience, practice modality, preferred diagnostic and management strategies, and information used to guide patient care. RESULTS: Respondents from both professions (response rates, optometrists: 26%, ophthalmologists: 26%) demonstrated similarly strong knowledge of tear film assessment. Ninety percent of respondents ranked patient symptoms and meibomian gland evaluation as the most valuable and common diagnostic approaches. Conversely, standardised grading scales and validated dry eye questionnaires were infrequently adopted. Both professions tailored dry eye management according to severity, indicating eyelid hygiene and non-preserved lubricants as mainstay therapies. Ophthalmologists prescribed systemic tetracyclines significantly more often than optometrists for moderate (48% vs 11%) and severe (72% vs 32%) dry eye (p < 0.05). Continuing education conferences were acknowledged as the primary information source used to guide dry eye management practices by both professions. CONCLUSIONS: Consistent with evidence-based guidelines, New Zealand eye care professionals combine subjective and objective techniques to diagnose and stratify dry eye management according to disease severity. There is potential to improve dissemination of research evidence into clinical practice, with continuing education via professional conferences the favoured mode of delivery.