Ophthalmology (Eye & Ear Hospital) - Research Publications
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ItemLow-concentration atropine eyedrops for myopia control in a multi-racial cohort of Australian children: A randomised clinical trial(WILEY, 2022-12)BACKGROUND: To test the hypothesis that 0.01% atropine eyedrops are a safe and effective myopia-control approach in Australian children. METHODS: Children (6-16 years; 49% Europeans, 18% East Asian, 22% South Asian, and 12% other/mixed ancestry) with documented myopia progression were enrolled into this single-centre randomised, parallel, double-masked, placebo-controlled trial and randomised to receive 0.01% atropine (n = 104) or placebo (n = 49) eyedrops (2:1 ratio) instilled nightly over 24 months (mean index age = 12.2 ± 2.5 and 11.2 ± 2.8 years, respectively). Outcome measures were the changes in spherical equivalent (SE) and axial length (AL) from baseline. RESULTS: At 12 months, the mean SE and AL change from baseline were -0.31D (95% confidence interval [CI] = -0.39 to -0.22) and 0.16 mm (95%CI = 0.13-0.20) in the atropine group and -0.53D (95%CI = -0.66 to -0.40) and 0.25 mm (95%CI = 0.20-0.30) in the placebo group (group difference p ≤ 0.01). At 24 months, the mean SE and AL change from baseline was -0.64D (95%CI = -0.73 to -0.56) and 0.34 mm (95%CI = 0.30-0.37) in the atropine group, and -0.78D (95%CI = -0.91 to -0.65) and 0.38 mm (95%CI = 0.33-0.43) in the placebo group. Group difference at 24 months was not statistically significant (p = 0.10). At 24 months, the atropine group had reduced accommodative amplitude and pupillary light response compared to the placebo group. CONCLUSIONS: In Australian children, 0.01% atropine eyedrops were safe, well-tolerated, and had a modest myopia-control effect, although there was an apparent decrease in efficacy between 18 and 24 months, which is likely driven by a higher dropout rate in the placebo group.
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ItemThe Relationship Between Fetal Growth and Retinal Nerve Fiber Layer Thickness in a Cohort of Young Adults(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2022-07)PURPOSE: To explore relationships between patterns of fetal anthropometric growth, as reflective of fetal wellbeing, and global retinal nerve fiber layer (RNFL) thickness measured in young adulthood. METHODS: Participants (n = 481) from within a Western Australian pregnancy cohort study underwent five serial ultrasound scans during gestation, with fetal biometry measured at each scan. Optic disc parameters were measured via spectral-domain optical coherence tomography imaging at a 20-year follow-up eye examination. Generalized estimating equations were used to evaluate differences in global RNFL thickness between groups of participants who had undergone similar growth trajectories based on fetal head circumference (FHC), abdominal circumference (FAC), femur length (FFL), and estimated fetal weight (EFW). RESULTS: Participants with consistently large FHCs throughout gestation had significantly thicker global RNFLs than those with any other pattern of FHC growth (P = 0.023), even after adjustment for potential confounders (P = 0.037). Based on model fit statistics, FHC growth trajectory was a better predictor of global RNFL thickness than birth weight or head circumference at birth. RNFL thickness did not vary significantly between groups of participants with different growth trajectories based on FAC, FFL, or EFW. CONCLUSIONS: FHC growth is associated with RNFL thickness in young adulthood and, moreover, is a better predictor than either birth weight or head circumference at birth. TRANSLATIONAL RELEVANCE: This research demonstrates an association between intrauterine growth and long-term optic nerve health, providing a basis for further exploring the extent of the influence of fetal wellbeing on clinical conditions linked to RNFL thinning.
