Optometry and Vision Sciences - Research Publications

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    Stem cell therapies for eye conditions: A survey of Australian ophthalmologists
    Cabrera-Aguas, M ; Downie, L ; Munsie, MM ; Watson, SL (WILEY, 2022-02-01)
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    Evaluating the clinical translational relevance of animal models for limbal stem cell deficiency: A systematic review
    Delic, NC ; Cai, JR ; Watson, SL ; Downie, LE ; Di Girolamo, N (ELSEVIER, 2022-01-01)
    PURPOSE: Animal models are pivotal for elucidating pathophysiological mechanisms and evaluating novel therapies. This systematic review identified studies that developed or adapted animal models of limbal stem cell deficiency (LSCD), assessed their reporting quality, summarized their key characteristics, and established their clinical translational relevance to human disease. METHODS: The protocol was prospectively registered (PROSPERO CRD42020203937). Searches were conducted in PubMed, Ovid EMBASE and Web of Science in August 2020. Two authors screened citations, extracted data, assessed the reporting quality of eligible studies using the ARRIVE guidelines, and judged the clinical translational relevance of each model using a custom matrix. RESULTS: 105 studies were included. Rabbits were the most common animal species. Overall, 97% of studies recapitulated LSCD to a clinical etiology, however 62% did not provide sufficient methodological detail to enable independent reproduction of the model. Adverse events and/or exclusion of animals were infrequently (20%) reported. Approximately one-quarter of studies did not produce the intended severity of LSCD; 34% provided insufficient information to assess the fidelity of disease induction. Adjunctive diagnostic confirmation of LSCD induction was performed in 13% of studies. CONCLUSIONS: This is the first systematic review to assess the reporting quality and clinical translational relevance of animal models of LSCD. Models of LSCD have evolved over time, resulting in variable reporting of the characteristics of animals, experimental procedures and adverse events. In most studies, validation of LSCD was made using clinical tests; newer adjunctive techniques would enhance diagnostic validation. As most studies sought to evaluate novel therapies for LSCD, animal models should ideally recapitulate all features of the condition that develop in patients.
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    Interventions for the Management of Computer Vision Syndrome: A Systematic Review and Meta-analysis.
    Singh, S ; McGuinness, MB ; Anderson, AJ ; Downie, LE (Elsevier BV, 2022-05-18)
    TOPIC: To evaluate the efficacy and safety of interventions for treating eye strain related to computer use relative to placebo or no treatment. CLINICAL RELEVANCE: Computer use is pervasive and often associated with eye strain, referred to as computer vision syndrome (CVS). Currently, no clinical guidelines exist to help practitioners provide evidence-based advice about CVS treatments, many of which are marketed directly to patients. This systematic review and meta-analysis was designed to help inform best practice for eye care providers. METHODS: Eligible randomized controlled trials (RCTs) were identified in Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and trial registries, searched from inception through November 23, 2021. Eligible studies were appraised for risk of bias and were synthesized. The certainty of the body of evidence was judged using the Grading of Recommendations, Assessment, Development, and Evaluation system. Standardized mean differences (SMDs) were used when differently scaled measures were combined. RESULTS: Forty-five RCTs, involving 4497 participants, were included. Multifocal lenses did not improve visual fatigue scores compared with single-vision lenses (3 RCTs; SMD, 0.11; 95% confidence interval [CI], -0.14 to 0.37; P = 0.38). Visual fatigue symptoms were not reduced by blue-blocking spectacles (3 RCTs), with evidence judged of low certainty. Relative to placebo, oral berry extract supplementation did not improve visual fatigue (7 RCTs; SMD, -0.27; 95% CI, -0.70 to 0.16; P = 0.22) or dry eye symptoms (4 RCTs; SMD, -0.10; 95% CI, -0.54 to 0.33; P = 0.65). Likewise, berry extract supplementation had no significant effects on critical flicker-fusion frequency (CFF) or accommodative amplitude. Oral omega-3 supplementation for 45 days to 3 months improved dry eye symptoms (2 RCTs; mean difference [MD], -3.36; 95% CI, -3.63 to -3.10 on an 18 unit scale; P < 0.00001) relative to placebo. Oral carotenoid supplementation improved CFF (2 RCTs; MD, 1.55 Hz; 95% CI, 0.42 to 2.67 Hz; P = 0.007) relative to placebo, although the clinical significance of this finding is unclear. DISCUSSION: We did not identify high-certainty evidence supporting the use of any of the therapies analyzed. Low-certainty evidence suggested that oral omega-3 supplementation reduces dry eye symptoms in symptomatic computer users.
