Wholegrain and legume consumption and the 5-year incidence of age-related cataract in the Blue Mountains Eye Study.

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.

Incidence, progression and risk factors of age-related cataract in Malays: The Singapore Malay Eye Study.

IMPORTANCE: Long-term data on age-related cataract, a leading cause of blindness and visual impairment, is scarce in Asian populations. BACKGROUND: We report the 6-year incidence and progression of age-related cataract and associated risk factors in Malay adults living in Singapore. DESIGN: Population-based cohort study. PARTICIPANTS: A total of 3280 Malays aged 40+ years participated in baseline examinations of the Singapore Malay Eye Study (2004-2006). Six years later, 1901 (72.1% of eligible) baseline participants were re-examined. METHODS: Cataract was assessed using lens photos, taken during eye examinations, following the Wisconsin Cataract Grading System. MAIN OUTCOMES AND MEASURES: Incidence and progression of cortical, nuclear and posterior subcapsular (PSC) cataract. Poisson regression models and generalized estimating equations models (with Poisson link) were used to assess factors associated with cataract incidence and progression, respectively, adjusting for age, sex and other risk factors. RESULTS: Age-adjusted 6-year incidence of cortical, nuclear and PSC cataract was 14.1%, 13.6% and 8.7%, respectively, and was strongly age-related (P for trend <.001 for all types). Diabetes (relative risk [RR], 1.97; 95% confidence intervals [CI], 1.46-2.67) was associated with incident cortical cataract, hypertension was associated with PSC cataract incidence (RR, 2.09; 95% CI, 1.22-3.61), after multivariable adjustment. Progression occurred in 20.4%, 5.9% and 40.6% of baseline cortical, nuclear and PSC cataract cases, respectively. CONCLUSIONS AND RELEVANCE: Similar to other elderly populations, incidence and progression of cataract were common in this Malay population. Diabetes and hypertension were important modifiable risk factors for cataract, highlighting the importance of systemic health on eye disease.

The Combination of Healthy Diet and Healthy Body Weight Is Associated with Lower Risk of Nuclear Cataract in the Blue Mountains Eye Study.

BACKGROUND: Greater adherence to dietary guidelines has previously been found to be associated with decreased risk of visual impairment. However, whether or not this association extends to age-related cataract, 1 of the leading causes of visual impairment, is unknown. OBJECTIVES: The aim of this study was to assess the association between adherence to dietary guidelines, using total diet score, and incidence of age-related cataract. METHODS: Of 3654 baseline participants of the population-based Blue Mountains Eye Study cohort (1992-1994), 2334 (75.8% survivors) and 1952 (76.7% survivors) were examined after 5 and 10 y, respectively. Cataract was assessed from lens photographs using the Wisconsin Cataract Grading System. Baseline total diet score was calculated from FFQ data following a modified version of the Healthy Eating Index for Australians. OR with 95% CI were estimated using discrete logistic regression analyses, adjusting for age, sex, and other confounders. To test interaction, a cross-product term of 2 factors was included in regression models. RESULTS: Of 2173 participants (84.7% of those returned for 1 or both follow-ups) with total diet score estimated, 57% were women, mean baseline age was 63.9 ± 8.4y, and mean baseline BMI was 26.3 ± 4.3 kg/m2. After multivariable adjustment, baseline total diet score was not associated with incidence of any cataract. A multiplicative interaction was observed between total diet score and BMI for incident nuclear cataract (P-interaction = 0.04): increasing baseline total diet score was associated with decreased risk of nuclear cataract among participants with BMI <25 (per unit increased total diet score, OR: 0.90; 95% CI: 0.81, 0.99; P = 0.02), but not among participants with BMI ≥25 (OR: 1.00; 95% CI: 0.92, 1.10; P = 0.95). CONCLUSIONS: Adherence to dietary guidelines had no appreciable influence on cataract development overall in this older Australian population. However, adherence to dietary guidelines combined with healthy BMI is associated with decreased risk of nuclear cataract, an aging marker.

Six-Year Incidence of and Risk Factors for Cataract Surgery in a Multi-ethnic Asian Population: The Singapore Epidemiology of Eye Diseases Study.

