Associations between neonatal nutrition and visual outcomes in 7-year-old children born very preterm.

PURPOSE: There is uncertainty about the effect of increased neonatal protein intake on neurodevelopmental outcomes following preterm birth. The aim of this study was to assess the effect of a change in neonatal nutrition protocol at a major tertiary neonatal intensive care unit intended to increase protein intake on ophthalmic and visual development in school-age children born very preterm. METHODS: The study cohort comprised children (n = 128) with birthweight <1500 g or gestational age < 30 weeks born at Auckland City Hospital before (OldPro group, n = 55) and after (NewPro group, n = 73) a reformulation of parenteral nutrition that resulted in increased total protein intake during the first postnatal week and decreased carbohydrate, total parenteral fluid and sodium intake. Clinical and psychophysical vision assessments were completed at 7 years' corrected age, including visual acuity, global motion perception (a measure of dorsal stream function), stereoacuity, ocular motility and ocular health. Composite measures of favourable overall visual, binocular and functional visual outcomes along with individual vision measures were compared between the groups using logistic and linear regression models. RESULTS: Favourable overall visual outcome did not differ between the two groups. However, global motion perception was better in the NewPro group (p = 0.04), whereas the OldPro group were more likely to have favourable binocular visual outcomes (60% vs. 36%, p = 0.02) and passing stereoacuity (p = 0.02). CONCLUSIONS: These results indicate subtle but complex associations between early neonatal nutrition after very preterm birth and visual development at school age.

Eye care following pre-school vision screening: Data from the Growing Up in New Zealand study.

AIM: This study aimed to determine adherence with follow-up from the New Zealand pre-school vision screening programme. The study also examined associations between pre-school vision screening outcomes and cognitive measures assessed at the 54-month follow-up in the Growing Up in New Zealand study cohort. METHODS: A cross-sectional retrospective record review of pre-school vision screening outcomes and hospital ophthalmology records with linkage to Growing Up in New Zealand cohort study data. RESULTS: Of 176 children referred from vision screening, 21.6% did not attend a referral appointment. Of 138 children who attended a referral appointment, 21.0% did not attend one or more follow-up appointments. Ethnic differences were observed in attendance at referral appointments (attended Maori 13%, Pacific 22.5%, European/Other 64.5%; not attended Maori 26.3%, Pacific 28.9%, European/Other 44.7%; P = 0.04) and follow-up appointments (attended Maori 11.9%, Pacific 15.6%, European/Other 72.5%; not attended Maori 17.2%, Pacific 48.3%, European/Other 34.5%; P = 0.001). Vision screening outcome was significantly associated with letter naming fluency scores (P = 0.01) but not name and numbers scores (P = 0.05). CONCLUSIONS: Non-attendance at referral and follow-up appointments limits the efficacy of vision screening, particularly for children of Maori and Pacific ethnicity. Children referred from vision screening achieve lower scores on letter naming fluency, a key predictor of reading ability in later childhood. Equity-based improvements are required to ensure that all children referred from vision screening receive appropriate follow-up eye care.

Early onset of age-related changes in the retina of cystine/glutamate antiporter knockout mice.

To determine the role of the cystine/glutamate antiporter on retinal structure and function, retinas of C57Bl/6J wild-type and xCT knockout mice, lacking the xCT subunit of the cystine/glutamate antiporter were examined from 6 weeks to 12 months of age. Fundoscopy, optical coherence tomography (OCT), and whole mount retinal autofluorescence imaging were used to visualise age-related retinal spots. Glial fibrillary acidic protein (GFAP) immunolabelling was used to assess retinal stress. Retinal function was evaluated using full-field and focal electroretinograms. Examinations revealed retinal spots in both wild-type and xCT knockout mice with the number of spots greater at 9 months in the knockout compared to wild-type. OCT confirmed these discrete spots were located at the retinal pigment epithelium (RPE)-photoreceptor junction and did not label with drusen markers. Whole mount lambda scans of the 9 month xCT knockout retinas revealed that the photoreceptor autofluorescence matched the spots, suggesting these spots were retinal debris. GFAP labelling was increased in knockout retinas compared to wild-type indicative of retinal stress, and the discrete spots were associated with migration of microglia/macrophages to the RPE-retina intersection. OCT revealed that the superior retina was thinner at 9 months in knockout compared to wild-type mice due to changes to the outer nuclear and photoreceptor layers. While global retinal function was not affected by loss of xCT, focal changes in retinal function were detected in areas where spots were present. Tother these results suggest that the xCT KO mice exhibit features of accelerated ageing and suggests that this mouse model may be useful for studying the underlying cellular pathways in retinal ageing.

