Melbourne School of Population and Global Health - Research Publications
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ItemGrand Challenges in global eye health: a global prioritisation process using Delphi method(ELSEVIER SCI LTD, 2022-01)BACKGROUND: We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. METHODS: Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. FINDINGS: Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. INTERPRETATION: This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenges. FUNDING: The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity, National Institute for Health Research Moorfields Biomedical Research Centre, Wellcome Trust, Sightsavers, The Fred Hollows Foundation, The Seva Foundation, British Council for the Prevention of Blindness, and Christian Blind Mission. TRANSLATIONS: For the French, Spanish, Chinese, Portuguese, Arabic and Persian translations of the abstract see Supplementary Materials section.
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ItemRelationship between reticular pseudodrusen and choroidal thickness in intermediate age-related macular degeneration(WILEY, 2018-07)IMPORTANCE: Reticular pseudodrusen (RPD) is strongly associated with late age-related macular degeneration (AMD) but their aetiology remains unknown. RPD have been associated with reduced choroidal thickness (ChT) but most studies are limited by small sample size and varying severity of AMD. BACKGROUND: To investigate the relationship between choroidal thickness and RPD in eyes with intermediate AMD (iAMD), controlling for variables known to influence ChT. DESIGN: Retrospective cohort study. PARTICIPANTS: Participants were recruited from Centre for Eye Research Australia. METHODS: Colour fundus photographs, fundus auto fluorescence, near-infrared and spectral-domain ocular coherence tomography (OCT) were graded for RPD. ChT was measured from enhanced-depth imaging OCT scans at the centre of fovea, 1500 and 3000 μm nasal, temporal, superior and inferior from centre of fovea. MAIN OUTCOME MEASURES: ChT between RPD and non-RPD group. RESULTS: A total of 297 eyes from 152 subjects were included. A total of 84 (28%) had RPD and were older than non-RPD group (75.1 ± 5.4 years and 68.7 ± 6.9 years, respectively; P < 0.001). In unadjusted analysis, the RPD group was significantly associated with thinner choroids across all measured locations (P ≤ 0.022). After adjustment for variables, the presence of RPD was no longer associated with ChT (P ≥ 0.132 for all locations) but age (P < 0.001) and refractive error (P = 0.002) remained significantly associated with ChT. CONCLUSIONS AND RELEVANCE: Age and refractive error, rather than RPD, was significantly associated with reduced ChT in eyes with iAMD. Choroidal insufficiency may be a less important variable in RPD aetiology than previously considered.
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ItemPresymptomatic Retinal Sensitivity Changes in Intermediate Age-Related Macular Degeneration Associated With New Retinal Fluid(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2019-11)PURPOSE: To determine whether change in retinal sensitivity in areas with subretinal or intraretinal fluid secondary to age-related macular degeneration (AMD) precedes visual symptoms. If confirmed, retinal sensitivity testing could be used for home monitoring in AMD. METHODS: Individuals with intermediate AMD enrolled in a longitudinal study were seen every 6 months and underwent best-corrected visual acuity testing (BCVA), spectral domain-optical coherence tomography (SD-OCT), and microperimetry. Asymptomatic individuals who developed incidental, reading center-determined retinal fluid detected on SD-OCT were identified. The point-wise sensitivity (PWS) at the time of fluid detection was compared with 6 and 12 months prior. RESULTS: Fourteen of 161 individuals developed fluid without symptoms. PWS over fluid areas at detection was reduced compared with 6 (difference -2.04 dB, P < 0.001) and 12 months (-2.27 dB, P < 0.001) prior. PWS over fluid areas was reduced compared with perifluid areas (difference -1.02 dB, P = 0.03), peripheral areas (-1.51 dB, P < 0.001), nonprogressed fellow eyes (-1.49 dB, P = 0.006), and nonprogressed age-matched intermediate AMD eyes (-2.29 dB, P = 0.001). No difference in BCVA was observed in eyes developing fluid compared to eyes that do not develop fluid (P = 0.76). CONCLUSIONS: Retinal areas with fluid on SD-OCT had a corresponding reduction in retinal sensitivity at the time of fluid detection compared with 6 and 12 months prior, in asymptomatic intermediate AMD without change in BCVA. TRANSLATIONAL RELEVANCE: Development of self-monitoring tools to detect changes in retinal sensitivity may be helpful for early detection of retinal fluid suggestive of progression to neovascular AMD before acuity is affected.
