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Work-Integrated Learning (WIL) programs play an important role in the learning experience of students in higher education and are widely used in many institutions. Within a large public research-intensive university in Australia, WIL approaches are used in many faculties, although this paper is focused on WIL within the tourism discipline. One of the capstone subjects in the undergraduate and postgraduate tourism programs utilise a WIL framework, whereby mentors assist groups of students to conduct projects for industry clients during a 13-week semester. This study aims to explore effective mentoring processes within the WIL program environment by interviewing mentors to identify their guidance and coaching experience, skills and capabilities and their self-development in this mentoring process. This study's outcome can assist to better understand the role of mentor in WIL for the design of future WIL programs. [ABSTRACT FROM AUTHOR]

This study investigates the complexity of spatial soil modelling, particularly focusing on the challenge of variable vertical support in traditional soil data collection. Traditional soil sampling, described in terms of horizons, often fails to accurately pinpoint the specific depths for specific soil properties. This gap is significant, as depth-specific data is crucial for a thorough understanding of soil formation processes and for assessing potential environmental impacts. In digital soil mapping (DSM), the prevalent reliance on standardised depth intervals and mass-preserving spline functions for data resampling results in a modelling approach that tends to disregard depth-related details, thereby introducing potential uncertainties. To address these limitations, this work explores how effectively Gaussian process regression (GPR) can model soil in 3D. This technique comprises two key components: a mean function and a semivariogram-like kernel. Unlike conventional methods that make a single prediction, GPR provides detailed probability distributions. This capability allows for the quantification of prediction uncertainty at various points, offering insights for decision-making and risk assessment purposes. Moreover, GPR has the capability to make volume or block estimates and assess associated uncertainties. Enabling volume-based predictions enriches the range of strategies available for land management. In this research, we employ GPR as a novel 3D soil modelling technique and compare its performance with traditional spline-based methods. The comparison is conducted through a case study on a farm in northern New South Wales, Australia, focusing on the 3D mapping of soil pH and electrical conductivity (EC). Our results demonstrate the ability of GPR to estimate soil properties across various volumes, utilising data from multiple vertical supports, thereby offering a more versatile approach for soil modelling in diverse spatial contexts. • Enable 3D digital soil mapping. • Account for multiple vertical support. • Produce both point and volume/block predictions. • Quantify the probability of exceedance a certain value. • Introduce an open-source GPR package. [ABSTRACT FROM AUTHOR]

• Vis-NIR libraries were set for predicting CEC and pH in Australian sugarcane soils. • The Cubist model demonstrated superior performance compared to PLSR, and SVM. • Efficient predictions were achieved by multi-depth libraries. • Minimum 300 sites (1.78 sites/ha) for accurate predictions were recommended. In sugarcane growing areas of Queensland Australia, management of soil condition requires information about soil chemical properties (i.e., cation exchange capacity [CEC], and pH), because they are used to make fertiliser recommendations. While laboratory analysis is cost prohibitive the development of visible near–infrared (Vis–NIR) spectroscopy libraries might be useful. The aims of this study was to compare: i) linear (i.e., Partial least squares regression [PLSR]) and machine learning (i.e., Cubist, Random Forest [RF] and Support vector machine [SVM]) algorithms in terms of their calibration strength (i.e., coefficient of determination (R2); ii) depth-specific (i.e., topsoil [0 – 0.3 m], subsurface [0.3 – 0.6 m], subsoil [0.6 – 0.9 m] and deep subsoil [0.9 – 1.2 m]) and multi-depth libraries; iii) prediction R2, agreement (Lin's concordance correlation coefficient [LCCC]) and accuracy (ratio of performance to interquartile [RPIQ]); and iv) minimum number of calibration sample locations (i.e., n = 400, 350, ..., 50). For depth-specific calibration for CEC, strong calibration R2 was achieved for the subsurface (i.e., RF [0.95], Cubist [0.93], PLSR [0.88] and SVM [0.81]), and for pH, the largest R2 was for deep subsoil (i.e., RF [0.91], followed by PLSR [0.80], Cubist [0.79] and SVM [0.56]), with subsurface, and deep subsoil similar, with topsoil R2 smaller. In terms of model prediction of depth-specific, Cubist was superior to PLSR, RF and SVM for CEC, and PLSR was the best for pH. For example, agreement for topsoil CEC was substantial for Cubist (0.80) and PLSR (0.80), but moderate for RF (0.69) and poor for SVM (0.59). For subsurface (0.9), subsoil (0.91) and deep subsoil (0.92), the agreements were perfect for CEC using Cubist. In terms of multi-depth calibration for CEC it was strong for RF (R2 = 0.94), Cubist (0.92), PLSR (0.81) and SVM (0.72), but for prediction agreement, Cubist (LCCC = 0.92) was perfect, with PLSR (0.85), RF (0.84) and SVM (0.83) substantial. This was also the case for pH (0.84) substantial. However, there are efficiencies in developing a multi-depth calibration. Moreover, the minimum number of calibration sample sites required was 300 (i.e., 1,200 samples) (1.78 sites/ha). The results have implications for using a Vis–NIR library to replace traditional soil laboratory analysis and for fertiliser recommendations for sugarcane soil. [ABSTRACT FROM AUTHOR]

To assess contributions of dietary and genetic factors to ethnic differences in AMD prevalence. Population-based analytical study. In the Blue Mountains Eye Study, Australia (European ancestry n = 2826) and Multi-Ethnic Cohort Study, Singapore (Asian ancestry, n = 1900), AMD was assessed from retinal photographs. Patterns of dietary composition and scores of the Alternative Healthy Eating Index were computed using food frequency questionnaire data. Genetic susceptibility to AMD was determined using either single nucleotide polymorphisms (SNPs) of the complement factor H and age-related maculopathy susceptibility 2 genes, or combined odds-weighted genetic risk scores of 24 AMD-associated SNPs. Associations of AMD with ethnicity, diet, and genetics were assessed using logistic regression. Six potential mediators covering genetic, diet and lifestyle factors were assessed for their contributions to AMD risk difference between the two samples using mediation analyses. Age-standardized prevalence of any (early or late) AMD was higher in the European (16%) compared to Asian samples (9%, p <.01). Mean AMD-related genetic risk scores were also higher in European (33.3 ± 4.4) than Asian (Chinese) samples (31.7 ± 3.7, p <.001). In a model simultaneously adjusting for age, ethnicity, genetic susceptibility and Alternative Healthy Eating Index scores, only age and genetic susceptibility were significantly associated with AMD. Genetic risk scores contributed 19% of AMD risk difference between the two samples while intake of polyunsaturated fatty acids contributed 7.2%. Genetic susceptibility to AMD was higher in European compared to Chinese samples and explained more of the AMD risk difference between the two samples than the dietary factors investigated. [ABSTRACT FROM AUTHOR]

The present study aims to investigate the effect of wholegrain and legume consumption on the incidence of age-related cataract in an older Australian population-based cohort. The Blue Mountains Eye Study (BMES) is a population-based cohort study of eye diseases among older adults aged 49 years or older (1992–1994, n 3654). Of 2334 participants of the second examination of the BMES (BMES 2, 1997–2000), 1541 (78·3 % of survivors) were examined 5 years later (BMES 3) who had wholegrain and legume consumption estimated from the FFQ at BMES 2. Cataract was assessed using photographs taken during examinations following the Wisconsin cataract grading system. Multivariable-adjusted logistic regression models were used to assess associations with the 5-year incidence of cataract from BMES 2 (baseline) to BMES 3. The 5-year incidence of cortical, nuclear and posterior subcapsular (PSC) cataract was 18·2, 16·5 and 5·9 %, respectively. After adjustment for age, sex and other factors, total wholegrain consumption at baseline was not associated with incidence of any type of cataract. High consumption of legumes showed a protective association for incident PSC cataract (5th quintile: adjusted OR 0·37; 95 % CI 0·15, 0·92). There was no significant trend of this association across quintiles (P = 0·08). In this older Australian population, we found no associations between wholegrain intake at baseline and the 5-year incidence of three cataract types. However, intake of legumes in the highest quintile, compared with the lowest quintile, may protect against PSC formation, a finding needing replication in other studies. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to examine the relationships of food security and diet quality with health related quality of life (HRQoL) in a cohort of older Australians. Methods: Data were collected as part of the Blue Mountains Eye Study, a cohort study of community ‐ living individuals aged 49 years and over. A 12 ‐ item food security survey, the Short ‐ form 36 ‐ item (SF ‐ 36) health survey, assessing four physical and four mental domains of HRQoL, and a food frequency questionnaire (FFQ) were completed by 2642 participants. The Total Diet Score (TDS) (maximum score 20) measured diet quality based on food intake from the FFQ. Analysis of covariance compared adjusted mean differences in SF ‐ 36 scores between (i) food secure and food insecure groups and; (ii) quartiles of TDS. Higher SF ‐ 36 scores indicated better physical and mental health. Results: Across all SF ‐ 36, domains scores were significantly lower in the food insecure group compared to the food secure group. Adjusted mean differences ranged from 4.01 (95% confidence intervals (CIs): 1.64, 6.38) to 18.00 (95% CIs: 13.43, 22.56). Individuals in the lowest quartile of TDS had significantly lower SF ‐ 36 scores compared to those in the highest TDS quartile for physical functioning domain (4.46, 95% CIs: 1.67, 7.26) and vitality domain (4.14, 95% CIs: 1.34, 6.95). Conclusions: The study findings provide evidence of associations between reduced physical and mental health and food insecurity and poor diet quality, respectively. Further research into food insecurity in the ageing population is required to ensure that good health is maintained through appropriate health and community services. [ABSTRACT FROM AUTHOR]