Diagnostic accuracy of the Parr vision test, single crowded Lea symbols and Spot vision screener for vision screening of preschool children aged 4-5 years in Aotearoa/New Zealand.

PURPOSE: Preschool children in New Zealand undergo vision screening to detect amblyopia at 4-5 years of age. The current test, the Parr vision test, does not meet international visual acuity chart guidelines and has not been validated against other commonly used paediatric vision tests. New Zealand vision screening protocols are also not targeted for detecting other eye conditions such as uncorrected refractive error, which may affect school performance. We compared the Parr vision test with the single crowded Lea symbols and the Spot vision screener for detecting ocular pathology, refractive error and amblyopic risk factors in preschool children. METHODS: A cross-sectional diagnostic accuracy study recruited children aged 4-5 years via convenience sampling from the University of Auckland Optometry Clinic and through primary schools in Auckland, New Zealand. Participants received vision screening with the three different instruments administered by a lay screener. Comprehensive eye examinations were completed by a paediatric optometrist to determine the presence of vision disorders. RESULTS: Of 197 children who received a comprehensive eye examination, 14 (7.1%) had amblyopic risk factors and 43 (21.8%) had significant refractive error (15.7% with astigmatism, 9.1% with hyperopia). The sensitivity for detecting any ocular condition did not differ significantly between the tests (50.0% for Parr, 43.5% for Lea, 42.5% for Spot). Specificity was significantly lower for the Parr vision test (80.8%) than for the Lea symbols (93.4%) and Spot vision screener (98.0%). Adding the Spot vision screener to measurements of visual acuity significantly improved sensitivity in detecting any ocular condition with the Parr vision test (67.5% for Parr/Spot vs 50% for Parr alone), but not with the Lea symbols (52.5% for Lea/Spot vs 43.5% for Lea alone). CONCLUSION: The sensitivity of the Parr vision test for detecting ocular conditions in preschool children does not vary significantly from that achieved by the Lea symbols or the Spot vision screener. However, current New Zealand vision screening protocols could be improved by expanding the target conditions to include significant refractive error and incorporating the use of the Spot vision screener to increase the accuracy with which children with refractive error are identified. Future research should include longitudinal studies to determine the effect of preschool vision screening on later ocular and academic outcomes.

Vision screening in New Zealand pre-school children: Is it equitable?

AIM: This study aimed to investigate the variability by ethnicity, socio-economic status and location in coverage and testability of the universal B4 School Check vision screening in children aged 4-5 years in New Zealand. METHODS: Aggregated data from 1 July 2011 to 30 June 2015 were sourced from the Statistics New Zealand Integrated Data Infrastructure. Sourced data were attendance at vision screening and record of visual acuity measurement stratified by ethnicity, socio-economic status and region. Children who attended screening were compared with the eligible population (n = 252 279) to calculate coverage. Testability was determined by comparing the children with a recorded visual acuity measurement in each eye with those who attended screening. RESULTS: Overall vision screening coverage was 89.5% and testability was 97.8%. Ethnic differences were evident for coverage (85.7% in Pacific children, 92.5% in European children) and testability (96.4% in Maori children, 98.4% in European children). Socio-economic differences were also observed for coverage (86.4% in most deprived areas, 92.4% in least deprived), testability (most deprived 96.3%, least deprived 98.7%) and by region (coverage range of 80.4-96.4% and testability range of 93.2-99.3%). CONCLUSIONS: Significant disparities exist in vision screening coverage and testability for New Zealand pre-school children. Equity-focused initiatives are required to improve outcomes for children from Maori and Pacific families, and those from households in lower socio-economic areas. Understanding region-specific challenges and successes could support more equitable access to vision screening between regions. Further research is required to determine sources of inequities and to investigate interactions between ethnicity, socio-economic status and location.