PURPOSE: To report the 6-year incidence of cataract surgery in an Asian population-based cohort of Malay, Indian, and Chinese persons living in Singapore and factors associated with undergoing cataract surgery over the follow-up period. DESIGN: Population-based prospective cohort study. PARTICIPANTS: From 2004 through 2011, 10 033 participants (3280 Malays, 3400 Indians, and 3353 Chinese) 40 years of age or older participated in the Singapore Epidemiology of Eye Diseases Study. Six years later, 6762 participants (78.7% of those eligible, including 1901 Malays [72.1% of eligible], 2200 Indians [75.5% of eligible], and 2661 Chinese [87.7% of eligible]) were re-examined. METHODS: Detailed eye examinations including slit-lamp biomicroscopy were conducted at both visits. Logistic regression models were used to assess factors associated with cataract surgery after adjusting for age, gender, socioeconomic status, and other risk factors. MAIN OUTCOME MEASURE: Incident cataract surgery. RESULTS: The age-adjusted 6-year incidence of cataract surgery was 11.0% (9.5%, 12.6%, and 11.1% for Malays, Indians, and Chinese, respectively) and was strongly age related (P < 0.001 for trend). After adjustment, baseline factors associated with incident cataract surgery included older age (odds ratio [OR], 1.13 per 1-year increase; 95% confidence interval [CI], 1.11-1.14), diabetes (OR, 1.90; 95% CI, 1.54-2.33), myopia (OR, 1.78; 95% CI, 1.44-2.20), and baseline presence of any cataract, including nuclear cataract (OR, 3.78; 95% CI, 2.91-4.89), cortical cataract (OR, 3.01; 95% CI, 2.45-3.71), and posterior subcapsular cataract (OR, 5.00; 95% CI, 3.91-6.41). The population attributable risks of cataract surgery related to diabetes and myopia were 17.6% and 19.1%, respectively. CONCLUSIONS: One in 10 Malay, Indian, and Chinese Singaporeans 40 years of age or older underwent cataract surgery in at least 1 eye over 6 years. In Asian populations, diabetes and myopia, 2 well-known factors associated with cataract prevalence, are significant and potentially modifiable factors associated with the need for cataract surgery.

Ancestry, Socioeconomic Status, and Age-Related Cataract in Asians: The Singapore Epidemiology of Eye Diseases Study.

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.

Incidence and progression of reticular drusen in age-related macular degeneration: findings from an older Australian cohort.

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.

Detecting visually significant cataract using retinal photograph-based deep learning.

Age-related cataracts are the leading cause of visual impairment among older adults. Many significant cases remain undiagnosed or neglected in communities, due to limited availability or accessibility to cataract screening. In the present study, we report the development and validation of a retinal photograph-based, deep-learning algorithm for automated detection of visually significant cataracts, using more than 25,000 images from population-based studies. In the internal test set, the area under the receiver operating characteristic curve (AUROC) was 96.6%. External testing performed across three studies showed AUROCs of 91.6-96.5%. In a separate test set of 186 eyes, we further compared the algorithm's performance with 4 ophthalmologists' evaluations. The algorithm performed comparably, if not being slightly more superior (sensitivity of 93.3% versus 51.7-96.6% by ophthalmologists and specificity of 99.0% versus 90.7-97.9% by ophthalmologists). Our findings show the potential of a retinal photograph-based screening tool for visually significant cataracts among older adults, providing more appropriate referrals to tertiary eye centers.

Systemic medications and cortical cataract: the Singapore Epidemiology of Eye Diseases Study.

BACKGROUND/AIMS: To evaluate the association between systemic medications and cortical cataract prevalence in an Asian population. METHODS: The Singapore Epidemiology of Eye Diseases Study recruited 10 033 Chinese, Malay and Indian residents aged 40+ years living in Singapore. Information on medication use was collected at interview using questionnaires. The presence and severity of cortical cataract were assessed from lens photographs using the modified Wisconsin Cataract Grading System. Associations between medications and the presence of cortical cataract were assessed using logistic regression. Associations between medications and greater severity of cortical cataract (none, minimal, early and late) were assessed using ordinal logistic regression. RESULTS: A total of 8965 participants were included, the mean age was 57.6 (SD=9.8) years, and 4555 (50.8%) were women. After adjusting for age, gender, ethnicity, body mass index, smoking status, socioeconomic status, hypertension, hyperlipidaemia, diabetes, duration of diabetes and cardiovascular disease, ACE inhibitors (OR=1.27; 95% CI 1.05 to 1.55), fibrates (OR=1.57; 95% CI 1.05 to 2.35), alpha-glucosidase inhibitors (AGIs) (OR=1.85; 95% CI 1.13 to 3.02) and insulin (OR=1.80; 95% CI 1.11 to 2.93) were significantly associated with the presence of cortical cataract. Further adjusting for concurrent medication use did not alter these associations. Consistently, the four medications were also associated with a greater severity level of cortical cataract. CONCLUSION: ACE inhibitors, fibrates and AGIs were associated with increased prevalence of cortical cataract in this Asian population, independent of the presence of hypertension, hyperlipidaemia and diabetes, respectively. Whether they contribute to the risk of cortical cataract needs confirmation in longitudinal studies.