Congenital cataract is the most common cause of treatable visual impairment in children worldwide. Mutations in many different genes lead to congenital cataract. Recently, mutations in the receptor tyrosine kinase gene, EPHA2, have been found to cause congenital cataract in six different families. Although these findings have established EPHA2 as a causative gene, the total contribution of mutations in this gene to congenital cataract is unknown. In this study, for the first time, a population-based approach was used to investigate the frequency of disease causing mutations in the EPHA2 gene in inherited cataract cases in South-Eastern Australia. A cohort of 84 familial congenital or juvenile cataract index cases was screened for mutations in the EPHA2 gene by direct sequencing. Novel changes were assessed for segregation with the disease within the family and in unrelated controls. Microsatellite marker analysis was performed to establish any relationship between families carrying the same mutation. We report a novel congenital cataract causing mutation c.1751C>T in the EPHA2 gene and the previously reported splice mutation c.2826-9G>A in two new families. Additionally, we report a rare variant rs139787163 potentially associated with increased susceptibility to cataract. Thus mutations in EPHA2 account for 4.7% of inherited cataract cases in South-Eastern Australia. Interestingly, the identified rare variant provides a link between congenital and age-related cataract. [ABSTRACT FROM AUTHOR]

Abstract: Crisis planning is an important strategy for developing more resilient tourism organisations. Given this, it is important to examine how managers perceive crisis planning because managers’ attitudes and perceptions may affect behavioural intentions. The objective of this study, then, is to identify the attitudes and perceptions of crisis planning behaviour held by managers in the accommodation sector in Australia, and to analyse the relationships between the belief-based measures (behavioural, normative and control beliefs), direct measures (attitudes, subjective norms, and perceived behavioural control), and behavioural intentions. At the first stage, semi-structured interviews were conducted with nine managers to discover the perceived advantages and disadvantages for implementing crisis planning, the most important people who would approve or disapprove of implementing crisis planning, and what facilitating factors or barriers managers thought could make it easier or more difficult to adopt the behaviour. At the second stage, managers (N =386) in the accommodation sector completed a questionnaire applying the theory of planned behaviour. Intentions to undertake crisis planning were predicted from attitudes and subjective norms (R =.51; p <.01). Attitudes were related to beliefs about short- and long-term benefits as well as disadvantages of crisis planning; subjective norms reflected expectations of owners, stakeholders, colleagues and guests; and control considerations which included time, money, equipment, consultants and procedures. This information can assist in the preparation of effective intervention strategies. The findings of this study provide valuable guidance for researchers and practitioners for identifying the mechanisms to improve the crisis preparedness of organisations. [Copyright &y& Elsevier]

Abstract: Despite the potential of crisis planning and preparedness to create more resilient tourism organisations, the majority of past studies concerned with tourism crises have focused on response and recovery, rather than on crisis planning. Further, most are descriptive in nature and few have undertaken a predictive or explanatory research approach underpinned by a strong theoretical framework. This study attempts to provide a deeper understanding of the psychological factors that influence crisis planning in the Australian accommodation industry. The theory of planning behaviour (TPB) was extended to examine the influence of attitudes, social norms, perceived behavioural control and past experience on crisis planning intentions. Data were collected through a nationwide online survey in Australia (N =386) and analysed by path analysis using structural equation modelling. In terms of predicting crisis planning intentions, three individual psychological factors (attitude, subjective norms, and past crisis experience) were identified as the key factors that influence crisis planning behaviour, while the path coefficient between perceived control and behavioural intentions was not found to be significant. These findings suggest that managers and industry associations should articulate the advantages of crisis planning and provide resources, tool kits, and workshops to support attitude change and boost reference group support. These findings will also be of interest to tourism sectors other than the accommodation industry, and to countries other than Australia. Future research avenues based on the findings are also outlined. [Copyright &y& Elsevier]

Background: Higher intake of carbohydrates and high-glycemic index (high-GI) diets could lead to small vessel dysfunction. Objectives: We aimed to assess the associations between intakes of high-GI and high-glycemic load (high-GL) diets, carbohydrate, and the main carbohydrate-containing food groups and retinal microvascular changes in preadolescents. Design: Students aged 12 y (n = 2353) from a random cluster sample of 21 schools underwent detailed eye examinations. Retinal vessel caliber and fractal dimension were measured from digital retinal images. A validated semiquantitative food-frequency questionnaire was administered. Results: After multivariable adjustment, children who consumed soft drinks once or more per day had significantly narrower mean retinal arterioles (-1.9 µm) than did those who never or rarely consumed soft drinks (P-trend = 0.03). When the highest to lowest tertiles of carbohydrate consumption were compared, girls had significantly narrower retinal arterioles (~1.4 µm; P-trend = 0.03), and boys had wider venules (-2.3 µm; P-trend = 0.02). In girls only, a higher-GI diet was associated with narrower retinal arterioles (0.98-//m narrowing of retinal arteriolar caliber per SD increase in GI, P = 0.01). Carbohydrate intake and a high-GL diet were associated with greater retinal fractal dimension in girls (highest compared with lowest tertiles: P-trend = 0.003 and 0.01, respectively). Conclusions: Greater consumption of carbohydrates and soft drinks was associated with retinal arteriolar narrowing and venular widening. Because these microvascular signs have been shown to be markers of future cardiovascular disease risk, the presence of this risk factor in children could support the need for healthy dietary patterns that include lower consumption of high-GI foods and soft drinks. [ABSTRACT FROM AUTHOR]

Background: Cataract surgery is the most frequently performed ophthalmic procedure worldwide. While benefits gained from cataract surgery outweigh surgical risks, there have been concerns that older persons may have an increased risk of developing age-related macular degeneration (AMD) after cataract surgery. Objective: The Australian Prospective Study of Cataract Surgery and Age-Related Macular Degeneration Study aims to assess the risk of AMD in a large cohort of older patients following cataract surgery. The current report describes the study rationale, design and methodology. Design: Longitudinal studyParticipants: Approximately 2000 cataract surgical patients aged 65 years or older are being recruited from both public and private sources in western Sydney, Australia.Methods: At study visits, participants are interviewed using standardized questionnaires to obtain information on demographic, medical, and ocular conditions and AMD risk factors, together with data on general health and vision-related quality of life. Eye examinations include visual acuity, intraocular pressure, keratometry and A-scan measurements, plus lens and retinal photography, following pupil dilatation. Retinal photographs taken before cataract surgery, and at 1, 6, 12, and 24 months after surgery are graded for early and late AMD lesions, using the Wisconsin age-related maculopathy grading system. The 1-month post-operative retinal photographs supplement the baseline macular assessment for cases in which cataract occludes a clear view of the macula pre-operatively. It is intended that study participants will be followed for up to five years post-operatively to clarify the question of whether aphakic or pseudophakic, compared to phakic eyes, have a greater risk of developing AMD. [ABSTRACT FROM AUTHOR]

Purpose : To assess temporal associations between vision and self-rated health. Methods : We examined 3654 Australian residents (82.4% response) aged 49+ years in the Blue Mountains Eye Study, during 1992 to 1994, and re-examined 2334 in 1997 to 1999. Change in vision was defined if baseline and 5-year visual acuity (VA) changed by =10 letters (2 lines). Change in self-rated health was defined if overall health ranking (excellent, good, fair, poor) changed by =1 step. Results : Of 2285 participants with data from both examinations, 59.8%, 23.9%, and 16.3% reported unchanged, declined, and improved self-rated health, respectively. Among persons whose self-rated health declined, the proportions with a decline in presenting VA, no change, or improvement were similar (25.2%, 23.8% and 22.5%, respectively, p for trend = 0.5). Among participants with decline, no change, or improvement in self-rated health, a similar magnitude in the age-sex adjusted mean VA decline (-1.0 to -2.7 letters) was observed. After adjusting for age, sex, hospitalizations, and incident chronic conditions, declining VA was not associated with increased decline in 5-year self-rated health (multivariate-adjusted odds ratio 0.99, 95% CI 0.75–1.30). Conclusion : There were no parallel 5-year changes in self-rated health and vision in this population. [ABSTRACT FROM AUTHOR]

Abstract This report aims to describe the frequency of different patterns of visual field loss in open-angle glaucoma (OAG). The Blue Mountains Eye Study examined 3654 persons (aged 49+) during 1992-1994. Humphrey supra-threshold visual fields were performed in 88.9%. Those classified as glaucoma suspects had 30-2 full-threshold fields (9.2%). Of OAG cases (n = 108) with field tests in both eyes (n = 97), unilateral defects were present in 49 (50.5%) and bilateral in 48 (49.5%). Advanced field loss was found in 16 (15.4%) subjects and in 22 (10.9%) eyes, with bilateral loss present in 6 (6.2%) cases. Of all eyes of OAG cases (n = 201), 49 (24.4%) had no defects, 52 (25.9%) upper, 61 (30.3%) lower, and 17 (8.5%) had combined upper and lower loss. Of the upper and lower cases (n = 113), the types of defects included nasal step (36), arcuate (26), nasal plus arcuate (26), and hemispherical defects (25). Of subjects with fields in at least one eye (n = 104), there was a similar proportion in the worse eye of upper defects (28.8%), lower (31.7%), and combined upper and lower (24.0%). Undiagnosed OAG was more frequent in unilateral (65.3%) than bilateral (34.7%) cases (P = 0.003). This study reports the pattern of typical glaucomatous field loss in an older Australian population. [ABSTRACT FROM AUTHOR]