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ItemChoroidal Thickening During Young Adulthood and Baseline Choroidal Thickness Predicts Refractive Error Change.(Association for Research in Vision and Ophthalmology (ARVO), 2022-05-02)PURPOSE: The purpose of this study was to explore the age-related change in choroidal thickness (ChT) and test the hypothesis that baseline ChT is predictive of refractive error change in healthy young adults. METHODS: Participants underwent spectral-domain optical coherence tomography (SD-OCT) imaging and autorefraction at 20 (baseline) and 28 years old. The enhanced depth imaging mode on the SD-OCT was used to obtain images of the choroid. Scans were exported from the SD-OCT and analyzed with a custom software that automatically measures the central ChT. The longitudinal change in subfoveal ChT and association between baseline subfoveal ChT and 8-year change in refractive error (spherical equivalent) were determined using linear mixed models. RESULTS: In total, 395 eyes of 198 participants (44% men; 18-22 years at baseline) were included. Over 8 years, mean spherical equivalent decreased by 0.25 diopters (D) and axial length increased by 0.09 mm. Subfoveal choroid thickened by 1.3 µm/year (95% confidence interval [CI] = 0.6-2.0), but this was reduced by 0.9 µm/year (95% CI = 1.6-0.2) for every 1 mm increase in axial length. For every 10 µm increase in baseline ChT, average annual change in spherical equivalent and axial length reduced by 0.006 D/year and 0.003 mm/year, respectively. CONCLUSIONS: In a community-based cohort of young adults, the choroid continued to change during early adulthood. Choroidal thickening was less in eyes that were longer at baseline, and the choroid thinned in eyes that showed myopia progression. The association between baseline ChT and longitudinal changes in spherical equivalent and axial length supports the hypothesis that ChT may be predictive of refractive error development and/or myopia progression.
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ItemThe effect of transverse ocular magnification adjustment on macular thickness profile in different refractive errors in community-based adults(PUBLIC LIBRARY SCIENCE, 2022)PURPOSE: Changes in retinal thickness are common in various ocular diseases. Transverse magnification due to differing ocular biometrics, in particular axial length, affects measurement of retinal thickness in different regions. This study evaluated the effect of axial length and refractive error on measured macular thickness in two community-based cohorts of healthy young adults. METHODS: A total of 2160 eyes of 1247 community-based participants (18-30 years; 23.4% myopes, mean axial length = 23.6mm) were included in this analysis. Macular thickness measurements were obtained using a spectral-domain optical coherence tomography (which assumes an axial length of 24.385mm). Using a custom program, retinal thickness data were extracted at the 9 Early Treatment of Diabetic Retinopathy Study (ETDRS) regions with and without correction for transverse magnificent effects, with the corrected measurements adjusting according to the participant's axial length. Linear mixed models were used to analyse the effect of correction and its interaction with axial length or refractive group on retinal thickness. RESULTS: The raw measures (uncorrected for axial length) underestimated the true retinal thickness at the central macula, while overestimating at most non-central macular regions. There was an axial length by correction interaction effect in all but the nasal regions (all p<0.05). For each 1mm increase in axial length, the central macular thickness is overestimated by 2.7-2.9μm while thicknesses at other regions were underestimated by 0.2-4.1μm. Based on the raw thickness measurements, myopes have thinner retinas than non-myopes at most non-central macular. However, this difference was no longer significant when the corrected data was used. CONCLUSION: In a community-based sample, the raw measurements underestimate the retinal thickness at the central macula and overestimate the retinal thickness at non-central regions of the ETDRS grid. The effect of axial length and refractive error on retinal thickness is reduced after correcting for transverse magnification effects resulting from axial length differences.
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ItemTime spent outdoors through childhood and adolescence - assessed by 25-hydroxyvitamin D concentration - and risk of myopia at 20 years(WILEY, 2021-09)PURPOSE: To investigate the relationship between time spent outdoors, at particular ages in childhood and adolescence, and myopia status in young adulthood using serum 25-hydroxyvitamin D [25(OH)D] concentration as a biomarker of time spent outdoors. METHODS: Participants of the Raine Study Generation 2 cohort had 25(OH)D concentrations measured at the 6-, 14-, 17- and 20-year follow-ups. Participants underwent cycloplegic autorefraction at age 20 years, and myopia was defined as a mean spherical equivalent -0.50 dioptres or more myopic. Logistic regression was used to analyse the association between risk of myopia at age 20 years and age-specific 25(OH)D concentrations. Linear mixed-effects models were used to analyse trajectory of 25(OH)D concentrations from 6 to 20 years. RESULTS: After adjusting for sex, race, parental myopia, body mass index and studying status, myopia at 20 years was associated with lower 25(OH)D concentration at 20 years (per 10 nmol/L decrease, odds ratio (aOR)=1.10, 95% CI: 1.02, 1.18) and a low vitamin D status [25(OH)D < 50 nmol/L] at 17 years (aOR = 1.71, 95% CI: 1.06, 2.76) and 20 years (aOR = 1.71, 95% CI: 1.14, 2.56), compared to those without low vitamin D status. There were no associations between 25(OH)D at younger ages and myopia. Individuals who were myopic at 20 years had a 25(OH)D concentration trajectory that declined, relative to non-myopic peers, with increasing age. Differences in 25(OH)D trajectory between individuals with and without myopia were greater among non-Caucasians compared to Caucasians. CONCLUSIONS: Myopia in young adulthood was most strongly associated with recent 25(OH)D concentrations, a marker of time spent outdoors.