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.

Evaluating the associations between obesity and age-related cataract: a Mendelian randomization study.

BACKGROUND: The obesity-cataract association has been inconsistently reported. The fat mass and obesity-related (FTO) single-nucleotide polymorphism (SNP) rs9939609 is a major SNP associated with obesity and has been used as an instrumental variable for obesity in a Mendelian randomization (MR) approach. An interaction between the FTO SNP and macronutrient intake for obesity was suggested previously. OBJECTIVE: The aim of this study was to assess the associations between obesity and cataract, using FTO SNP rs9939609 as an instrumental variable in an MR approach, and explore interactions of this SNP with macronutrient intake in relation to risk of cataract in a population-based cohort. METHODS: The Blue Mountains Eye Study (BMES) is a longitudinal population-based study of common eye disease. Of 3654 baseline participants of the BMES (1992-1994), 2334 (75.8% of survivors) and 1952 (76.7% of survivors) were followed 5 and 10 y later. During the 5-y follow-up, 1174 new participants were examined. Cumulative cataract was defined as the presence of cortical, nuclear, or posterior subcapsular (PSC) cataract at any visit, following the Wisconsin Cataract Grading System. Imputed dosage of the FTO SNP rs9939609 was used. Quintiles of macronutrient intake (carbohydrates, protein, fats) were derived from an FFQ. ORs and 95% CIs were estimated using multivariable-adjusted logistic regression models. RESULTS: After multivariable adjustment, there were no associations between BMI and any cataract types in MR models using rs9939609 as an instrumental variable. However, an interaction between rs9939609 and protein intake for PSC cataract risk was suggested (P = 0.03). In analyses stratified by quintiles of protein intake, each minor allele of rs9939609 was associated with increased odds of PSC (OR: 2.14; 95% CI: 1.27, 3.60) in the lowest quintile subgroup only. CONCLUSIONS: Obesity was not causally associated with age-related cataract. However, among persons in the lowest quintile of protein intake, obesity may be associated with PSC cataract.

Retinal vessel caliber and the long-term incidence of age-related cataract: the Blue Mountains Eye Study.

OBJECTIVE: To determine whether local nutritional or ischemic factors are involved in cataract pathogenesis, we aimed to assess whether narrowed retinal vessel caliber predicted the long-term incidence of age-related cataract, as shown in 1 previous report. DESIGN: Population-based cohort study. PARTICIPANTS: The Blue Mountains Eye Study examined 3654 baseline participants (1992-1994), 2335 (75.1% of survivors) after 5 years, and 1952 (75.6% of survivors) after 10 years. METHODS: Retinal vessel caliber was measured from baseline retinal photographs using computer-assisted techniques. Mean arteriolar and venular diameters of each eye were summarized as central retinal arterial (CRAE) and venular (CRVE) equivalents. Cataract was assessed from lens photographs of both eyes using the Wisconsin grading system. MAIN OUTCOME MEASURES: Nuclear cataract was defined as opacity > Wisconsin standard photograph 3, cortical cataract defined as opacity >or=5% of the lens area, and posterior subcapsular (PSC) cataract as any present. Eye-specific data were analyzed using generalized estimating equations. Odds ratios (OR) and 95% confidence intervals (CI) are reported. RESULTS: After adjusting for age, gender, smoking, hypertension, diabetes, body mass index, and inhaled steroid use, reduced incidence of nuclear cataract was associated with the narrowest compared with the widest quintile of CRAE and CRVE (for CRAE: OR, 0.62; 95% CI 0.42-0.92; for CRVE: OR, 0.70; 95% CI, 0.47-1.05) but a higher incidence of PSC cataract (for CRAE: OR, 2.40; 95% CI, 1.34-4.29; for CRVE: OR, 3.17; 95% CI, 1.62-6.20) and cataract surgery (for CRAE: OR, 1.52; 95% CI, 1.06-2.17; for CRVE: OR, 1.58; 95% CI, 1.08-2.32). These associations were not maintained when both CRAE and CRVE were included simultaneously in the same models. Path analysis suggested that age was the most important contributor to nuclear cataract incidence, and CRAE and CRVE, as markers of a latent age-related variable, were only indirectly associated with its incidence (for CRAE: OR, 0.61; 95% CI, 0.41-0.91; for CRVE: OR, 0.62; 95% CI, 0.41-0.94). CONCLUSIONS: Retinal vessel narrowing predicted greater risk of long-term incidence of PSC cataract and cataract surgery, and was indirectly linked to a lower incidence of nuclear cataract. Retinal vessel narrowing could be a marker of age-related factors associated with risk of PSC and nuclear cataract.