Abstract This study aimed to estimate the number of Australians over 50 with cataract in the years 2001 and 2021. Data from two population-based studies were pooled: the Blue Mountains Eye Study and Melbourne Visual Impairment Project and Australian Bureau of Statistics population projections were used. Similar definitions for the three cataract types were used in the two studies (nuclear ≥ grade 4, posterior sub­capsular ≥ 1 mm, cortical ≥ 10% lens area or ≥ 25% circumference). Combining the three types and prior surgery, it was estimated that in 2001, 1.7 million Australians had clinically significant cataract in either eye and 320 000 had previously undergone cataract surgery. It was estimated that the number of persons with cataract will rise to 2.7 million by 2021 (over 500 000 will have had cataract surgery). The number of Australians with cataract will grow by two-thirds during the next 20 years, reflecting continued population ageing. Health care delivery systems will need to develop methods to handle this increased workload. [ABSTRACT FROM AUTHOR]

Abstract This report describes the prevalence of self-reported dry eye syndrome and associations with systemic and ocular factors in an older Australian population. Participants of the Extension Blue Mountains Eye Study, aged 50 or older (mean age 60.8 years, n = 1174) completed a comprehensive eye examination and dry eye questionnaire. At least one dry eye symptom was reported by 57.5% of participants, with 16.6% reporting moderate to severe symptoms, more frequent in women (age-adjusted odds ratio [OR] 1.5, 95% confidence interval [CI] 1.1-2.2). Three or more symptoms were reported by 15.3% of participants, also more frequent in women (age-adjusted OR 1.7, CI 1.2-2.4). No age-related trends or significant ocular associations were observed. After adjusting for age and sex, systemic factors significantly associated with dry eye syndrome included history of arthritis, asthma, gout, use of corticosteroids, antidepressants and hormone replacement therapy. In this older population, dry eye syndrome was common and has associations with female gender and systemic diseases. [ABSTRACT FROM AUTHOR]

Objective: To quantify the relationship between pseudoexfoliation (PXF) and open-angle glaucoma, ocular hypertension, and intraocular pressure (IOP) in a defined older population. Methods: A cross-sectional study of 3654 people aged 49 to 97 years identified subjects with PXF during slitlamp examination. The IOP was measured by applanation tonometry. Glaucoma was diagnosed from characteristic visual field loss combined with optic disc cupping and rim thinning, without reference to IOP. Ocular hypertension was diagnosed if lOP was greater than 21 mm Hg in either eye, without field and disc changes. General estimating equation models were used to assess associations between eyes with PXF and glaucoma or ocular hypertension. Results: Pseudoexfoliation was diagnosed in 2.3% of subjects, and both prevalence and bilaterality increased with age. Glaucomatous damage was present in 14.2% of eyes with PXF compared with 1.7% of eyes without PXF (age- and sex-adjusted odds ratio (OR), 5.0; 95% confidence interval (CI), 2.6-9.6). This was almost unchanged (OR, 4.8) after adjustment for glaucoma risk factors and was also relatively unaffected by lOP adjustment (OR, 3.7; 95% CI, 1.8-7.6). For subjects with PXF, the relationship with glaucoma persisted, but was weaker (OR, 2.3; 95% CI, 1.0-5.0) in the multivariate model. However, the population attributable risk from PXF was only 2.7%. Ocular hypertension was also more frequent in eyes with PXF (9.3%) than in eyes without PXF (3.1%) but was of borderline significance in the multivariate model (OR, 2.3; 95% CI, 0.9-5.7). Conclusions: This study confirmed the strong relationship between glaucoma and PXF. Subjects with PXF had an increased risk of glaucoma, while eyes with PXF had a higher risk, which was independent of other glaucoma risk factors, including IOP. [ABSTRACT FROM AUTHOR]

Changes in retinal vascular caliber may reflect subclinical microvascular disease and provide prognostic information regarding risk of retinopathy. In this study, we examined the prospective association of retinal vascular caliber with retinopathy risk in an Australian population-based cohort. A total of 906 participants without retinopathy at baseline had retinal vascular caliber measured from photographs and were followed-up for 5 years for incident retinopathy. After adjusting for age, sex, systolic blood pressure, A1C, and other risk factors, individuals with wider retinal arteriolar caliber (widest 25% vs. the remaining three-quarters of the population) were more likely to develop incident retinopathy (odds ratio 4.79 [95% CI 1.57-14.58]). This association was not significant in individuals without diabetes. Venular caliber did not predict incident retinopathy. Our findings suggest that retinal arteriolar dilatation is a specific sign of diabetic microvascular dysfunction and may be a preclinical marker of diabetic retinopathy. [ABSTRACT FROM AUTHOR]

• Vis-NIR spectroscopy as cheaper and quicker measurement tool for exch. Ca and Mg. • Best exch. cations prediction in the topsoil with the PLSR. • Spiking improved the applicability of topsoil Vis-NIR library. • Cubist performed better than PLSR when soil variety was increased. • A profile library achieved equivalent results to topsoil library with spiking. Due to high rate of nutrient removal by cotton plants, the productive cotton-growing soils of Australia are becoming depleted of exchangeable (exch.) cations. For long-term development, data on exch. calcium (Ca), magnesium (Mg), potassium (K) and sodium (Na) throughout the soil profile is required. However, traditional laboratory analysis is tedious. The visible-near-infrared (Vis-NIR) spectroscopy is an alternative; whereby, spectral libraries are built which couple soil data and Vis-NIR spectra using models. While various models have been used to predict exch. cations, their performance was seldom systematically compared. Moreover, most previous studies have focused on prediction of topsoil (0–0.3 m) exch. cations while the effects of depth on applicability of topsoil spectral libraries are rarely investigated. Our first aim was to determine which model (i.e. partial least squares regression (PLSR), Cubist, random forest (RF), or support vector machine regression (SVMR)) produces the best prediction of topsoil exch. Ca, Mg, K and Na. The second aim was to evaluate if the best topsoil model can be used to predict subsurface (0.3–0.6 m) and subsoil (0.9–1.2 m) exch. cations. The third aim was to explore the effect of spiking on the prediction in subsurface and subsoil using the topsoil spectral library. The fourth aim was to see if combining all depths to build a profile spectral library improved prediction. Based on independent validation, PLSR was superior for topsoil exch. cations prediction, while Cubist outperformed PLSR in some cases when spiking was applied, and the profile spectral library was considered. Topsoil PLSR could be applied to predict exch. Ca and Mg in the subsurface and subsoil, while spiking improved prediction. Moreover, a profile spectral library achieved equivalent results with when topsoil samples coupled with spiking were considered. We, therefore, recommended to predict exch. Ca and Mg throughout the profile using topsoil spectral library coupled with spiking approach. [ABSTRACT FROM AUTHOR]

Purpose: To assess the 15-year incidence and progression of reticular drusen and associations of this lesion with age-related macular degeneration (AMD) risk factors. Design: Population-based cohort. Participants: Blue Mountains Eye Study participants (n = 3654) 49 years of age and older attended baseline examinations; of these, 75.8%, 76.7%, and 56.1% of survivors attended 5-year, 10-year, and 15-year follow-up examinations, respectively. Methods: Color retinal photographs were obtained and comprehensive questionnaires were administered at each visit, and DNA samples were genotyped. Fundus autofluorescence images were not available. Reticular drusen identified from photographs were confirmed with side-by-side grading using the Wisconsin AMD grading protocol. Incidence was assessed using Kaplan-Meier product limit survival methods, controlling for competing risk of death. Associations between smoking, fish consumption, serum lipids, systemic and dietary factors, the CFH single nucleotide polymorphism (SNP) rs1061170 and ARMS2 SNP rs10490924, and the 15-year incidence of reticular drusen were analyzed in discrete logistic regression models. Generalized estimating equation models were used to analyze eye-specific relationships between these risk factors and 5-year progression from reticular drusen to late AMD. Main Outcome Measures: Incidence and progression of reticular drusen. Results: The 15-year cumulative incidence of reticular drusen was 4.0% (n = 95). Increasing age (per decade increase; odds ratio [OR], 3.4; 95% confidence interval [CI], 2.6–4.4), female sex (OR, 2.0; 95% CI, 1.3–3.2), and presence of risk alleles of CFH-rs1061170 (OR, 1.8; 95% CI, 1.3–2.4) or ARMS2-rs10490924 (OR, 3.0; 95% CI, 2.1–4.4) were associated with higher reticular drusen incidence. Current smoking at baseline predicted higher reticular drusen incidence (OR 2.1, 95% CI 1.0–4.5) after adjusting for age, sex, CFH-rs1061170 and ARMS2-rs10490924 polymorphisms. Of 118 eyes with reticular drusen, 40 (33.9%) developed late AMD over 5 years. A higher proportion of eyes with reticular drusen located outside versus within the macular area progressed to late AMD (50.0% vs. 37.8%). Dietary lutein–zeaxanthin intake was associated with decreased likelihood of progression from reticular drusen to late AMD (adjusted OR, 0.5; 95% CI, 0.3–1.0). Conclusions: Known AMD risk factors were associated with greater long-term risk of reticular drusen. Neither total area nor central location of reticular drusen predicted 5-year progression to late AMD. Increased consumption of lutein–zeaxanthin predicted a lower risk of progression. [ABSTRACT FROM AUTHOR]

