Ava Grace Tan

Use of Inhaled and Oral Corticosteroids and the Long-term Risk of Cataract

OBJECTIVE Longitudinal associations between inhaled and oral corticosteroid use and 10-year incident cataract were examined. DESIGN Population-based cohort study. PARTICIPANTS The Blue Mountains Eye Study examined 3654 Australians aged 49 years or older (1992-1994); 2335 were re-examined after 5 years and 1952 were re-examined after 10 years (75.1%, 75.6% of survivors, respectively). METHODS Questionnaires were used to assess inhaled and oral corticosteroid use at baseline. Past users were participants who had used these medications for at least 1 month in the past but were not using them at baseline. Current users were those who were using these medications at baseline and had been doing so for at least 1 month. Ever users combined past and current users. MAIN OUTCOME MEASURES Lens photographs were obtained at each examination and graded for nuclear, cortical, and posterior subcapsular (PSC) cataracts following the Wisconsin Cataract Grading System. Participants without a specific subtype of cataract in either eye at baseline were considered to be at risk of that type of cataract developing over the 10-year follow-up. Incidence of each cataract subtype in this report refers to person-specific, first-eye incidence. RESULTS At baseline, 103 participants were current and 120 past users of inhaled corticosteroids, and 31 were current and 147 were past users of oral corticosteroids. Current users had a greater risk of developing PSC cataract after adjustment for age and gender (inhaled: odds ratio [OR] 2.50, 95% confidence interval [CI] 1.33-4.69; oral: OR 4.11; 95% CI 1.67-10.08) and nuclear cataract (inhaled: OR 2.04, 95% CI 1.21-3.43; oral: OR 3.45, 95% CI 1.26-9.43) but not cortical cataract. Interaction between inhaled and oral corticosteroid use was significant for PSC (P = 0.01) and nuclear (P = 0.02) cataract incidence. In subgroup analyses, only individuals who used both inhaled and oral steroids were at increased risk of PSC cataract (after adjusting for age, sex, smoking, hypertension, diabetes, and education levels; OR 4.76, 95% CI 2.59-8.74), comparing ever users of both with users of neither. CONCLUSIONS High long-term risks of PSC and nuclear cataract development were found for users of combined inhaled and oral corticosteroids.

Computer‐assisted retinal vessel measurement in an older population: correlation between right and left eyes

This study assessed the correlation between computer‐assisted retinal vessel measurements of right and left eyes, from subjects in a defined, community‐based older population. Retinal photographs from participants in the Blue Mountains Eye Study were digitized. All retinal arterioles and venules located 0.5−1.0 disc diameters from the optic disc margin were identified and a computer program measured their diameters. Pearson correlation (R2) statistic was used to assess the correlation in a random subsample of 1546 images. Substantial correlation between right and left eye measurements was found for summary indices of retinal arterioles (R2 = 0.70) and venules (R2 = 0.77). Higher correlation was found for intragrader (R2 0.75−079) than for intergrader assessment (R2 0.67−0.72). Moderate correlation was found in arteriole‐to‐venule ratio assessed by the same (R2 = 0.57) or different (R2 = 0.52) graders. Measurements from one eye can thus adequately represent the retinal vessel diameters of a person.

Fractal dimension of the retinal vasculature and risk of stroke: a nested case-control study.

Recent studies show associations between retinal vascular changes and small infarcts detected on brain imaging, or clinical stroke.1 Fractal dimension has been used as a global measure of the geometric pattern of the retinal vasculature2,3 potentially representing the complex branching pattern of the microvasculature, including the cerebral microvasculature. We have developed an automatic method to assess spectrum fractal dimension (SFD) of the retinal microvasculature using Fourier-transformed images.4,5 Two previous studies have reported cross-sectional associations between retinal fractal dimension and lacunar stroke.6,7 In this study, we aimed to examine the association between baseline SFD and stroke incidence using a case-control sample nested in the Blue Mountains Eye Study (BMES). ### Methods. The BMES is a population-based cohort study of an urban population aged 49 years or older (n = 3,654), representing 82.4% of eligible population in a defined area of the Blue Mountains region, Australia.1 Stroke cases were defined among participants with no past history of stroke at baseline (1992–1994) but who developed stroke during the subsequent 5 years (1997–1999), or who died from stroke or stroke-related causes by late 2005. Detailed definitions of stroke events and mortality are shown in …

Smoking, Socioeconomic Factors, and Age-Related Cataract: The Singapore Malay Eye Study