Ten-year incidence of age-related cataract and cataract surgery in an older Australian population. The Blue Mountains Eye Study.

PURPOSE: To estimate the 10-year incidence of cataract and cataract surgery in an older Australian population. DESIGN: Prospective population-based study. PARTICIPANTS: Persons at least 49 years old living in 2 postcode areas west of Sydney, Australia. METHODS: Eye examinations were performed at baseline and at 5- and 10-year follow-up visits. Lens photographs were taken and graded by masked graders using the Wisconsin Cataract Grading System. MAIN OUTCOME MEASURES: Incidences of nuclear cataract, cortical cataract, posterior subcapsular cataract (PSC), and cataract surgery. RESULTS: Ten-year person-specific incidences were 36.0% for nuclear cataract, 28.0% for cortical cataract, 9.1% for PSC, and 17.8% for cataract surgery. Corresponding rates were 31.7%, 24.4%, 8.2%, and 14.4%, respectively, in men and 39.3%, 30.8%, 9.8%, and 20.1%, respectively, in women. The incidence for each type of cataract and cataract surgery was positively associated with age (P<0.0001). Women had a significantly higher incidence than men for nuclear cataract (P = 0.04), cortical cataract (P = 0.007), any cataract (P = 0.0006), and cataract surgery (P = 0.03) after adjusting for age. There was no significant gender difference for PSC. The mean age at cataract surgery was 75.8 years, and there was no significant gender difference (P = 0.9). Among persons who developed any cataract, 22% had more than one type and 1.3% had all 3 types present. Nuclear cataract and PSC were significantly associated with visual impairment (visual acuity worse than 20/40). CONCLUSION: Age- and gender-specific cataract incidences in this study were similar to those reported from the U.S. Beaver Dam Eye Study. In this study, 72% of the participants were affected by cataract or had had cataract surgery over the 10-year follow-up period.

Aldose Reductase Polymorphisms, Fasting Blood Glucose, and Age-Related Cortical Cataract.

Purpose: To determine whether there is an association between polymorphisms of the AKR1B1 gene and cortical cataract in the presence of hyperglycemia. Methods: In the second cross section of the Blue Mountains Eye Study (BMES), 3508 participants (2334 at 5-year follow-up and 1174 newly recruited participants) were examined during 1997 to 2000. Cataract was graded from lens photographs using the Wisconsin Cataract Grading System. Fasting blood glucose (FBG) was measured. Continuous imputed dosages of minor alleles of 17 AKR1B1 single nucleotide polymorphisms (SNPs) were assessed for associations with prevalent cortical cataract. Gene-environment interactions between SNPs and FBG were examined. Odds ratios (OR) and 95% confidence intervals (CI) for prevalent cortical cataract were estimated using logistic regression adjusting for age, sex, smoking, hypertension, education, and myopia. A P value of 0.005 was considered statistically significant after correction for 10 independent tests. Replication of significant associations found in the BMES sample was conducted in the Singapore Epidemiology of Eye Diseases (SEED) study (n = 10,033). Results: No polymorphism was associated with prevalent cortical cataract. A significant interaction was observed between rs9640883 and FBG (Pinteraction = 0.004), with increased cortical cataract prevalence associated with rs9640883 minor allele dosage in those with FBG >6.0 mM (strata-specific OR 1.72, 95% CI 1.09-2.72). No similar association was found in participants with normal FBG (OR 0.85, 95% CI 0.69-1.04). This interaction was not evident in the SEED study. Conclusions: The identified interaction between rs9640883 and FBG in relation to cortical cataract was not replicated but may warrant further investigation.