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ItemProperties of the Impact of Vision Impairment and Night Vision Questionnaires Among People With Intermediate Age-Related Macular Degeneration(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2019-09)PURPOSE: To explore the psychometric properties of the Impact of Vision Impairment (IVI-28) and Night Vision Questionnaires (NVQ-10) among people with intermediate age-related macular degeneration (iAMD). METHODS: Baseline responses were collected from 288 participants (aged 50-88 years, 74% female) in the Laser intervention in Early stages of Age-related macular Degeneration (LEAD) study in Australia and Northern Ireland. Psychometric properties (discrimination, ordering of thresholds, person separation, item miss-fit, and differential item functioning according to sex) were explored using grouped rating scale and partial credit models. Spearman's correlation was estimated to assess the association with measures of visual function (mean mesopic microperimetric sensitivity, best-corrected visual acuity, low-luminance visual acuity, and low-luminance deficit). The psychometric properties were then explored following recalibration of the instruments. RESULTS: In this homogenous population, ceiling effects caused by relatively high levels of functional vision were evident for both instruments. The IVI-28 and NVQ-10 displayed suboptimal discrimination between levels of functional vision in iAMD and poor targeting among people with iAMD. The correlation between ability scores and measures of visual function was mild. In general, the NVQ-10 showed superior psychometric properties to the IVI-28 among these participants. No significant improvement in reliability could be gained following recalibration. CONCLUSIONS: Both instruments were designed for populations with more severe visual loss and poorly discriminate in this cohort of iAMD. TRANSLATIONAL RELEVANCE: New instruments that can capture the subtle changes in functional vision that occur early in AMD are required to aid evaluation of emerging interventions for iAMD.
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ItemA comparison of methods to estimate the survivor average causal effect in the presence of missing data: a simulation study (vol 19, 223, 2019)(BMC, 2020-02-27)In the original publication of this article [1], the incorrect causal diagram was submitted as Fig. 1.
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ItemA comparison of methods to estimate the survivor average causal effect in the presence of missing data: a simulation study(BMC, 2019-12-03)BACKGROUND: Attrition due to death and non-attendance are common sources of bias in studies of age-related diseases. A simulation study is presented to compare two methods for estimating the survivor average causal effect (SACE) of a binary exposure (sex-specific dietary iron intake) on a binary outcome (age-related macular degeneration, AMD) in this setting. METHODS: A dataset of 10,000 participants was simulated 1200 times under each scenario with outcome data missing dependent on measured and unmeasured covariates and survival. Scenarios differed by the magnitude and direction of effect of an unmeasured confounder on both survival and the outcome, and whether participants who died following a protective exposure would also die if they had not received the exposure (validity of the monotonicity assumption). The performance of a marginal structural model (MSM, weighting for exposure, survival and missing data) was compared to a sensitivity approach for estimating the SACE. As an illustrative example, the SACE of iron intake on AMD was estimated using data from 39,918 participants of the Melbourne Collaborative Cohort Study. RESULTS: The MSM approach tended to underestimate the true magnitude of effect when the unmeasured confounder had opposing directions of effect on survival and the outcome. Overestimation was observed when the unmeasured confounder had the same direction of effect on survival and the outcome. Violation of the monotonicity assumption did not increase bias. The estimates were similar between the MSM approach and the sensitivity approach assessed at the sensitivity parameter of 1 (assuming no survival bias). In the illustrative example, high iron intake was found to be protective of AMD (adjusted OR 0.57, 95% CI 0.40-0.82) using complete case analysis via traditional logistic regression. The adjusted SACE odds ratio did not differ substantially from the complete case estimate, ranging from 0.54 to 0.58 for each of the SACE methods. CONCLUSIONS: On average, MSMs with weighting for exposure, missing data and survival produced biased estimates of the SACE in the presence of an unmeasured survival-outcome confounder. The direction and magnitude of effect of unmeasured survival-outcome confounders should be considered when assessing exposure-outcome associations in the presence of attrition due to death.