OBJECTIVE To describe the relationship of smoking, sex, and socioeconomic factors with age-related cataract in Malay adults in Singapore. METHODS In a population-based study, 3280 Malay individuals aged 40 to 80 years participated (78.7% response rate). All had interviews, systemic examination, and laboratory investigations. Lens opacity was graded from slitlamp and retroillumination photographs using the Wisconsin Cataract Grading System. Smoking-cataract associations were compared with the Blue Mountains Eye Study in Australia. RESULTS Of 2927 participants (89.2%) with gradable lens photographs, 1338 (45.7%) had cataract. After adjusting for age, sex, body mass index, hypertension, and diabetes, current smokers had a higher prevalence of nuclear cataract (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.46-2.98), cortical cataract (OR, 1.33; 95% CI, 1.02-1.74), posterior subcapsular cataract (OR, 1.39; 95% CI, 1.02-1.91), or any cataract (OR, 1.48; 95% CI, 1.10-1.99). These associations were not seen in the Blue Mountains Eye Study. Primary or lower education (OR, 1.67; 95% CI, 1.06-2.64) and low monthly income (OR, 1.43; 95% CI, 1.09-1.87) were both associated with nuclear cataract, while small-sized public housing was associated with posterior subcapsular cataract (OR, 1.70; 95% CI, 1.28-2.25). Among men, 43.5% currently smoked compared with only 3.2% of women. The population attributable risk of nuclear cataract due to smoking was estimated to be 17.6% in men. CONCLUSIONS Smoking and indicators of low socioeconomic status were associated with cataract in Malay persons, with 1 in 6 nuclear cataract cases in men attributable to smoking. Smoking-cataract associations were stronger in Malay than in white persons.

The Long-term Relation among Retinal Arteriolar Narrowing, Blood Pressure, and Incident Severe Hypertension

The authors assessed associations between retinal vascular signs and incident severe hypertension in an older population-based cohort. At baseline (1992-1994), 3,654 residents aged 49-97 years living in the Blue Mountains area west of Sydney, Australia, were examined; respectively, 2,335 (75.1%) and 1,952 (76%) survivors were reexamined 5 and 10 years later. Retinal arteriolar and venular calibers were measured, and average central retinal artery and central retinal vein equivalents for that eye were estimated. Severe hypertension was defined by previous diagnosis of hypertension plus antihypertensive medication use or by systolic blood pressure > or =160 mmHg and/or diastolic blood pressure > or =100 mmHg at examinations. Of the 1,424 participants at risk, 618 developed severe hypertension over 10 years (cumulative incidence = 47.7%, 95% confidence interval: 44.9, 50.5). Participants who subsequently developed severe hypertension had significantly narrower mean central retinal artery equivalents than those who did not (187.0 vs. 191.9 mum, p < 0.0001). After adjusting for age, sex, body mass index, smoking, mean arterial blood pressure, and plasma glucose and triglyceride levels, baseline narrowing central retinal artery equivalent was associated with increased risk of severe hypertension (per standard deviation reduction, odds ratio = 1.1, 95% confidence interval: 1.1, 1.2; narrowest vs. widest quintile, odds ratio = 1.6, 95% confidence interval: 1.2, 2.1). These findings support structural narrowing in small arteries and arterioles antecedent to clinical onset of severe hypertension.

A Review and Meta-analysis of the Association Between C-Reactive Protein and Age-related Macular Degeneration

Age-related macular degeneration (AMD) is the leading cause of blindness in people over 60 in western countries. Inflammatory markers have been implicated in the development and progression of AMD. C-reactive protein (CRP) is an inflammatory marker known to be associated with cardiovascular disease, and a link between AMD and CRP has been suggested. In this systematic review we summarize the currently available evidence from clinic-based and population-based studies investigating this association. A meta-analysis of evidence from eleven studies (41,690 study participants) shows that high serum levels (>3 mg/L) of CRP are associated with a two-fold likelihood of late onset AMD, compared to low levels (<1mg/L). Sub-group meta-analyses show a higher association in studies using ophthalmoscopic examination, compared to those using photographic grading (pooled odds ratio 3.83 vs 1.36), to determine AMD status, or in clinic-based samples compared to population-based studies.

Prediction of age-related macular degeneration in the general population: the Three Continent AMD Consortium.

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.