Purpose: To report prevalence and 5-year incidence of dual sensory impairment (DSI), and associated risk factors, in an older population. Methods: We included 2015 Blue Mountains Hearing Study participants aged ≥55 years, examined between 1997 and 1999 (baseline) and 2002 and 2004. Hearing thresholds were measured with the use of pure-tone audiometry. Visual acuity was measured with a LogMar chart while the subject wore distance glasses, if they owned a pair. DSI was defined as combined presenting visual acuity (better eye) <20/40, and PTA0.5–4kHz (better ear) >25 dB HL. The incidence of DSI was considered by the use of two at-risk subpopulations: (i) participants with no sensory impairment and; (ii) with one type of sensory impairment at baseline. Results: The prevalence of DSI was 6% at baseline, increasing from 0% for ages <60 years to 26.8% for ages 80+ years (p for trend <.0001). Five-year DSI incidence was1.6% in persons with no sensory impairment and 11.3% in those with a single sensory impairment, a 7-fold difference. Among participants with either no sensory impairment or a single sensory impairment at baseline, a significant age-related increase in incident DSI was found (p for trend <.0001 and .0004, respectively). Low education was a significant risk factor for DSI among those with no sensory impairment and those with single sensory impairment, multivariable-adjusted odds ratio (OR, 6.62; 95% confidence interval [95% CI], 1.79–24.4) and OR, 2.55 (95% CI, 1.36–4.79), respectively. Conclusions: Aging population trends and the age-related prevalence and incidence of DSI support the implementation of collaborative efforts in service provision between hearing and vision professionals. Active case-finding among older persons with single-sensory impairments may help identify those with DSI and provide timely and appropriate services. [Copyright &y& Elsevier]

Objective: To assess whether phacoemulsification cataract surgery exacerbates the development and progression of diabetic retinopathy (DR) in a cataract surgical cohort. Design: Clinic-based cohort study. Participants: Patients aged 65+ years undergoing cataract surgery at an eye clinic in Sydney, Australia, between 2004 and 2006. Methods: Digital retinal photography was performed after pupil dilation preoperatively and at 1-, 6-, and 12-month postoperative visits. DR was assessed using the modified Early Treatment Diabetic Retinopathy Study (ETDRS) classification. Preoperative and 1-month postoperative (baseline) photographs were compared side-by-side with 12-month postoperative photographs. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for DR progression in operated (pseudophakic) compared with nonoperated (phakic) eyes, adjusted for age, sex, diabetes duration, and preoperative glycosylated hemoglobin level. Main Outcome Measures: Incident DR was defined in eyes without DR at baseline in which DR was detected at 12-month postoperative visits. DR progression was defined as an increase of 1 or more ETDRS steps during the same period, including incident cases. Results: Of 1994 surgical patients recruited, 190 (9.53%) with diabetes and complete data and thus were included. There were 56 patients with unilateral surgery performed before baseline (mean postoperative duration 3.3±3.3 years). The prevalence of DR at baseline was higher in these 56 pseudophakic eyes than in 324 phakic eyes (71.4% vs. 48.2%, respectively, adjusted OR 2.16; 95% CI, 1.16–4.03). Of the 190 patients, 169 were followed for 12+ months postoperatively; 278 eyes were pseudophakic, and 60 eyes remained phakic at 12 months. During the 12-month postoperative period, incident DR developed in 28.2% of pseudophakic eyes and 13.8% of phakic eyes (adjusted OR 2.65; 95% CI, 1.06–6.61). In a paired-eye comparison of 45 patients who remained unilaterally pseudophakic at 12 months and were at risk of DR progression, 35.6% of pseudophakic eyes exhibited DR progression compared with 20.0% of the fellow phakic eyes (adjusted OR 2.21; 95% CI, 0.85–5.71). Conclusions: Diabetic patients undergoing phacoemulsification cataract surgery appear to have a doubling of DR progression rates 12 months after surgery. This outcome, however, represents less progression than was previously documented with intracapsular and extracapsular cataract surgical techniques. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. [Copyright &y& Elsevier]

: PurposeTo describe the 5-year cumulative incidence and change in epiretinal membranes in a defined older Australian population.: DesignPopulation-based cohort study.: ParticipantsThree thousand six hundred fifty-four persons 49 years of age or older, living in the Blue Mountains area, west of Sydney, Australia, participated in the baseline survey during 1992 to 1994. The cohort was reexamined after 5 years in 1997 to 1999. Excluding persons (543) who died since the baseline, 75% of survivors (n = 2335) attended the follow-up examination.: MethodsAll participants underwent a detailed eye examination, including stereo retinal photography. Epiretinal membranes were diagnosed from grading of baseline and 5-year retinal photographs.: Main outcome measuresEpiretinal membranes were classified as either preretinal macular fibrosis (PMF), with retinal folds, or as a less severe form, termed cellophane macular reflex (CMR), without retinal folds. The incidence of epiretinal membranes was determined if either lesion was found in eyes with no preexisting epiretinal membrane at baseline. Progression was defined if the area of involvement increased by more than 25%, regression if it decreased by more than 25%, and stable if it changed by less than 25%.: ResultsEpiretinal membranes developed in the first eye of 108 of 2030 participants who had no sign of this condition in either eye at baseline, 5.3%, 95% confidence interval (CI) 4.4 to 6.4. Five-year cumulative incidence rates for PMF and CMR were 1.5% and 3.8%, respectively. Of those participants with epiretinal membranes in one eye at baseline, 18 of 133 (13.5%) developed this sign in their second eye after 5 years. New epiretinal membranes (mostly CMR) occurred in 15 of 165 subjects (9.1%; CI, 5.2–14.6) who had undergone cataract surgery since the Blue Mountains Eye Study I. This rate was significantly higher than in the nonsurgical group, 92 of 1861 (4.9%; CI, 4.0–6.0) of whom developed epiretinal membranes. Progression from CMR to PMF was observed in 17 of 183 eyes (9.3%). Existing epiretinal membranes progressed, regressed, or remained stable in 28.6%, 25.7%, and 38.8% of eyes, respectively.: ConclusionsThis study has documented the 5-year cumulative incidence and the natural history of epiretinal membranes in an older population. [Copyright &y& Elsevier]