Effects of Neonatal Hyperglycemia on Retinopathy of Prematurity and Visual Outcomes at 7 Years of Age: A Matched Cohort Study.

OBJECTIVE: To determine whether neonatal hyperglycemia is associated with retinopathy of prematurity (ROP), visual outcomes, and ocular growth at 7 years of age. STUDY DESIGN: Children born preterm (<30 weeks of gestational age) at a tertiary hospital in Auckland, New Zealand, who developed neonatal hyperglycemia (2 blood glucose concentrations ≥153 mg/dL [8.5 mmol/L] 4 hours apart) were matched with children who were not hyperglycemic (matching criteria: sex, gestational age, birth weight, age, socioeconomic status, and multiple birth) and assessed at 7 years of corrected age. The primary outcome, favorable overall visual outcome (visual acuity ≤0.3 logarithm of the minimum angle of resolution, no strabismus, stereoacuity ≤240 arcsec, not requiring spectacles) was compared between groups using generalized matching criteria-adjusted linear regression models. RESULTS: Assessments were performed on 57 children with neonatal hyperglycemia (hyperglycemia group) and 54 matched children without hyperglycemia (control group). There were no differences in overall favorable visual outcome (OR 0.95, 95% CI 0.42-2.13, P = .90) or severe ROP incidence (OR 2.20, 95% CI 0.63-7.63, P = .21) between groups. Children with hyperglycemia had poorer binocular distance visual acuity (mean difference 0.08, 95% CI 0.03-0.14 logarithm of the minimum angle of resolution, P < .01), more strabismus (OR 6.22, 95% CI 1.31-29.45, P = .02), and thicker crystalline lens (mean difference 0.14, 95% CI 0.04-0.24 mm, P < .01). Maximum blood glucose concentration was greater in the ROP-treated group compared with the ROP-not treated and no ROP groups after adjusting for sex, gestational age, and birth weight z score (P = .02). CONCLUSIONS: Neonatal hyperglycemia was not associated with overall visual outcomes at 7 years of age. However, there were between-group differences for specific outcome measures relating to interocular lens growth and binocular vision. Further follow-up is required to determine implications on long-term visual outcome.

The Effect of Combined Patching and Citalopram on Visual Acuity in Adults with Amblyopia: A Randomized, Crossover, Placebo-Controlled Trial.

Nonhuman animal models have demonstrated that selective serotonin reuptake inhibitors (SSRIs) can enhance plasticity within the mature visual cortex and enable recovery from amblyopia. The aim of this study was to test the hypothesis that the SSRI citalopram combined with part-time patching of the fellow fixing eye would improve amblyopic eye visual acuity in adult humans. Following a crossover, randomized, double-blind, placebo-controlled design, participants completed two 2-week blocks of fellow fixing eye patching. One block combined patching with citalopram (20 mg/day) and the other with a placebo tablet. The blocks were separated by a 2-week washout period. The primary outcome was change in amblyopic eye visual acuity. Secondary outcomes included stereoacuity and electrophysiological measures of retinal and cortical function. Seven participants were randomized, fewer than our prespecified sample size of 20. There were no statistically significant differences in amblyopic eye visual acuity change between the active (mean ± SD change = 0.08 ± 0.16 logMAR) and the placebo (mean change = -0.01 ± 0.03 logMAR) blocks. No treatment effects were observed for any secondary outcomes. However, 3 of 7 participants experienced a 0.1 logMAR or greater improvement in amblyopic eye visual acuity in the active but not the placebo blocks. These results from a small sample suggest that larger-scale trials of SSRI treatment for adult amblyopia may be warranted. Considerations for future trials include drug dose, treatment duration, and recruitment challenges. This study was preregistered as a clinical trial (ACTRN12611000669998).

Recognition acuity in children measured using The Auckland Optotypes.