Circulating inflammatory markers and hemostatic factors in age-related maculopathy: a population-based case-control study.

PURPOSE: To examine the relationship between circulating inflammatory markers, hemostatic factors, and age-related maculopathy (ARM). METHODS: A population-based, cross-sectional case-control study drawn from the Blue Mountains Eye Study included 159 early and 38 late ARM cases, and 433 controls matched for age, gender, and smoking. ARM lesions were assessed from retinal photographs according to the Wisconsin ARM grading system. Circulating inflammatory markers (high-sensitivity C-reactive protein [hsCRP], intercellular adhesion molecule [ICAM]-1, and interleukin [IL]-6), white cell count (WCC), and hemostatic factors (fibrinogen, homocysteine, plasminogen activator inhibitor [PAI]-1 and von Willebrand factor [vWF]) were assessed. Age, gender, current smoking, body mass index, hypertension, history of stroke, and cardiovascular events were adjusted for. Adjusted mean levels of each marker were compared between persons with early ARM, those with late ARM, and control subjects, and are presented as probabilities. Adjusted associations with ARM were examined continuously (per SD), and are presented as odds ratios (ORs) and 95% confidence intervals (CIs). Summarizing z scores for inflammation and hemostatic dysfunction were calculated. RESULTS: Increased PAI-1 level was associated with both early (OR 1.2, 95% CI 1.0-1.4 per SD increase) and late ARM (OR 1.3, 95% CI 0.9-1.9 per SD increase). Elevated ICAM-1 level was marginally associated with late ARM (OR 1.3, 95% CI 1.0-1.7 per SD increase). No other significant associations were found between the remaining inflammatory or hemostatic markers and either early or late ARM. Summarized z scores for inflammatory or hemostatic markers also did not suggest any associations. CONCLUSIONS: There was no consistent pattern of association found between ARM and circulating inflammatory markers or hemostatic factors in this population-based case-control study.

Prevalence and associations of enhanced retinal arteriolar light reflex: a new look at an old sign.

PURPOSE: To assess the prevalence, associated risk factors and prognosis (mortality) of the enhanced retinal arteriolar light reflex sign in an older Australian population. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Three thousand six hundred fifty-four participants (82.4% response) ages >/=49 years from Australia's Blue Mountains region. METHODS: Retinal photographs of participants were graded for presence and severity of the enhanced arteriolar light reflex sign by comparison with standard photographs. Associations with systemic factors (subject-specific) and ocular variables (eye-specific) were assessed by logistic regression. Mortality data were obtained using the Australian National Death Index. Hazard ratios were calculated using Cox regression. MAIN OUTCOME MEASURES: Prevalence of enhanced arteriolar light reflex and associations with demographic variables (age, gender), blood pressure, blood parameters, health risk behaviors, cataract, retinal vessel wall signs, retinopathy, and 10-year incident mortality. RESULTS: The enhanced arteriolar light reflex sign was found in 1053 participants (31.7%, including 28.8% graded as mild and 2.9% as marked). Prevalence decreased with age (36.0%, 37.7%, 28.0%, and 18.8% for age groups < 60, 60-69, 70-79 and > or = 80 years, respectively, P(trend)<0.0001); odds ratio (OR) 0.78; and 95% confidence interval (CI) 0.72 to 0.85 per decade. Persons with cataract were less likely to have mildly enhanced light reflex (OR, 0.74; CI 0.64-0.87). After multivariate adjustment, mildly enhanced light reflex was significantly associated with serum glucose (OR 1.11 per SD increase), total cholesterol (OR 1.11), low-density lipoprotein (OR 1.55), triglycerides (OR 1.11), platelets (OR 0.89), and body mass index (OR 1.12). Markedly enhanced light reflex was significantly associated with mean arterial blood pressure (OR 1.24), heavy alcohol consumption (OR 2.66, > or = 40 grams alcohol per day), and serum glucose (OR 1.16). Strong associations were demonstrated between presence of mildly enhanced light reflex and either arteriovenous nicking (OR 3.12) or retinopathy (OR 1.96). There was no association between mildly or markedly enhanced light reflex and either all-cause or vascular mortality. CONCLUSIONS: In this older population, the enhanced retinal arteriolar light reflex sign was a relatively common finding. Although some associations of this sign with vascular risk factors were found, only a marked level of enhanced light reflex was correlated with elevated blood pressure, but not with poor survival.