Objective: To summarize the prevalence of retinal vein occlusion (RVO) from studies in the United States, Europe, Asia, and Australia. Design: Pooled analysis using individual population-based data. Participants: Individual participant data from population-based studies around the world that had ascertained RVO from fundus photographs. Methods: Each study provided data on branch RVO and central RVO by age, sex, and ethnicity. Prevalence rates were directly age and sex standardized to the 2008 world population aged 30 years and older. Estimates were calculated by study and, after pooling, by ethnicity. Summary estimates included studies in which RVO was assessed from fundus photographs on ≥2 fields of both eyes. Main Outcome Measures: Any RVO, CRVO, or BRVO. Results: The combined pooled data contained 68,751 individuals from 15 studies, with participants'' ages ranging from 30 to 101 years. In analyses of 11 studies that assessed ≥2 fundus fields of both eyes (n=49,869), the age- and sex-standardized prevalence was 5.20 per 1000 (confidence interval [CI], 4.40–5.99) for any RVO, 4.42 per 1000 (CI, 3.65–5.19) for BRVO, and 0.80 per 1000 (CI, 0.61–0.99) for CRVO. Prevalence varied by race/ethnicity and increased with age, but did not differ by gender. The age- and sex-standardized prevalence of any RVO was 3.7 per 1000 (CI, 2.8–4.6) in whites (5 studies), 3.9 per 1000 (CI, 1.8–6.0) in blacks (1 study), 5.7 per 1000 (CI, 4.5–6.8) in Asians (6 studies), and 6.9 per 1000 (CI, 5.7–8.3) in Hispanics (3 studies). Prevalence for CRVO was lower than BRVO in all ethnic populations. On the basis of these data, an estimated 16.4 million (CI, 13.9–18.9) adults are affected by RVO, with 2.5 million (CI, 1.9–3.1) affected by CRVO and 13.9 million (CI, 11.5–16.4) affected by BRVO. Study limitations include non-uniform sampling frames in identifying study participants and in acquisition and grading of RVO data. Conclusions: Our study provides summary data on the prevalence of RVO and suggests that approximately 16 million people may have this condition. Research on preventive and treatment strategies for this sight-threatening eye disease is needed. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Purpose: This study conducted a bibliometric analysis of the literature on circadian rhythms and sports to identify research trends, knowledge gaps, and future directions., Methods: A total of 301 manuscripts, including 245 articles and 56 reviews, were extracted from the Web of Science Core Collection (WoSCC) database, and the bibliometric analysis was performed using VOSviewer 1.6.16., Results: The analysis revealed a continuous increase in the volume of literature on circadian rhythms and sports over the past 38 years, with a focus on the effects of circadian rhythms on physical performance, sleep quality, and jet lag. The study identified 1107 authors who have contributed to this field, with the highest number of publications from Reilly T, Chtourou H, and Atkinson G. The publications were from 512 institutions in 59 countries/regions, with Liverpool John Moores University, University of Sfax, and Manouba University being the leading institutions. The USA, UK, and Australia had the largest number of publications. The top 3 journals were Chronobiology International, Biological Rhythm Research, and Sports Medicine., Conclusion: Despite the increase in research, there are still several underexplored areas, such as the effects of circadian rhythms on cognitive and emotional processes in sports, the role of individual differences in circadian rhythms on sports outcomes, and the potential applications of circadian interventions for sports performance optimization. Future research should address these gaps to advance our understanding of the complex relationship between circadian rhythms and sports., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Calcium (Ca) and magnesium (Mg) are essential for growth of sugarcane leaves and roots, as well as respiration and nitrogen metabolism, respectively. To assist farmers decide suitable application rates of lime and Mg fertiliser, respectively, the Australian sugarcane industry established the Six-Easy-Steps nutrient management guidelines based on topsoil (0-0.3 m) Ca (cmol(+) kg -1 ) and Mg (cmol(+) kg -1 ). Given the heterogeneous nature of soil, digital soil mapping (DSM) methods can be employed to allow for the precise application rate to be determined. In this study, we examine statistical models (i.e., ordinary kriging [OK], linear mixed model [LMM], quantile regression forests [QRF], support vector machine [SVM], and Cubist regression kriging [CubistRK]) to predict topsoil and subsoil (0.6-0.9) Ca and Mg, employing digital data in combination (i.e., proximal sensing electromagnetic induction (EMI) [e.g., 1mPcon, 1mHcon, etc.], gamma-ray [γ-ray] spectrometry [i.e., TC, K, U and Th] and digital elevation model [DEM] derivatives). We also investigate various sampling designs (i.e., spatial coverage [SCS], feature space coverage [FSCS], conditioned Latin hypercube [cLHS] and simple random sampling [SRS]) and calibration sample size (i.e., n = 180, 150, 120, 90, 60 and 30). The predictions are assessed using Lin's concordance correlation coefficient (LCCC) and ratio of performance to interquartile distance (RPIQ) with an independent validation dataset (i.e., n = 40). The best results were for prediction of subsoil Mg, utilising CubistRK (LCCC = 0.82) with the largest calibration sample size (n = 180), followed by LMM (0.79), SVM (0.76), QRF (0.70) and OK (0.65). This was generally the case for topsoil and subsoil Ca. We also conclude that no single sampling design was universally better, and 180 samples were necessary for predicting topsoil Ca and Mg with moderate agreement (0.65 < LCCC < 0.80). However, with FSCS, a minimum of 120 samples were enough to calibrate a CubistRK model and achieve substantial (LCCC > 0.80) agreement for predicting subsoil Ca and Mg. With respect to soil use and management according to the Six-Easy-Steps, the sandy soil in the north and south require large application rate of lime (3.5 t/ha) and Mg (125 kg/ha), respectively. Conversely, varying amounts of fertiliser rates of lime (2.0, 1.5 and 1 t/ha) and Mg (50 kg/ha) were recommended where Vertosols were previously mapped., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease.

Background: Myopia prevalence has increased in the past 20 years, with many studies linking the increase to reduced time spent outdoors. A number of recent observational studies have shown an inverse association between vitamin D [25(OH)D] serum levels and myopia. However, in such studies it is difficult to separate the effects of time outdoors and vitamin D levels. In this work we use Mendelian randomization (MR) to assess if genetically determined 25(OH)D levels contribute to the degree of myopia., Methods: We performed MR using results from a meta-analysis of refractive error (RE) genome-wide association study (GWAS) that included 37 382 and 8 376 adult participants of European and Asian ancestry, respectively, published by the Consortium for Refractive Error And Myopia (CREAM). We used single nucleotide polymorphisms (SNPs) in the DHCR7, CYP2R1, GC and CYP24A1 genes with known effects on 25(OH)D concentration as instrumental variables (IV). We estimated the effect of 25(OH)D on myopia level using a Wald-type ratio estimator based on the effect estimates from the CREAM GWAS., Results: Using the combined effect attributed to the four SNPs, the estimate for the effect of 25(OH)D on refractive error was -0.02 [95% confidence interval (CI) -0.09, 0.04] dioptres (D) per 10 nmol/l increase in 25(OH)D concentration in Caucasians and 0.01 (95% CI -0.17, 0.19) D per 10 nmol/l increase in Asians., Conclusions: The tight confidence intervals on our estimates suggest the true contribution of vitamin D levels to degree of myopia is very small and indistinguishable from zero. Previous findings from observational studies linking vitamin D levels to myopia were likely attributable to the effects of confounding by time spent outdoors., (© The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association)

Purpose: Most classification systems for age-related macular degeneration (AMD) were developed from patients in clinical trials. We aimed to validate the Age-Related Eye Diseases Study (AREDS) simplified severity scale of AMD classification using 5- and 10-year incident late AMD data from the population-based Blue Mountains Eye Study (BMES) cohort., Design: Comparative study of population-based cohort and clinical trial., Participants: Blue Mountains Eye Study participants 40 to 97 years of age at baseline (n = 2134) and AREDS participants 55 to 80 years of age (n = 3640)., Methods: In the BMES, AMD lesions were graded from stereoscopic color photographs and were classified according to the AREDS simplified severity scale. The AREDS simplified scale calculates a risk score based on the number of early AMD risk factors (large drusen and pigment abnormalities) in both eyes that can range from 0 to 4., Main Outcome Measures: Five- and 10-year incident late AMD (presence of geographic atrophy or choroidal neovascularization)., Results: The AREDS simplified scale performed similarly when applied to both the BMES population-based participants and the AREDS clinical trial-based participants in predicting 5- and 10-year incidence of late AMD. For scores 0 to 4, the 5-year incidence rates for the BMES compared with the AREDS were 0.2% versus 0.4%, 3.1% versus 3.1%, 12.1% versus 11.8%, 13.5% versus 25.9%, and 47.1% versus 47.3%, respectively. The corresponding 10-year incidence rates for the BMES compared with the AREDS were 0.7% versus 1.5%, 7.3% versus 8.4%, 36.6% versus 27.6%, 20.0% versus 52.7%, and 75.0% versus 71.4%, respectively., Conclusions: The AREDS simplified severity scale classified late AMD risk levels similarly when applied to population-based and clinical trial samples. These results support the robustness of the AREDS simplified severity scale., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Myopia is the largest cause of uncorrected visual impairments globally and its recent dramatic increase in the population has made it a major public health problem. In observational studies, educational attainment has been consistently reported to be correlated to myopia. Nonetheless, correlation does not imply causation. Observational studies do not tell us if education causes myopia or if instead there are confounding factors underlying the association. In this work, we use a two-step least squares instrumental-variable (IV) approach to estimate the causal effect of education on refractive error, specifically myopia. We used the results from the educational attainment GWAS from the Social Science Genetic Association Consortium to define a polygenic risk score (PGRS) in three cohorts of late middle age and elderly Caucasian individuals (N = 5,649). In a meta-analysis of the three cohorts, using the PGRS as an IV, we estimated that each z-score increase in education (approximately 2 years of education) results in a reduction of 0.92 ± 0.29 diopters (P = 1.04 × 10(-3) ). Our estimate of the effect of education on myopia was higher (P = 0.01) than the observed estimate (0.25 ± 0.03 diopters reduction per education z-score [∼2 years] increase). This suggests that observational studies may actually underestimate the true effect. Our Mendelian Randomization (MR) analysis provides new evidence for a causal role of educational attainment on refractive error., (© 2015 WILEY PERIODICALS, INC.)