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ItemNo Preview AvailableOlfactory dysfunction at six months after coronavirus disease 2019 infection(CAMBRIDGE UNIV PRESS, 2021-09)OBJECTIVE: This study aimed to assess olfactory dysfunction in patients at six months after confirmed coronavirus disease 2019 infection. METHODS: Coronavirus disease 2019 positive patients were assessed six months following diagnosis. Patient data were recoded as part of the adapted International Severe Acute Respiratory and Emerging Infection Consortium Protocol. Olfactory dysfunction was assessed using the University of Pennsylvania Smell Identification Test. RESULTS: Fifty-six patients were included. At six months after coronavirus disease 2019 diagnosis, 64.3 per cent of patients (n = 36) were normosmic, 28.6 per cent (n = 16) had mild to moderate microsmia and 7 per cent (n = 4) had severe microsmia or anosmia. There was a statistically significant association between older age and olfactory dysfunction. Hospital or intensive care unit admission did not lead to worse olfactory outcomes compared to those managed in the out-patient setting. CONCLUSION: At six months after coronavirus disease 2019 diagnosis, approximately two-thirds of patients will be normosmic. This study is the first to describe six-month outcomes for post-coronavirus disease 2019 patients in terms of olfactory dysfunction.
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ItemImproving parents' knowledge of early signs of paediatric eye disease: A double-blind randomized controlled trial(WILEY, 2020-12)IMPORTANCE: Educating parents to recognize signs of eye disease and consult a healthcare professional is critical to timely diagnosis, intervention and outcomes. BACKGROUND: We evaluate the effectiveness of an eye-health information pamphlet on parents' level of concern and help-seeking intention should they hypothetically observe leukocoria or strabismus in their child. DESIGN: Double-blind, randomized controlled trial conducted at a metropolitan antenatal outpatient clinic. PARTICIPANTS: In total, 518 pregnant women were enrolled in the study. METHODS: After completing a study-specific, pre-test survey describing hypothetical clinical scenarios at baseline, participants were randomly assigned to receive a pamphlet on either paediatric eye health (intervention) or infant play (control). The post-test survey was sent by email 2 weeks after baseline. MAIN OUTCOME MEASURES: A change in the parents' level of concern if they observed leukocoria or strabismus and a change in their help-seeking intention if they hypothetically observed leukocoria or strabismus in their child. RESULTS: Of the 518 women, 382 (73.7%) completed the post-test survey. At follow-up, women who received the intervention were more likely to report a higher level of concern if they observed leukocoria (OR 1.711 [CI: 1.176-2.497] P = .005]) and were less likely to delay help-seeking (OR 0.560 [CI 0.382-0.817] P = .003). No change in the level of concern for strabismus was identified between the groups; however, at follow-up, women who received the intervention were less likely to delay help-seeking (OR 0.318 [CI 0.125-0.806] P = .016). CONCLUSION AND RELEVANCE: Providing parents with relevant, evidence-based information can significantly improve their knowledge and positively influence help-seeking intentions if leukocoria or strabismus are observed.