PURPOSE: Sloan letters displayed by the Electronic Visual Acuity (EVA) system are the gold standard for recognition acuity measurement in research settings. However, letters are not always appropriate for children. The Auckland Optotypes (TAO) are a new, open-access set of 10 pictograms available in regular and vanishing formats. We sought to assess feasibility of using both formats of TAO for measuring visual acuity (VA) in children using a Bayesian adaptive staircase, in a community setting. METHODS: We tested 121 children (5-12 years old) with both formats of TAO, a handheld flipchart vision screener (Parr vision test), as well as the gold standard EVA. We measured feasibility of the three comparison tests in three ways. First, using limits of agreement (LoA) with EVA, second, calculating area under the receiver operating characteristic curve (AUC), and finally, investigating trial-by-trial responses. RESULTS: Agreement between tests was within test-retest reliability of EVA measures (LoATAOregular  = ±0.14, LoATAOvanishing  = ±0.15, LoAParr  = ±0.16 logMAR). TAO tests were highly effective at identifying children with vision impairment (AUCTAOregular  = 0.96, AUCTAOvanishing  = 0.95), whereas Parr was less effective (AUCParr  = 0.82). In 5-6 year old children there was an enhanced advantage of TAO (AUCTAOregular  = 0.97, AUCTAOvanishing  = 0.98) over Parr (AUCParr  = 0.75). Although each child completed 16 trials, approximately 10 trials were sufficient to achieve excellent LoA, and six trials sufficient for accurate screening. CONCLUSION: Threshold VA assessment and vision screening are feasible using both vanishing and regular formats of TAO.

Optical treatment of amblyopia in older children and adults is essential prior to enrolment in a clinical trial.

PURPOSE: Optical treatment alone can improve visual acuity (VA) in children with amblyopia, thus clinical trials investigating additional amblyopia therapies (such as patching or videogames) for children require a preceding optical treatment phase. Emerging therapies for adult patients are entering clinical trials. It is unknown whether optical treatment is effective for adults with amblyopia and whether an optical correction phase is required for trials involving adults. METHODS: We examined participants who underwent optical treatment in the Binocular Treatment for Amblyopia using Videogames (BRAVO) clinical trial (ANZCTR ID: ACTRN12613001004752). Participants were recruited in three age groups (7 to 12, 13 to 17, or ≥18 years), and had unilateral amblyopia due to anisometropia and/or strabismus, with amblyopic eye VA of 0.30-1.00 logMAR (6/12 to 6/60, 20/40 to 20/200). Corrective lenses were prescribed based on cycloplegic refraction to fully correct any anisometropia. VA was assessed using the electronic visual acuity testing algorithm (e-ETDRS) test and near stereoacuity was assessed using the Randot Preschool Test. Participants were assessed every four weeks up to 16 weeks, until either VA was stable or until amblyopic eye VA improved to better than 0.30 logMAR, rendering the participant ineligible for the trial. RESULTS: Eighty participants (mean age 24.6 years, range 7.6-55.5 years) completed four to 16 weeks of optical treatment. A small but statistically significant mean improvement in amblyopic eye VA of 0.05 logMAR was observed (S.D. 0.08 logMAR; paired t-test p < 0.0001). Twenty-five participants (31%) improved by ≥1 logMAR line and of these, seven (9%) improved by ≥2 logMAR lines. Stereoacuity improved in 15 participants (19%). Visual improvements were not associated with age, presence of strabismus, or prior occlusion treatment. Two adult participants withdrew due to intolerance to anisometropic correction. Sixteen out of 80 participants (20%) achieved better than 0.30 logMAR VA in the amblyopic eye after optical treatment. Nine of these participants attended additional follow-up and four (44%) showed further VA improvements. CONCLUSIONS: Improvements from optical treatment resulted in one-fifth of participants becoming ineligible for the main clinical trial. Studies investigating additional amblyopia therapies must include an appropriate optical treatment only phase and/or parallel treatment group regardless of patient age. Optical treatment of amblyopia in adult patients warrants further investigation.

Functional effects of unilateral open-angle glaucoma on the primary and extrastriate visual cortex.