Prevalence, Risk Factors, and Impact of Undiagnosed Visually Significant Cataract: The Singapore Epidemiology of Eye Diseases Study.

OBJECTIVE: To determine the prevalence, risk factors, and impact of undiagnosed visually significant cataract in an Asian population. METHODS: The Singapore Epidemiology of Eye Diseases is a population-based study where 8,697 adults of Malay, Indian, and Chinese ethnicities aged > 40 years were invited for an eye examination, including lens photograph, to establish cataract diagnosis. Visually significant cataract was defined by Wisconsin Cataract Grading System and a best-corrected visual acuity <20/40 with cataract as the primary cause of vision impairment. Participants were deemed 'undiagnosed' if they had visually significant cataract and reported no prior physician diagnosis of cataract. Visual functioning (VF) was assessed with the VF-11 questionnaire validated using Rasch analysis. RESULTS: Among the 925 participants with visually significant cataract, 636 (68.8%) were unaware of their cataract status. Age-standardized prevalence varied according to ethnicity, with Malays having higher rates than Chinese and Indians. Factors independently associated with having undiagnosed visually significant cataract were: Malay ethnicity, lower educational attainment, in employment, and without a history of diabetes (all P<0.05). In those with undiagnosed visually significant cataract, half had bilateral visual impairment, which was significantly associated with 24.8% poorer visual functioning compared to those with unilateral visual impairment (P<0.001). CONCLUSIONS: Two-thirds of Singaporean adults with visually significant cataract were previously undiagnosed. Half of these cases had bilateral visual impairment and substantially reduced quality of life. Public health strategies targeting elderly patients, such as regular screening for visual impairment and timely referral to ophthalmologists in order to prevent progression to bilateral visual impairment when visual function is compromised are warranted.

Comparison of age-specific cataract prevalence in two population-based surveys 6 years apart.

BACKGROUND: In this study, we aimed to compare age-specific cortical, nuclear and posterior subcapsular (PSC) cataract prevalence in two surveys 6 years apart. METHODS: The Blue Mountains Eye Study examined 3654 participants (82.4% of those eligible) in cross-section I (1992-4) and 3509 participants (75.1% of survivors and 85.2% of newly eligible) in cross-section II (1997-2000, 66.5% overlap with cross-section I). Cataract was assessed from lens photographs following the Wisconsin Cataract Grading System. Cortical cataract was defined if cortical opacity comprised > or = 5% of lens area. Nuclear cataract was defined if nuclear opacity > or = Wisconsin standard 4. PSC was defined if any present. Any cataract was defined to include persons who had previous cataract surgery. Weighted kappa for inter-grader reliability was 0.82, 0.55 and 0.82 for cortical, nuclear and PSC cataract, respectively. We assessed age-specific prevalence using an interval of 5 years, so that participants within each age group were independent between the two surveys. RESULTS: Age and gender distributions were similar between the two populations. The age-specific prevalence of cortical (23.8% in 1st, 23.7% in 2nd) and PSC cataract (6.3%, 6.0%) was similar. The prevalence of nuclear cataract increased slightly from 18.7% to 23.9%. After age standardization, the similar prevalence of cortical (23.8%, 23.5%) and PSC cataract (6.3%, 5.9%), and the increased prevalence of nuclear cataract (18.7%, 24.2%) remained. CONCLUSION: In two surveys of two population-based samples with similar age and gender distributions, we found a relatively stable cortical and PSC cataract prevalence over a 6-year period. The increased prevalence of nuclear cataract deserves further study.

Associations Between Methylenetetrahydrofolate Reductase Polymorphisms, Serum Homocysteine Levels, and Incident Cortical Cataract.