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    The effect of topical decorin on temporal changes to corneal immune cells after epithelial abrasion
    Wu, M ; Downie, LE ; Hill, LJ ; Chinnery, HR (BMC, 2022-04-12)
    BACKGROUND: Corneal immune cells interact with corneal sensory nerves during both homeostasis and inflammation. This study sought to evaluate temporal changes to corneal immune cell density in a mouse model of epithelial abrasion and nerve injury, and to investigate the immunomodulatory effects of topical decorin, which we have shown previously to promote corneal nerve regeneration. METHODS: Bilateral corneal epithelial abrasions (2 mm) were performed on C57BL/6J mice. Topical decorin or saline eye drops were applied three times daily for 12 h, 24 h, 3 days or 5 days. Optical coherence tomography imaging was performed to measure the abrasion area. The densities of corneal sensory nerves (β-tubulin III) and immune cells, including dendritic cells (DCs; CD11c+), macrophages (Iba-1+) and neutrophils (NIMP-R14+) were measured. Cx3cr1gfp/gfp mice that spontaneously lack resident corneal intraepithelial DCs were used to investigate the specific contribution of epithelial DCs. Neuropeptide and cytokine gene expression was evaluated using qRT-PCR at 12 h post-injury. RESULTS: In decorin-treated corneas, higher intraepithelial DC densities and lower neutrophil densities were observed at 24 h after injury, compared to saline controls. At 12 h post-injury, topical decorin application was associated with greater re-epithelialisation. At 5 days post-injury, corneal stromal macrophage density in the decorin-treated and contralateral eyes was lower, and nerve density was higher, compared to eyes treated with saline only. Lower expression of transforming growth factor beta (TGF-β) and higher expression of CSPG4 mRNA was detected in corneas treated with topical decorin. There was no difference in corneal neutrophil density in Cx3cr1gfp/gfp mice treated with or without decorin at 12 h. CONCLUSIONS: Topical decorin regulates immune cell dynamics after corneal injury, by inhibiting neutrophils and recruiting intraepithelial DCs during the acute phase (< 24 h), and inhibiting macrophage density at the study endpoint (5 days). These immunomodulatory effects were associated with faster re-epithelialisation and likely contribute to promoting sensory nerve regeneration. The findings suggest a potential interaction between DCs and neutrophils with topical decorin treatment, as the decorin-induced neutrophil inhibition was absent in Cx3cr1gfp/gfp mice that lack corneal epithelial DCs. TGF-β and CSPG4 proteoglycan likely regulate decorin-mediated innate immune cell responses and nerve regeneration after injury.
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    Optical coherence tomography: seeing the unseen
    Bui, B ; Downie, LE ; Lindsay, RG (TAYLOR & FRANCIS LTD, 2019-05-01)
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    Citizen Science Models in Health Research: an Australian Commentary.
    Borda, A ; Gray, K ; Downie, L (University of Illinois Libraries, 2019)
    This qualitative review explores how established citizen science models can inform and support meaningful engagement of public in health research in Australia. In particular, with the growth in participatory health research approaches and increasing consumer participation in contributing to this research through digital technologies, there are gaps in our understanding of best practice in health and biomedical citizen science research to address these paradigm shifts. Notable gaps are how we might more clearly define the parameters of such research and which citizen science models might best support digitally-enabled participation falling within these. Further work in this area is expected to lead to how established citizen science methods may help improve the quality of and the translation of public engagement in health research.
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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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    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, 2017-11-01)
    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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    Omega-3 supplementation is neuroprotective to corneal nerves in dry eye disease: a pilot study
    Chinnery, HR ; Golborne, CN ; Downie, LE (WILEY, 2017-07-01)
    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, 2017-03-01)
    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.