The purpose of this study was to use functional magnetic resonance imaging (fMRI) to investigate the response of the visual cortex to unilateral primary open-angle glaucoma (POAG). Specifically, we assessed whether regions of V1 and V2 with lost input from the glaucomatous eye had a greater response to input from the nonaffected fellow eye. Nine participants with unilateral POAG causing paracentral visual field defects and four controls participated in the study. We found no evidence for an increased response to the fellow eye in glaucoma-affected regions of the visual cortex; however, in agreement with previous studies, there was a pronounced, retinotopically localized reduction of activation in both the primary (V1) and extrastriate visual cortex (V2), when participants viewed through their glaucomatous eye. Our results suggest a remarkable level of stability within the adult primary and extrastriate visual cortex in response to unilateral neurodegeneration of the optic nerve.

Access to eye care among adults from an underserved community in Aotearoa New Zealand.

CLINICAL RELEVANCE: In all countries, there are population groups that are underserved by eye health services. By exploring access to eye care for these communities, optometrists and other eye care providers can promote equitable access to quality eye care, including strengthening patient relationships, and championing inclusive, people-centred services. BACKGROUND: New Zealand has very few policies to enable access to primary eye health services. The aim of this study was to explore the barriers and facilitators to accessing eye health services among adults from an underserved community in Auckland. METHODS: A qualitative study was conducted using in-depth interviews, drawing on the domains of a widely accepted patient-centred framework for health care access. Twenty-five adults with vision impairment were recruited from a community-based eye clinic in a suburb with high area-level deprivation. Interviews were audio-recorded, transcribed verbatim, coded, and analysed using thematic analysis. RESULTS: Twenty-five participants were interviewed, aged between 47 and 71 years, of whom 13 were female. The participants included 13 Pacific people, 6 Maori, 4 New Zealand Europeans and 2 people of other ethnicities. Thematic analysis revealed five themes describing accessing eye care from a community perspective. Two major themes related to barriers were identified, financial barriers and barriers due to location of services and transport. The facilitators of access were, the ability of individuals to identify available eye health services, the provision of appropriate eye health services, and the crucial role played by whanau (family) in supporting participants to seek eye health services. CONCLUSION: Cost is a major barrier to accessing eye health services in New Zealand. The barriers and facilitators expressed by this underserved community can inform efforts to improve eye health access in New Zealand through people-centred service designs.

OKN-Fast: Objective visual acuity threshold measurement using the optokinetic response.

Visual acuity (VA) is the gold-standard measure for the assessment of visual function, but it is challenging to obtain in non-verbal adults and young children. We present OKN-Fast, an objective, automated method for estimation of VA using a reflexive eye movement called optokinetic nystagmus (OKN) that does not require a verbal response from the patient (VA-OKN). We tested the method in a cohort of healthy adults (n=12) with good vision, who were also blurred using a lens. On average OKN-Fast reduced the number of trials needed to determine threshold by half, as compared to a gold standard trial-by-trial assessment. The VAs determined by OKN and ETDRS were similar when blurred (no statistically significant difference). However, a significant bias of logMAR 0.2 was observed for the good vision condition. VA-OKN was highly repeatable with limits of agreement (LOA) similar to those found for ETDRS charts when blurred. However, this VA-OKN was only moderately correlated with VA measured using a ETDRS chart (r2 = 0.55). These results suggest that further optimization is warranted.Clinical Relevance- This work provides an automated approach for the estimation of visual acuity in non-verbal populations such as young children or non-verbal adults.

Primary eye health services for older adults as a component of universal health coverage: a scoping review of evidence from high income countries.

In pursuit of Universal Health Coverage (UHC) for eye health, countries must strengthen services for older adults, who experience the highest prevalence of eye conditions. This scoping review narratively summarised (i) primary eye health services for older adults in eleven high-income countries/territories (from government websites), and (ii) the evidence that eye health services reduced vision impairment and/or provided UHC (access, quality, equity, or financial protection) (from a systematic literature search). We identified 76 services, commonly comprehensive eye examinations ± refractive error correction. Of 102 included publications reporting UHC outcomes, there was no evidence to support vision screening in the absence of follow-up care. Included studies tended to report the UHC dimensions of access (n=70), equity (n=47), and/or quality (n=39), and rarely reported financial protection (n=5). Insufficient access for population subgroups was common; several examples of horizontal and vertical integration of eye health services within the health system were described. Funding: This work was funded by Blind Low Vision New Zealand for Eye Health Aotearoa.