Purpose: To determine the prevalence of age-related cataract and its ancestral and socioeconomic risk factors in a multi-ethnic Asian population., Design: Population-based, cross-sectional study., Participants: A total of 10 033 adults (3353 Chinese, 3280 Malays, and 3400 Indians) aged >40 years in the Singapore Epidemiology of Eye Diseases Study., Methods: Study participants were invited for a structured interview and received a standardized comprehensive eye examination. Digital lens photographs were taken from eyes of each participant and graded for nuclear, cortical, and posterior subcapsular (PSC) cataract, following the Wisconsin Cataract Grading System. Prevalence data were compared with the Blue Mountains Eye Study (BMES) in Australia. Information on medical and lifestyle factors was collected using questionnaires and blood samples. To increase the precision of racial definition, genetic ancestry was derived from genome-wide single nucleotide polymorphism markers using principal component analysis. Regression models were used to investigate the association of cataract with socioeconomic factors (education and income) and genetic ancestry., Main Outcome Measures: Age-related cataract., Results: A total of 8750 participants (94.0%) had gradable lens photographs. The age-standardized prevalence of cataract surgery in Chinese (16.0%), Malays (10.6%), and Indians (20.2%) was higher than in white subjects (4.1%). We found the age-standardized cataract prevalence in Chinese (30.4%), Malays (37.8%), and Indians (33.1%) was higher than in whites (18.5%). Cataract was 1.5 to 2 times more common in Asians and began 10 years earlier than in white subjects. Malays had significantly higher age-standardized prevalence of nuclear, cortical, and PSC cataract than Chinese (P<0.001). The severity of nuclear, cortical, and PSC cataract was significantly correlated with genetic ancestry in our South East Asian population. Less education and lower income were associated with cataract for Chinese and Indians but not Malays. The presence of visual impairment associated with cataract was higher in people aged ≥60 years and Malays., Conclusions: We showed that people of different Asian ethnicities had a higher prevalence and earlier age of onset of cataract than Europeans. People of Malay ancestry have a greater severity for all cataract subtypes than people of Chinese ancestry. Education and income were associated with cataract for certain Asian subgroups., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Importance: The natural course and prognosis of medium drusen and risk factors associated with the incidence and progression of this lesion type in age-related macular degeneration (AMD) are not well understood., Objective: To assess the 15-year incidence and progression of medium drusen and associated risk factors., Design, Setting, and Participants: Population-based cohort in the Blue Mountains region, west of Sydney, Australia. Included in the study were 3654 participants 49 years or older who attended baseline examinations of the Blue Mountains Eye Study (1992-1994), and 75.8%, 76.7%, and 56.1% of survivors who attended the 5-year, 10-year, and 15-year follow-up examinations, respectively., Main Outcomes and Measures: Color retinal fundus photographs were obtained at each examination. The incidence and progression of medium drusen (maximum diameter, 63 to <125 µm) were assessed using Kaplan-Meier product-limit survival methods, controlling for competing risk of death. Factors associated with a 15-year incidence of medium drusen were assessed using discrete logistic regression models after adjusting for age, sex, smoking status, serum lipid levels, systemic and dietary factors, and CFH rs1061170 and ARMS2 rs10490924 polymorphisms. Associations between lesion characteristics and the progression to late AMD were assessed using generalized estimating equation models and eye-specific data., Results: Among 1317 participants at risk, the 15-year cumulative incidence of medium drusen was 13.9% (n = 281). Increasing age (per decade older) (odds ratio [OR], 1.4; 95% CI, 1.2-1.8) and the presence of at least 3 risk alleles of the CFH rs1061170 or ARMS2 rs10490924 genes (OR, 2.1; 95% CI, 1.1-4.1) were associated with a higher incidence. There was no association between past smoking (OR, 0.8; 95% CI, 0.6-1.1) or current smoking (OR, 0.6; 95% CI, 0.4-1.1) and the development of medium drusen. The progression rate to late AMD in eyes with both medium drusen and retinal pigmentary abnormalities was 4-fold higher than that in eyes with medium drusen alone. Larger total area and central location of medium drusen were associated with a greater likelihood of the progression to worse stages of AMD., Conclusions and Relevance: Older age and the presence of CFH and ARMS2 risk alleles are 2 main risk factors associated with the development of medium drusen. The copresence of medium drusen plus retinal pigment epithelium abnormalities signals a greater risk of the progression to late AMD than the presence of medium drusen alone.

Purpose: To investigate the relationship between metabolic syndrome (MetS) and its components with the risk of early- and late-stage age-related macular degeneration (AMD)., Methods: A prospective cohort of individuals aged older than or equal to 49 years were followed up over a period of 10 years in the Blue Mountains Eye Study, Australia. MetS components were measured at baseline (1992-1994), 5-year (1997-1999), and 10-year (2002-2004) follow-ups. Incident cases of early and late AMD were diagnosed using standard photographic grading of retinal images of 2,218 participants at risk. Mixed-effect logistic regression was conducted to explore the relationship between MetS (and its components) with subsequent development of early/late AMD., Results: Over the 10-year follow-up, early AMD developed in 12% and late AMD in 3% of participants at risk. Amongst subjects aged younger than or equal to 70 years, MetS was associated with the incidence of late AMD. Of the five MetS components, obesity, high glucose, and high triglyceride were associated with the increased incidence of late AMD during the 10-year follow-up. There was no evidence of effect of MetS and its components on the risk of early AMD., Conclusion: Metabolic syndrome, obesity, high glucose, and high triglycerides were predictors of progression to late AMD. These data provide additional insights into the pathogenesis of AMD.

Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness worldwide. We performed a genome-wide association study in an Australian discovery cohort comprising 1,155 cases with advanced POAG and 1,992 controls. We investigated the association of the top SNPs from the discovery stage in two Australian replication cohorts (932 cases and 6,862 controls total) and two US replication cohorts (2,616 cases and 2,634 controls total). Meta-analysis of all cohorts identified three loci newly associated with development of POAG. These loci are located upstream of ABCA1 (rs2472493[G], odds ratio (OR) = 1.31, P = 2.1 × 10(-19)), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 × 10(-10)) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 × 10(-10)). Using RT-PCR and immunolabeling, we show that these genes are expressed within human retina, optic nerve and trabecular meshwork and that ABCA1 and AFAP1 are also expressed in retinal ganglion cells.

Objectives: The aims of this study were to investigate the potential unmet need for hearing services among older people attending low-vision rehabilitation, and pilot a "Hearing Screening and Education Model" (HSEM) of intervention to promote use of hearing services and aids among these individuals., Design: In the Vision-Hearing project, 300 clients attending low-vision clinics in Sydney, Australia, participated in baseline interviews and the HSEM (2010-2011). The HSEM consisted of: (1) standard pure-tone audiometry; (2) discussion of hearing loss and implications of dual sensory impairment; and (3) provision of information on hearing services and facilitated referral. Those with hearing loss who did not own hearing aids, reported low use (<1 hr/day), or used a single aid with bilateral loss were referred for full assessment by an audiologist and to the follow-up arm of the study (n = 210). Follow-up interviews were conducted within 12 months to ascertain actions taken and audiological and other health outcomes., Results: Of 169 participants in the follow-up study, 68 (40.2%) sought help for hearing loss within 12 months. Help-seekers had higher mean hearing handicap scores at baseline compared with non-help-seekers. The majority of help-seekers (85.3%) underwent a complete hearing assessment. Fifty-four percent (n = 37) were recommended hearing aids and the majority of these (n = 27) obtained new hearing aids. Seven participants had existing aids adjusted, and 3 obtained alternate assistive listening devices. Almost half of those receiving new aids or adjustments to hearing aids reported low use (<1 hr/day) at follow-up. Among help-seekers, 40% were unsure or did not believe their audiologist knew of their visual diagnosis. Of concern, 60% of participants did not seek help largely due to perceptions their hearing loss was not bad enough; the presence of competing priorities; concerns over dealing with vision loss and managing hearing aids with poor vision., Conclusions: Hearing- and vision-rehabilitation services need to better screen for, and take account of, dual sensory impairment among their older clients. If audiologists are made more aware of visual conditions affecting their clients, they may be better placed to facilitate access to appropriate technologies and rehabilitation, which may improve aid retention and benefit.

Purpose: We compared early age-related macular degeneration (AMD) lesion characteristics between white Australians and Singaporean Asians., Methods: Participants of the Blue Mountains Eye Study (BMES; whites, n = 3508) and the Singapore Epidemiology of Eye Disease Study (SEED; Malay, n = 3280, Indian, n = 3400, and Chinese, n = 3353) underwent examinations, including retinal photography. The AMD lesions were assessed following the Wisconsin AMD grading protocol by the same photographic grader. Prevalence and characteristics of early AMD lesions were compared between the BMES and the SEED. The associations between ethnicity and early AMD lesion types were analyzed using logistic regression models adjusting for age, sex, smoking status, lipids, and genetic polymorphisms associated with AMD., Results: After age-standardization to the BMES population, the prevalence of distinct soft drusen was significantly higher in Singaporeans compared to Australians (23.9%, 95% confidence interval [CI] 22.9-25.0 vs. 6.2%, 95% CI 5.3-7.0), with an adjusted odds ratio (OR) of 4.6 (95% CI 3.4-6.0). In contrast, the prevalence of indistinct soft or reticular drusen was significantly lower in Singaporeans compared to Australians (6.5%, 95% CI 5.9-7.1 vs. 8.3%, 95% CI 7.4-9.3, with nonsignificant adjusted OR of 1.2, 95% CI 0.8-1.7). Soft drusen of any type were present frequently at the inner and outer macula (within a zone ≥500 to <3000 μm radius from the foveal center) among Singaporeans, while among Australians soft drusen were present more frequently at the central macula (<500 μm radius)., Conclusions: Singaporean Asians had a milder spectrum of early AMD lesions and lesion characteristics (predominantly distinct soft drusen and noncentral location) compared to white Australians., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Purpose: To describe methods to harmonize the classification of age-related macular degeneration (AMD) phenotypes across four population-based cohort studies: the Beaver Dam Eye Study (BDES), the Blue Mountains Eye Study (BMES), the Los Angeles Latino Eye Study (LALES), and the Rotterdam Study (RS)., Methods: AMD grading protocols, definitions of categories, and grading forms from each study were compared to determine whether there were systematic differences in AMD severity definitions and lesion categorization among the three grading centers. Each center graded the same set of 60 images using their respective systems to determine presence and severity of AMD lesions. A common 5-step AMD severity scale and definitions of lesion measurement cutpoints and early and late AMD were developed from this exercise., Results: Applying this severity scale changed the age-sex adjusted prevalence of early AMD from 18.7% to 20.3% in BDES, from 4.7% to 14.4% in BMES, from 14.1% to 15.8% in LALES, and from 7.5% to 17.1% in RS. Age-sex adjusted prevalences of late AMD remained unchanged. Comparison of each center's grades of the 60 images converted to the consortium scale showed that exact agreement of AMD severity among centers varied from 61.0-81.4%, and one-step agreement varied from 84.7-98.3%., Conclusion: Harmonization of AMD classification reduced categorical differences in phenotypic definitions across the studies, resulted in a new 5-step AMD severity scale, and enhanced similarity of AMD prevalence among the four cohorts. Despite harmonization it may still be difficult to remove systematic differences in grading, if present.