Genetic Susceptibility, Dietary Antioxidants, and Long-Term Incidence of Age-Related Macular Degeneration in Two Populations

OBJECTIVE To examine effect modification between genetic susceptibility to age-related macular degeneration (AMD) and dietary antioxidant or fish consumption on AMD risk. DESIGN Pooled data analysis of population-based cohorts. PARTICIPANTS Participants from the Blue Mountains Eye Study (BMES) and Rotterdam Study (RS). METHODS Dietary intakes of antioxidants (lutein/zeaxanthin [LZ], β-carotene, and vitamin C), long-chain omega-3 polyunsaturated fatty acids, and zinc were estimated from food frequency questionnaires. The AMD genetic risk was classified according to the number of risk alleles of CFH (rs1061170) or ARMS2 (rs10490924) as low (no or 1 risk allele) or high (≥ 2 risk alleles). Interactions between dietary intake and genetic risk levels were assessed. Associations between dietary intake and AMD risk were assessed comparing the highest with the 2 lower intake tertiles by genetic risk subgroups using discrete logistic regression, conducted in each study separately and then using pooled data. Participants without AMD lesions at any visit were controls. We adjusted for age and sex in analyses of each cohort sample and for smoking status and study site in pooled-data analyses. MAIN OUTCOME MEASURES All 15-year incident late AMD cases were confirmed by chief investigators of the Beaver Dam Eye Study, BMES, and RS. Intergrader reproducibility was assessed in an early AMD subsample, with 86.4% agreement between BMES and RS graders, allowing for a 1-step difference on a 5-step AMD severity scale. RESULTS In pooled data analyses, we found significant interaction between AMD genetic risk status and LZ intake (P=0.0009) but nonsignificant interactions between genetic risk status and weekly fish consumption (P=0.05) for risk of any AMD. Among participants with high genetic risk, the highest intake tertile of LZ was associated with a >20% reduced risk of early AMD, and weekly consumption of fish was associated with a 40% reduced risk of late AMD. No similar association was evident among participants with low genetic risk. No interaction was detected between β-carotene or vitamin C and genetic risk status. CONCLUSIONS Protection against AMD from greater LZ and fish consumption in persons with high genetic risk based on 2 major AMD genes raises the possibility of personalized preventive interventions.

Metabolic Syndrome Components and Age-Related Cataract: The Singapore Malay Eye Study

PURPOSE To examine the relationship between metabolic syndrome and its components, diabetes mellitus, high blood pressure (BP), obesity, and dyslipidemia, with age-related cataract. METHODS A population-based sample of 2794 Malay adults aged 40 to 80 years in Singapore was used for this analysis. Cataract (n = 1268) was defined as the presence of nuclear, cortical, or posterior subcapsular (PSC) cataract, from standardized grading of lens photographs or previous cataract surgery. Metabolic syndrome was defined as the presence of ≥ 3 of the following components: body mass index (BMI) ≥ 25 kg/m(2), triglycerides ≥ 1.7 mM, high density-lipoprotein (HDL) cholesterol <1.0 mM in men and <1.3 mM in women, BP ≥ 130/85 mm Hg, or use of BP medication and diabetes mellitus. RESULTS Cataract prevalence increased with higher quartiles of blood glucose, systolic BP, and metabolic syndrome components (P trend < 0.0001). The multivariable odds ratio (OR) (95% confidence interval [CI]) of cataract was 1.89 (1.42-2.40) for diabetes, 1.92 (1.47-2.52) for high BP, and 1.27 (1.04-1.55) for metabolic syndrome. Of the individual metabolic syndrome components, high BP was associated with all three cataract types; diabetes was associated with cortical and PSC; low HDL, high BMI, and metabolic syndrome were associated with cortical cataract. The presence of both high BP and diabetes was associated with fourfold odds of having cataract (OR [95% CI] = 4.73 [2.16-10.34]). CONCLUSIONS Metabolic syndrome and its two key components, high BP and diabetes were associated with age-related cataract.

A Computer-Aided Diagnosis System of Nuclear Cataract

Cataracts are the leading cause of blindness worldwide, and nuclear cataract is the most common form of cataract. An algorithm for automatic diagnosis of nuclear cataract is investigated in this paper. Nuclear cataract is graded according to the severity of opacity using slit lamp lens images. Anatomical structure in the lens image is detected using a modified active shape model. On the basis of the anatomical landmark, local features are extracted according to clinical grading protocol. Support vector machine regression is employed for grade prediction. This is the first time that the nucleus region can be detected automatically in slit lamp images. The system is validated using clinical images and clinical ground truth on >5000 images. The success rate of structure detection is 95% and the average grading difference is 0.36 on a 5.0 scale. The automatic diagnosis system can improve the grading objectivity and potentially be used in clinics and population studies to save the workload of ophthalmologists.