Vision Bus Aotearoa: a platform for strengthening eye health teaching, research and community partnership.

CLINICAL RELEVANCE: Vision Bus Aotearoa is a fully equipped mobile eye health clinic designed to provide a novel platform for undergraduate optometry clinical training, community eye health research and deliver services to underserved communities. BACKGROUND: Aotearoa New Zealand has inequitable access to eye health care. Vision Bus Aotearoa aims to work in partnership with communities to provide comprehensive mobile primary eye health care services while training optometry students, and integrating community eye health research. METHODS: A description is provided of the governance model which has been involved throughout the project. RESULTS: The process of vehicle manufacture, clinical set-up, funding models and service delivery are described. The aims of the project are detailed in terms of optometry teaching, clinical services in partnership with communities, and research integration and implementation. CONCLUSION: Vision Bus Aotearoa represents a valuable opportunity to deliver mobile eye health care to historically underserved communities, enhance undergraduate optometry teaching and to provide a unique platform for community eye health research.

Objective estimation of fusional reserves using infrared eye tracking: the digital fusion-range test.

CLINICAL RELEVANCE: Horizontal fusional reserves are used in the diagnosis and monitoring of common vergence disorders, such as convergence insufficiency, which can cause asthenopia and impact near work. Infrared eyetracking technology shows promise for obtaining automated and objective measurements of fusional reserves, expanding options for screening, clinical testing, and at-home monitoring/vision training. BACKGROUND: Current clinical tests for fusional reserves rely on subjective judgements made by patients (for diplopia) and clinicians (for eye movements). This paper describes an objective and automated "digital fusion-range test" pilot-tested in adults without current eye disease or binocular vision anomalies. This test combines a consumer-grade infrared eyetracker, a dichoptic display, and custom analyses programs to measure convergence and divergence reserves. METHODS: Twenty-nine adult participants completed the study. Horizontal fusional reserves at 55 cm were measured using prism bars and with our computer-based digital fusion-range test. For the digital test, observers viewed dichoptic targets whose binocular disparity modulated over time (at speeds of 0.5, 1.0, or 2.0 Δ/s) while their eye movements were continuously recorded. Subjective reports of break and recovery (by keyboard button press) were compared to objective estimates extracted from eyetracking recordings (via automated analyses). RESULTS: Objective and subjective measures of break and recovery agreed closely. Clinically small (0.3-2Δ) but statistically significant (p < 0.012) differences were found between measurement types for divergence breaks/recoveries and convergence recoveries. No significant differences were found for convergence breaks (p = 0.11). Such differences are consistent with an average 0.91 (SD 1.66) seconds delay between objective break/recovery and subjective responses. The digital test produced comparable results to the standard clinical prism bar method. CONCLUSION: The digital fusion-range test supports an automated, reliable assessment of horizontal fusional reserves, which do not depend on subjective responses. This technology may prove useful in a variety of clinical and community-based settings.

Geographic access to eye health services in Aotearoa New Zealand: which communities are being left behind?

CLINICAL RELEVANCE: Efforts to provide accessible eye care must consider the extent to which travel-distance may be a barrier for some communities. BACKGROUND: This study aimed to determine the distribution of - and geographic access to - eye health services in Aotearoa New Zealand. We further sought to identify communities who might benefit from provision of eye health services that were more geographically accessible. METHODS: We obtained addresses of optometry and ophthalmology clinics from regulatory bodies and augmented this with online searches. Address locators were created using a Land Information dataset and geocoded using ArcGIS 10.6. A national population was derived using Statistics New Zealand's Integrated Data Infrastructure. We generated population-weighted centroids of each of New Zealand's 50,938 meshblocks and calculated the travel distance along the road network between each clinic and population (meshblock centroid). The proportion of the population living >50 km from each clinic type was calculated; as was the median, inter-quartile range and maximum distance across area-level deprivation quintiles in each district. RESULTS: A national population of 4.88 million was identified, as were addresses for 344 optometry, 46 public ophthalmology and 90 private ophthalmology clinics. Nationally and within each district, travel distance to optometry was shorter than to either type of ophthalmology clinic. The region of Northland - with a high proportion of the population Maori and in the highest quintile of area-level deprivation - had the furthest average distance to travel to optometry and public ophthalmology, while the West Coast region on the South Island had the farthest to travel to private ophthalmology. Several communities were identified where longer distances intersected with higher area-level deprivation. CONCLUSION: Most New Zealanders live within 10 km of eye health services. However, to achieve equitable eye health, strategies are required that make affordable eye health services accessible to communities for whom large travel distances intersect with high deprivation.