IMPORTANCE: Methylenetetrahydrofolate reductase (MTHFR) polymorphisms have been shown to influence homocysteine levels; homocysteine has been implicated as a cataractogenic stressor. OBJECTIVE: To investigate the associations of MTHFR polymorphisms and serum homocysteine levels with incident cortical cataract in an older population. DESIGN, SETTING, AND PARTICIPANTS: From 1992 to 1994, a population-based cohort study, the Blue Mountains Eye Study, was conducted with 3654 residents (82.4% of eligible participants) of the Blue Mountains region aged 49 years and older. At the second (1997-1999, 5-year follow-up) and third (2002-2004, 10-year follow-up) surveys, 2334 (75.8% of survivors) and 1952 (76.7% of survivors) were examined, respectively. For this report, the second survey serves as baseline when homocysteine levels were assessed, and 5-year incidence of cataract refers to incidence estimated from the second to the third survey. After excluding participants with no follow-up data or DNA or who had previous cortical cataract or cataract surgery, 757 participants were included in gene and environment analyses. This current project on associations with cataract was designed initially March 19, 2013, and completed April 14, 2014. Cataract was assessed using the Wisconsin Cataract Grading system. Two MTHFR polymorphisms, C677T (rs1801133) and A1298C (rs1801131), were included. Serum homocysteine levels were assessed following standard methods. MAIN OUTCOMES AND MEASURES: Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals for incident cortical cataract, after adjusting for age, sex, smoking status, hypertension, diabetes, education, and myopia. Path analysis was performed to explore a possible pathway of MTHFR polymorphisms via homocysteine levels to cortical cataract. RESULTS: The mean (SD) age of the 1726 participants in the Blue Mountains Eye Study 2 cohort with normal homocysteine levels was 68.3 (8.1) years and 73.2 (8.5) years for those with elevated homocysteine levels. Both the C677T polymorphism (CT/TT vs CC: OR = 1.50; 95% CI = 1.01-2.23) and elevated homocysteine levels (>15 µmol/L: OR = 2.24; 95% CI = 1.38-3.63) were independently associated with increased risk of cortical cataract. Path analysis showed that the genetic effect on cortical cataract was partially mediated via homocysteine levels. Combined CT/TT genotypes and elevated homocysteine levels were associated with a 3-fold risk of cortical cataract (OR = 3.74; 95% CI = 1.79-7.80). The synergy index of both exposures was 1.34 (95% CI = 0.44-4.01). CONCLUSIONS AND RELEVANCE: MTHFR polymorphism and elevated homocysteine levels contributed separately and jointly to increased risk of cortical cataract. If these findings are confirmed, homocysteine levels may be a therapeutic target to reduce risk of cortical cataract in persons carrying genetic risk.

Serum homocysteine, vitamin B12, and folate, and the prevalence and incidence of posterior subcapsular cataract.

PURPOSE: We assessed associations between serum levels of homocysteine, vitamin B12, and folate, and the prevalence and 5-year incidence of posterior subcapsular cataract (PSC) in Blue Mountains Eye Study participants. METHODS: We examined 3508 participants aged 49+ years during 1997 to 2000, including 2334 (75.1% of survivors) original and 1174 (85.2% of those eligible) newly recruited subjects. Five years later (2002-2004), 1952 (76.6% of survivors) original participants were re-examined. Detailed examinations, including lens photographs and fasting blood tests, were conducted at both visits. Logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI) after multivariable adjustment. RESULTS: In this population, those with PSC were older, less likely to have higher education, and more likely to have diabetes and myopia. The PSC prevalence was 5.7% (150/2644). Higher levels of homocysteine (per SD; OR, 1.17; 95% CI, 1.00-1.37) and lower levels of folate (per SD; OR, 1.24; 95% CI, 0.99-1.56) were associated with prevalent PSC. There was significant interaction (P < 0.05) between vitamin B12 and homocysteine; for B12 ≥125 pmol/L, 28% higher PSC prevalence was associated with homocysteine (per SD; OR, 1.28; 95% CI, 1.09-1.52); however, for B12 <125 pmol/L, nonsignificant lower PSC prevalence was associated with homocysteine (per SD; OR, 0.16; 95% CI, 0.02-1.57). The 5-year PSC incidence was 5.7% (n = 59/1030) with no significant associations with homocysteine, B12, and folate. CONCLUSIONS: Higher serum homocysteine level was associated with PSC prevalence in this population. Vitamin B12 status seemed to modify this association. Lack of longitudinal association could have resulted from insufficient study power.