Purpose: To compare mortality risk between cataract surgical patients with corrected and persistent visual impairment., Design: Cohort study., Methods: A total of 1864 consecutive patients, aged ≥64 years, undergoing phacoemulsification surgery at Westmead Hospital were followed annually for 5 years postoperatively. Visual impairment status in the surgical eye was categorized as none (presenting visual acuity [VA], ≥20/40), mild (VA <20/40-20/60), or moderate-severe (VA <20/60). All-cause mortality was obtained from the Australian National Death Index., Results: Of 901 patients with moderate-severe visual impairment before surgery, 60.4% (n = 544), 15.5% (n = 140), and 24.1% (n = 217) had no, mild, or moderate-severe visual impairment in the surgical eye, respectively, 1 month postoperatively. Age-standardized 5-year mortality rates were nonsignificantly lower in patients with either mild (24.7%, 95% confidence interval [CI] 16.5%-32.9%) or no visual impairment (24.1%, 95% CI 19.9%-28.4%) post surgery compared to that in patients whose moderate-severe visual impairment persisted (30.6%, 95% CI 23.3%-37.9%). After adjusting for age, sex, smoking, body mass index, and individual comorbid conditions, such as hypertension, diabetes, angina, myocardial infarction, stroke, transient ischemic attack, and kidney disease, patients with no visual impairment 1 month postoperatively had a lower mortality risk (HR 0.73, 95% CI 0.52-1.01) compared to those with persistent moderate-severe visual impairment after surgery. This finding was significant (HR 0.71, 95% CI 0.51-0.99) after additional adjustment for number of medications taken (continuous variable) and number (≥3 vs <3) of comorbid conditions., Conclusion: Correcting moderate-severe visual impairment in older patients with phacoemulsification surgery was associated with a lower mortality risk, compared to surgical patients whose visual impairment persisted postoperatively., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Prediction models for age-related macular degeneration (AMD) based on case-control studies have a tendency to overestimate risks. The aim of this study is to develop a prediction model for late AMD based on data from population-based studies., Design: Three population-based studies: the Rotterdam Study (RS), the Beaver Dam Eye Study (BDES), and the Blue Mountains Eye Study (BMES) from the Three Continent AMD Consortium (3CC)., Participants: People (n = 10,106) with gradable fundus photographs, genotype data, and follow-up data without late AMD at baseline., Methods: Features of AMD were graded on fundus photographs using the 3CC AMD severity scale. Associations with known genetic and environmental AMD risk factors were tested using Cox proportional hazard analysis. In the RS, the prediction of AMD was estimated for multivariate models by area under receiver operating characteristic curves (AUCs). The best model was validated in the BDES and BMES, and associations of variables were re-estimated in the pooled data set. Beta coefficients were used to construct a risk score, and risk of incident late AMD was calculated using Cox proportional hazard analysis. Cumulative incident risks were estimated using Kaplan-Meier product-limit analysis., Main Outcome Measures: Incident late AMD determined per visit during a median follow-up period of 11.1 years with a total of 4 to 5 visits., Results: Overall, 363 participants developed incident late AMD, 3378 participants developed early AMD, and 6365 participants remained free of any AMD. The highest AUC was achieved with a model including age, sex, 26 single nucleotide polymorphisms in AMD risk genes, smoking, body mass index, and baseline AMD phenotype. The AUC of this model was 0.88 in the RS, 0.85 in the BDES and BMES at validation, and 0.87 in the pooled analysis. Individuals with low-risk scores had a hazard ratio (HR) of 0.02 (95% confidence interval [CI], 0.01-0.04) to develop late AMD, and individuals with high-risk scores had an HR of 22.0 (95% CI, 15.2-31.8). Cumulative risk of incident late AMD ranged from virtually 0 to more than 65% for those with the highest risk scores., Conclusions: Our prediction model is robust and distinguishes well between those who will develop late AMD and those who will not. Estimated risks were lower in these population-based studies than in previous case-control studies., (Copyright © 2013. Published by Elsevier Inc.)

Purpose: To examine early age-related macular degeneration (AMD) lesion characteristics and risk factors associated with the long-term development and progression of geographic atrophy (GA)., Design: Population-based cohort., Participants: Of 3654 participants aged ≥49 years in the Blue Mountains Eye Study, 75.8%, 76.7%, and 56.1% of survivors attended the 5-, 10-, and 15-year follow-up examinations, respectively., Methods: Retinal photographs were taken at each visit. Incident GA was confirmed using a side-by-side grading method. Computer planimetry was used to measure the area involved by GA. Fast and slow/normal progression rates were defined as GA area enlargement by ≥2 and <2 mm(2)/year, respectively. Incident GA was estimated using the Kaplan-Meier product-limit method. Early AMD lesion characteristics were assessed for association with GA incidence using eye-specific data and generalized estimating equation models adjusting for age, current smoking, and presence of risk alleles of the complement factor H (CFH) or age-related maculopathy susceptibility 2 (ARMS2) genes, genotyped or imputed using genome-wide scan data., Main Outcome Measures: Incidence and progression of GA., Results: By excluding 41 subjects with GA at baseline, of 2503 participants at risk of GA, incident pure GA (without coexisting neovascular AMD lesions) was confirmed in 57 participants, with a 15-year incidence of 3.6%. Baseline early AMD lesion characteristics associated with GA incidence included drusen type (soft indistinct: odds ratio [OR], 59.0; 95% confidence interval [CI], 20.4-171.0; reticular drusen: OR, 13.9; 95% CI, 4.0-47.6); drusen location within a 500-μm radius of the fovea (OR, 15.1; 95% CI, 7.4-30.8); drusen area greater than 375 μm in diameter (OR, 10.1; 95% CI, 4.0-25.6); presence of retinal pigment epithelial depigmentation (OR, 9.0; 95% CI, 4.1-19.8); or hyperpigmentation (OR, 12.0; 95% CI, 6.1-23.5), referenced to subjects with no or hard drusen only. Fast progression was more frequent among current smokers at baseline, subjects with the CFH or ARMS2 risk genotypes, and pseudophakic eyes., Conclusions: Early AMD lesion characteristics (type, location, area involved) were strongly associated with higher long-term risk of developing GA independent of age, smoking, and AMD genetic susceptibility from the CFH or ARMS2 genes. Known AMD risk factors also were more frequently present among quickly progressing GA cases., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the change in visual acuity (VA) and incidence of visual impairment (VI) in an older population over a 15-year period., Design: Population-based cohort., Participants: Of the 3654 participants of the Blue Mountains Eye Study (BMES) baseline examination from 1992 through 1994, 1149 were re-examined during the 15-year follow-up between 2007 and 2010., Methods: Best-corrected VA by means of subjective refraction was measured with a logarithm of the minimum angle of resolution chart using Early Treatment Diabetic Retinopathy Study methods at each examination., Main Outcome Measures: Unilateral VI was defined as VA worse than 20/40 and blindness was defined as VA worse than 20/200 in the worse eye. Incident bilateral VI and blindness were determined according to VA in the better eye at the 15-year visit. Doubling of the visual angle was defined as a loss of 15 letters or more from baseline to the 15-year visit. Halving of the visual angle was defined as a VA improvement of 15 letters or more over the same period. Causes of VI were determined at examination, by photographic grading, and from medical records., Results: Cumulative 15-year incidence of unilateral and bilateral VI was 12.3% (95% confidence interval [CI], 11.0-13.6) and 5.2% (95% CI, 4.3-6.1), respectively, and for unilateral and bilateral blindness, the cumulative incidence was 3.7% (95% CI, 3.0-4.4) and 0.9% (95% CI, 0.5-1.3), respectively. These incidence rates increased significantly with increasing age (P<0.01 for trend). Doubling and halving of the visual angle occurred in 6.9% (95% CI, 5.9-7.9) and 1.6% (95% CI, 1.0-2.2) of participants, respectively. Cataract accounted for 48.5% of unilateral and bilateral incident VI, followed by age-related macular degeneration (26.9%). Age-related macular degeneration accounted for 56.9% of unilateral and bilateral incident blindness cases, followed by cataract (20.7%)., Conclusions: These data provide population-based estimates of long-term incidence of visual impairment among older persons. Our estimate for cumulative incidence of blindness, accounting for competing risk of death, was similar to that of the Beaver Dam Eye Study (BDES) after age standardization. However, our estimate for cumulative incidence of VI was lower compared with that observed in the BDES population. This difference may be explained in part by a higher mortality rate among our population., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Congenital cataract is the most common cause of treatable visual impairment in children worldwide. Mutations in many different genes lead to congenital cataract. Recently, mutations in the receptor tyrosine kinase gene, EPHA2, have been found to cause congenital cataract in six different families. Although these findings have established EPHA2 as a causative gene, the total contribution of mutations in this gene to congenital cataract is unknown. In this study, for the first time, a population-based approach was used to investigate the frequency of disease causing mutations in the EPHA2 gene in inherited cataract cases in South-Eastern Australia. A cohort of 84 familial congenital or juvenile cataract index cases was screened for mutations in the EPHA2 gene by direct sequencing. Novel changes were assessed for segregation with the disease within the family and in unrelated controls. Microsatellite marker analysis was performed to establish any relationship between families carrying the same mutation. We report a novel congenital cataract causing mutation c.1751C>T in the EPHA2 gene and the previously reported splice mutation c.2826-9G>A in two new families. Additionally, we report a rare variant rs139787163 potentially associated with increased susceptibility to cataract. Thus mutations in EPHA2 account for 4.7% of inherited cataract cases in South-Eastern Australia. Interestingly, the identified rare variant provides a link between congenital and age-related cataract.