Developing culturally safe education practices in optometry schools across Australia and Aotearoa New Zealand.

Access to culturally safe health services is a basic human right, however through the lasting effects of colonisation, oppression, and systemic racism, the individual and community health of Indigenous peoples in Australia and Aotearoa New Zealand have been severely impacted. The Aboriginal and Torres Strait Islander Health and Cultural Safety Strategy of the Australian Health Practitioners Regulation Agency, and the Standards of Cultural Competence and Cultural Safety of the Optometrists and Dispensing Opticians Board of New Zealand, recognise the importance of access to safe health care for Aboriginal, Torres Strait Islander and Maori patients, which encompasses both clinical competency and cultural safety. Universities have an ongoing responsibility to ensure their learning and teaching activities result in graduates being able to provide culturally safe practice. This article highlights the emergence of culturally safe practices in the Australian and Aotearoa New Zealand optometry curricula over the last five years incorporating Indigenous ways of knowing, being and doing into the curricula, understanding the local Indigenous histories and contexts, the adoption of online cultural education modules, and clinical placement partnerships with local Indigenous communities. Whilst there is still much work to do to achieve the goal of graduating culturally safe optometrists, this paper focuses on features that enable or impede progress in the development of culturally safe practices within the optometry programmes to improve eye health equity for Indigenous recognise the diversity of Indigenous cultures across Australia and NZ.

Measuring aniseikonia and investigating neuroplasticity and image factors in amblyopia (MAGNIFY): study protocol for a randomised clinical trial.

BACKGROUND: Aniseikonia represents a potential barrier to neuroplasticity which may limit visual outcomes in children with anisometropic amblyopia. Full correction of refractive error is the first step in standard amblyopia treatment, which corrects for image focus but neglects image size differences. METHODS: The MAGNIFY study is a double-masked, randomised clinical trial investigating the effectiveness of aniseikonia correcting lenses in children at first diagnosis of significant anisometropia. We hypothesis that aniseikonia correction lenses will improve image clarity and reduce the retinal size differences producing better visual acuity and stereoacuity improvements after 15 weeks of optical treatment for children with anisometropia. Eligible children will be randomly allocated to the treatment group (aniseikonia-correcting spectacle lenses) or control group (standard spectacle lenses). Visual acuity and binocular functions will be assessed every 5 weeks during the 15-week optical treatment phase according to standard amblyopia treatment protocol. DISCUSSION: It is possible that correcting aniseikonia along with anisometropia at first diagnosis will promote binocularity as well as increase spectacle adherence by reducing visual discomfort, improving optical treatment outcomes. This could then reduce the need for additional amblyopia treatment such as patching or atropine, reducing the burden on hospital eye departments and potentially improving visual outcomes for children with amblyopia. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000061932 . Registered on 24 January 2020. Protocol 15th November 2019, version one.

Transplantation Without Overimmunosuppression (TWO) study protocol: a phase 2b randomised controlled single-centre trial of regulatory T cell therapy to facilitate immunosuppression reduction in living donor kidney transplant recipients.