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ItemRelationship Between Rod-Mediated Sensitivity, Low-Luminance Visual Acuity, and Night Vision Questionnaire in Age-Related Macular Degeneration(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2020-05)PURPOSE: To quantify the association between dark adaptation parameters and other clinical measures of visual function among people with and without early and intermediate age-related macular degeneration (AMD). METHODS: In this cross-sectional study, participants underwent multimodal imaging and visual function testing, including best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), low-luminance deficit (LLD = BCVA - LLVA) and the 10-item Night Vision Questionnaire (NVQ-10). Dynamic and static dark-adapted chromatic perimetry (DACP) was performed. Sensitivity difference was defined as the difference in sensitivity between the 505-nm and 625-nm stimuli. Rod intercept time (RIT) was estimated as the time required to reach a threshold of -3 log candelas/meter2 with the 505-nm stimulus following bleaching. The magnitude of association between the DACP parameters and other clinical tests was estimated via mixed-effects regression. RESULTS: A total of 51 participants (aged 51-88 years, 65% female, 39% with AMD) were included. RIT was found to be negatively associated with BCVA (P < 0.001), LLVA (P = 0.005), and NVQ-10 score (P = 0.028) but not LLD (P = 0.763). There was no evidence of an association between sensitivity difference and any of the clinical measures (P ≥ 0.081). CONCLUSIONS: Reduced rod function, as determined by RIT, was associated with lower NVQ-10 scores (designed to interrogate rod-mediated function) and with worse BCVA and LLVA (measures of cone function). TRANSLATIONAL RELEVANCE: Decreasing rod function maybe indicative of more generalized photoreceptor dysfunction involving cones. Further development of questionnaires to target function in scotopic conditions may provide an easier to administer test without the need to perform perimetric tests of rod function.
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ItemNovel measures of cardiovascular health and its association with prevalence and progression of age-related macular degeneration: the CHARM study(BMC, 2008)BACKGROUND: To determine if novel measures of cardiovascular health are associated with prevalence or progression of age-related macular degeneration (AMD). METHODS: Measures of the cardiovascular system: included intima media thickness (IMT), pulse wave velocity (PWV), systemic arterial compliance (SAC), carotid augmentation index (AI). For the prevalence study, hospital-based AMD cases and population-based age- and gender-matched controls with no signs of AMD in either eye were enrolled. For the progression component, participants with early AMD were recruited from two previous studies; cases were defined as progression in one or both eyes and controls were defined as no progression in either eye. RESULTS: 160 cases and 160 controls were included in the prevalence component. The upper two quartiles of SAC, implying good cardiovascular health, were significantly associated with increased risk of AMD (OR = 2.54, 95% CL = 1.29, 4.99). High PWV was associated with increased prevalent AMD. Progression was observed in 82 (32.3%) of the 254 subjects recruited for the progression component. Higher AI (worse cardiovascular function) was protective for AMD progression (OR = 0.30, 95%CL = 0.13, 0.69). Higher aortic PWV was associated with increased risk of AMD progression; the highest risk was seen with the second lowest velocity (OR = 6.22, 95% CL = 2.35, 16.46). CONCLUSION: The results were unexpected in that better cardiovascular health was associated with increased risk of prevalent AMD and progression. Inconsistent findings between the prevalence and progression components could be due to truly different disease etiologies or to spurious findings, as can occur with inherent biases in case control studies of prevalence. Further investigation of these non-invasive methods of characterizing the cardiovascular system should be undertaken as they may help to further elucidate the role of the cardiovascular system in the etiology of prevalent AMD and progression.
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ItemVisual Impairment as a Function of Visual Acuity in Both Eyes and Its Impact on Patient Reported Preferences(PUBLIC LIBRARY SCIENCE, 2013-12-05)PURPOSE: To assess the impact of VA loss on patient reported utilities taking both eyes into account compared to taking only the better or the worse eye into account. METHODS: In this cross-sectional study 1085 patients and 254 controls rated preferences with the generic health-related (EQ-5D; n = 868) and vision-specific (Vision and Quality of Life Index (VisQoL); n = 837) multi-attribute utility instruments (MAUIs). Utilities were calculated for three levels of VA in the better and worse eyes, as well as for 6 different vision states based on combinations of the better and worse eye VA. RESULTS: Using the VisQoL, utility scores decreased significantly with deteriorating vision in both the better and worse eyes when analysed separately. When stratified by the 6 vision states, VisQoL utilities decreased as VA declined in the worse eye despite stable VA in the better eye. Differences in VisQoL scores were statistically significant for cases where the better eye had no vision impairment and the worse seeing fellow eye had mild, moderate or severe vision impairment. In contrast, the EQ-5D failed to capture changes in better or worse eye VA, or any of the six vision states. CONCLUSIONS: Calculating utilities based only on better eye VA or using a generic MAUI is likely to underestimate the impact of vision impairment, particularly when the better eye has no or little VA loss and the worse eye is moderately to severely visually impaired. These findings have considerable implications for the assessment of overall visual impairment as well as economic evaluations within eye health.