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ItemFunctional benefits of a chorioretinal anastomosis at 2 years in eyes with a central retinal vein occlusion treated with ranibizumab compared with ranibizumab monotherapy(BMJ PUBLISHING GROUP, 2021)OBJECTIVE: To evaluate the functional benefits (best corrected visual acuity (BCVA), central subfield thickness, injection loads, central venous pressure (CVP)) of a laser-induced chorioretinal anastomosis (L-CRA) in patients with central retinal vein occlusion (CRVO) treated with ranibizumab compared with ranibizumab monotherapy. METHODS AND ANALYSIS: This is a post-hoc analysis of the 2-year randomised ranibizumab plus L-CRA for CRVO trial. Twenty-four patients (82.5%) developed a functioning or successful L-CRA; outcome effects were monitored in the monthly as-needed ranibizumab phase from months 7 to 24 and compared with the ranibizumab monotherapy group (n=29). RESULTS: From months 7 to 24, the mean (95% CI) injection load for the functioning L-CRA group was 2.18 (1.57 to 2.78) compared with 7.07 (6.08 to 8.06) for the control group (p<0.0001). The mean BCVA was averaged across all timepoints between the control and functioning L-CRA groups (average difference=11.46 (3.16 to 19.75) letters, p=0.01). At 2 years, there was an 82.5% reduction in the odds of high CVP (greater or equal to central retinal artery diastolic pressure) for those with a successful L-CRA compared with controls (p<0.0001). CONCLUSION: For patients with CRVO, adding L-CRA as a causal-based treatment to conventional therapy reduced CVP and injection loads and offered improved BCVA.Trial registration number ACTRN12612000004864.
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ItemAssociations Between Fetal Growth Trajectories and the Development of Myopia by 20 Years of Age(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2020-12)PURPOSE: To evaluate the contribution of genetic and early life environmental factors, as reflected by fetal anthropometric growth trajectories, toward the development of myopia during childhood and adolescence. METHODS: This analysis included 498 singleton Caucasian participants from the Raine Study, a pregnancy cohort study based in Western Australia. Serial fetal biometric measurements of these participants were collected via ultrasound scans performed at 18, 24, 28, 34, and 38 weeks' gestation. At a 20-year follow-up, the participants underwent a comprehensive ophthalmic examination, including cycloplegic autorefraction and ocular biometry measurements. Using a group-based trajectory modeling approach, we identified groups of participants with similar growth trajectories based on measurements of fetal head circumference (HC), abdominal circumference, femur length (FL), and estimated fetal weight (EFW). Differences between trajectory groups with respect to prevalence of myopia, axial length (AL), and corneal radius of curvature measured at the 20-year follow-up were evaluated via logistic regression and analysis of variance. RESULTS: Prevalence of myopia was highest among participants with consistently short or consistently long FLs (P = 0.04). There was also a trend toward increased prevalence with larger HC in late gestation, although not at a statistically significant level. Trajectory groups reflecting faster HC, FL, or EFW growth correlated with significantly flatter corneas (P = 0.03, P = 0.04, and P = 0.01, respectively) and a general, but not statistically significant, increase in AL. CONCLUSIONS: Environmental or genetic factors influencing intrauterine skeletal growth may concurrently affect ocular development, with effects persisting into adulthood.
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ItemInterpreting MAIA Microperimetry Using Age- and Retinal Loci-Specific Reference Thresholds(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2020-06)PURPOSE: Macular Integrity Assessment (MAIA) microperimetry is used widely in clinical trials and routine practice to assess paracentral scotoma. Current interpretation of MAIA is based on an assumed uniform 25 decibel (dB) cutoff for normal function irrespective of subject age and retinal location. We examined this convention by establishing an age- and loci-specific reference in healthy eyes and comparing this to the <25 dB cutoff. METHODS: Retrospective MAIA results from healthy eyes were analyzed for prevalence of loci with <25 dB. At each locus, a new reference cutoff was derived from quantile regression of sensitivity against age at the 2.5th percentile. Two clinical cases of serial MAIA testing were analyzed using the new approach and compared to the <25 dB cutoff. RESULTS: Fifty-four and 56 age-matched (range: 16-75 years) healthy eyes underwent small (37 loci) and large (68 loci) grid testing, respectively. Retinal sensitivity <25 dB was found in 5% of the small grid (1998 data points) and 10% of the large grid (3808 data points). These were found predominantly in older subjects and at the central point or in the perifoveal region. Quantile regression at each individual locus showed age-related decline with a median gradient of 0.6 dB/decade. CONCLUSIONS: We caution against using <25 dB cutoff in MAIA interpretation and advocate an age- and loci-specific cutoff criterion. TRANSLATIONAL RELEVANCE: Our study suggests that MAIA interpretation is influenced by the criterion used for defining abnormal pointwise measurement.