INTRODUCTION: Regulatory T cell (Treg) therapy has been demonstrated to facilitate long-term allograft survival in preclinical models of transplantation and may permit reduction of immunosuppression and its associated complications in the clinical setting. Phase 1 clinical trials have shown Treg therapy to be safe and feasible in clinical practice. Here we describe a protocol for the TWO study, a phase 2b randomised control trial of Treg therapy in living donor kidney transplant recipients that will confirm safety and explore efficacy of this novel treatment strategy. METHODS AND ANALYSIS: 60 patients will be randomised on a 1:1 basis to Treg therapy (TR001) or standard clinical care (control). Patients in the TR001 arm will receive an infusion of autologous polyclonal ex vivo expanded Tregs 5 days after transplantation instead of standard monoclonal antibody induction. Maintenance immunosuppression will be reduced over the course of the post-transplant period to low-dose tacrolimus monotherapy. Control participants will receive a standard basiliximab-based immunosuppression regimen with long-term tacrolimus and mycophenolate mofetil immunosuppression. The primary endpoint is biopsy proven acute rejection over 18 months; secondary endpoints include immunosuppression burden, chronic graft dysfunction and drug-related complications. ETHICS AND DISSEMINATION: Ethical approval has been provided by the National Health Service Health Research Authority South Central-Oxford A Research Ethics Committee (reference 18/SC/0054). The study also received authorisation from the UK Medicines and Healthcare products Regulatory Agency and is being run in accordance with the principles of Good Clinical Practice, in collaboration with the registered trials unit Oxford Clinical Trials Research Unit. Results from the TWO study will be published in peer-reviewed scientific/medical journals and presented at scientific/clinical symposia and congresses. TRIAL REGISTRATION NUMBER: ISRCTN: 11038572; Pre-results.

Hormone replacement therapy (conjugated oestrogens plus bazedoxifene) for post-menopausal women with symptomatic hand osteoarthritis: primary report from the HOPE-e randomised, placebo-controlled, feasibility study.

Background: Symptomatic hand osteoarthritis is more common in women than in men, and its incidence increases around the age of menopause, implicating oestrogen deficiency. No randomised controlled trials of hormone replacement therapy (HRT) have been done in people with hand osteoarthritis. We aimed to determine the feasibility and acceptability of a form of HRT (conjugated oestrogens plus bazedoxifene) in post-menopausal women with painful hand osteoarthritis. Methods: The HOPE-e feasibility study was a randomised, double-blind, placebo-controlled trial, for which we recruited women aged 40-65 years, for whom 1-10 years had passed after their final menstrual period, with definite hand osteoarthritis and at least two painful hand joints. Participants were recruited across three primary or secondary care sites and from the community and were randomly assigned (1:1) to receive conjugated oestrogens plus bazedoxifene or placebo, orally once every day for 24 weeks, before weaning for 4 weeks until the end of the study. The primary feasibility outcomes were rates of identification, recruitment, randomisation, retention, and compliance of eligible participants, and the likelihood of unmasking. The secondary objective was to generate proof-of-concept quantitative and qualitative data on the acceptability of proposed clinical outcomes for a full trial and adverse events. We used an intention-to-treat analysis, and criteria for progression to a full trial were pre-defined as recruitment of at least 30 participants across all sites in 18 months; a dropout rate of less than or equal to 30% of randomised individuals; and acceptability to the majority of participants, including acceptable rates of adverse events. Due to the COVID-19 pandemic, the recruitment window was reduced to 12-15 months. A proportionately reduced minimum sample size of 22 was judged to be sufficient to test feasibility. This trial was registered at ISRCTN, ISRCTN12196200. Findings: From May 9, 2019 to Dec 31, 2020, 434 enquiries or referrals were received. We did 96 telephone pre-screens; of the 35 eligible participants, seven were excluded as ineligible at the telephone or face-to-face screening and 28 (80% [95% CI 63-92]) were randomly assigned. Of the 406 who were not randomly assigned, 250 (62%) were ineligible (with contraindicated medications accounting for 50 [20%] of these), 101 (25%) did not respond to further enquiries, and 55 (14%) chose not to proceed (with the most common reason being not wanting to take a hormone-based drug). All 28 randomised participants completed all follow-up assessments with high compliance and outcome measure completeness. All three adverse event-related treatment withdrawals were in the placebo group. No serious adverse events were reported. Participants and investigators were successfully masked (participant Bang's blinding index placebo group 0·50 [95% CI 0·25-0·75]). The trial met the prespecified criteria for progression to a full trial. Interpretation: This first-ever feasibility study of a randomised controlled trial of HRT for post-menopausal women with painful hand osteoarthritis met its progression criteria, although it was not powered to detect a clinical effect. This outcome indicates that a full trial of an HRT in this population is feasible and acceptable and identifies potential refinements with regard to the design of such a trial. Funding: Research for Patient Benefit programme, National Institute for Health Research.