It is unknown whether diet quality is associated with microvascular structure. The present study aimed to investigate the relationship between diet quality, reflecting adherence to dietary guidelines, with retinal microvascular calibre in older adults. The dietary data of 2720 Blue Mountains Eye Study participants, aged 50+ years, were collected using a semi-quantitative FFQ. A modified version of the Healthy Eating Index for Australians was developed to determine total diet scores (TDS). Fundus photographs were taken and retinal vascular calibre measured using computer-assisted techniques and summarised. After adjusting for age, sex, BMI, mean arterial blood pressure, smoking, serum glucose, leucocyte count and history of diagnosed stroke or CHD, persons with higher TDS had healthier retinal vessels cross-sectionally, with wider retinal arteriolar calibre (by approximately 3 μm, comparing the highest with the lowest quartile of TDS, Ptrend = 0·0001) and narrower retinal venular calibre (by approximately 2·5 μm; Ptrend = 0·02). In younger subjects aged ≤65 years, increasing TDS (lowest to the highest quartile) was associated with healthier retinal vessels: approximately 4·4 μm wider retinal arteriolar (Ptrend < 0·0001) and approximately 2·3 μm narrower venular calibre (Ptrend = 0·03). After multivariable adjustment, however, baseline TDS were not associated with retinal arteriolar (Ptrend = 0·89) or venular calibre (Ptrend = 0·25), 5 years later. Also, baseline TDS were not associated with the 5-year change in retinal arteriolar (β = 0·14; P=0·29) or venular calibre (β = - 0·26; P=0·07). Greater compliance with published dietary guidelines (higher diet quality) was cross-sectionally associated with wider retinal arterioles and narrower venules, indicating better retinal microvascular health.

Purpose: Keratoconus is a common complex corneal ectasia that can lead to severe visual impairment. Although a genetic component is well recognized, the genetic risk factors for keratoconus are yet to be fully elucidated. A recent genome-wide association study (GWAS) by Li et al. identified 15 potentially associated single nucleotide polymorphisms (SNPs). Here, we aimed to replicate these associations, and conduct a meta-analysis of the current and previous studies., Methods: We genotyped the 15 reported associated SNPs in 524 Australian Caucasian cases with keratoconus and 2761 controls. Association analysis was conducted in PLINK. A meta-analysis of this study with the adjusted P values of the previously published GWAS was conducted using the method of Fisher to combine P values., Results: Our Australian cohort showed association (P < 0.003) at SNPs near RAB3GAP1, KCND3, IMMPL2, and in a gene desert on chromosome 13q33.3, providing evidence of replication of the published results. The meta-analysis showed SNP rs4954218 near RAB3GAP1 gene was associated significantly with keratoconus, with P = 9.26 × 10(-9) passing the genome-wide significance level., Conclusions: Although the mechanism of disease association is yet to be determined, SNP rs4954218 is associated consistently with keratoconus and likely tags a functional variant that contributes to disease susceptibility.

Objective: To determine whether regular aspirin use is associated with a higher risk for developing age-related macular degeneration (AMD) by using analyzed data from a 15-year prospective cohort., Methods: A prospective analysis was conducted of data from an Australian population-based cohort with 4 examinations during a 15-year period (1992-1994 to 2007-2009). Participants completed a detailed questionnaire at baseline assessing aspirin use, cardiovascular disease status, and AMD risk factors. Age-related macular degeneration was graded side-by-side from retinal photographs taken at each study visit to assess the incidence of neovascular (wet) AMD and geographic atrophy (dry AMD) according to the international AMD classification., Results: Of 2389 baseline participants with follow-up data available, 257 individuals (10.8%) were regular aspirin users and 63 of the 2389 developed neovascular AMD. Persons who were regular aspirin users were more likely to have incident neovascular AMD: the 15-year cumulative incidence was 9.3% in users and 3.7% in nonusers. After adjustment for age, sex, smoking, history of cardiovascular disease, systolic blood pressure, and body mass index, persons who were regular aspirin users had a higher risk of developing neovascular AMD (odds ratio [OR], 2.46; 95% CI, 1.25-4.83). The association showed a dose-response effect (multivariate-adjusted P = .01 for trend). Aspirin use was not associated with the incidence of geographic atrophy (multivariate-adjusted OR, 0.99; 95% CI, 0.59-1.65)., Conclusion: Regular aspirin use is associated with increased risk of incident neovascular AMD, independent of a history of cardiovascular disease and smoking.

Purpose: To ascertain if single nucleotide polymorphisms (SNPs) involved in the determination of central corneal thickness, optic disc area, and vertical cup-to-disc ratio (VCDR) also are associated with open-angle glaucoma (OAG)., Design: Retrospective case-control genetic association study., Methods: A total of 16 SNPs associated with central corneal thickness, optic disc area, and VCDR were genotyped in 876 OAG cases and 883 normal controls. To determine if the SNPs were also correlated with OAG severity, the cohort was stratified into advanced OAG (n = 326) and nonadvanced OAG (n = 550). Both the cases and controls were of European descent and were recruited from within Australia., Results: Two VCDR SNPs were found to be significantly associated with OAG after correction for multiple testing. The 2 SNPs were rs10483727, found adjacent to the SIX1 gene (P = 6.2 × 10(-06); odds ratio, 1.38; 95% confidence interval, 1.20 to 1.59), and rs1063192, found within the CDKN2B gene (P = 2.2 × 10(-05); odds ratio, 0.74; 95% confidence interval, 0.64 to 0.85). The CDKN2B variant rs1063192 also was found to be associated more strongly with advanced OAG., Conclusions: The findings from this study indicate that variants influencing VCDR are also risk alleles for OAG in our Australian cohort of European descent. The identification of SIX1 and CDKN2B as susceptibility loci will assist in understanding the pathologic mechanisms involved in the development of OAG., (Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the prevalence of epiretinal membrane (ERM) and its risk factors in an Indian population and compare the findings with other populations., Methods: The Singapore Indian Eye Study is a population-based survey of 3400 Asian Indians aged between 40 and 80 years. A comprehensive ophthalmic examination, standardized interviews, and laboratory blood tests were performed. Digital retinal fundus photographs were assessed for the presence of ERM following the definitions used in the Blue Mountains Eye Study (BMES). ERM was classified into a less severe form termed "cellophane macular reflex" (CMR) and a more severe form termed "preretinal macular fibrosis" (PMF) and also as primary and secondary (if it was associated with retinal pathology or cataract surgery)., Results: A total of 3328 persons (mean age 57.8 ± [SD] 10.1 years, and 50.2% male) provided data in this study. The age-standardized prevalence of ERM was 7.6% (95% confidence interval [CI], 6.8-8.6), CMR 4.1% (95% CI, 3.5-4.9), and PMF 3.5% (95% CI, 2.9-4.2). Older age (odds ratio [OR], 1.09; 95% CI, 1.07-1.11, per year increase), increasing myopic refraction (OR, 1.14; 95% CI, 1.07-1.22, per diopter decrease), and narrower retinal arteriolar diameter (OR, 1.02; 95% CI, 1.00-1.03, per μm decrease) were significantly associated with primary ERM., Conclusions: The age-standardized prevalence of ERM in the Indian population in Singapore was 7.6%. This is similar to Malays in Singapore (8.0%) and higher than the prevalence in whites in Australia (4.7%). Significant factors associated with primary ERM were older age, myopia, and narrower retinal arteriolar diameter.

Background: This paper describes the rationale and design of the ENVIS-ion Study, which aims to determine whether low-dose aspirin reduces the development of white matter hyper-intense (WMH) lesions and silent brain infarction (SBI). Additional aims include determining whether a) changes in retinal vascular imaging (RVI) parameters parallel changes in brain magnetic resonance imaging (MRI); b) changes in RVI parameters are observed with aspirin therapy; c) baseline cognitive function correlates with MRI and RVI parameters; d) changes in cognitive function correlate with changes in brain MRI and RVI and e) whether factors such as age, gender or blood pressure influence the above associations., Methods/design: Double-blind, placebo-controlled trial of three years duration set in two Australian academic medical centre outpatient clinics. This study will enrol 600 adults aged 70 years and over with normal cognitive function and without overt cardiovascular disease. Subjects will undergo cognitive testing, brain MRI and RVI at baseline and after 3 years of study treatment. All subjects will be recruited from a 19,000-patient clinical outcome trial conducted in Australia and the United States that will evaluate the effects of aspirin in maintaining disability-free longevity over 5 years. The intervention will be aspirin 100 mg daily versus matching placebo, randomized on a 1:1 basis., Discussion: This study will improve understanding of the mechanisms at the level of brain and vascular structure that underlie the effects of aspirin on cognitive function. Given the limited access and high cost of MRI, RVI may prove useful as a tool for the identification of individuals at high risk for the development of cerebrovascular disease and cognitive decline., Trial Registration: clinicaltrials.gov Identifier: NCT01038583.