Prevalence and risk factors for myopia and other refractive errors in an adult population in southern India.

PURPOSE: To investigate prevalence and risk factors for myopia, hyperopia and astigmatism in southern India. METHODS: Randomly sampled villages were enumerated to identify people aged ≥40 years. Participants were interviewed for socioeconomic and lifestyle factors and attended a hospital-based ophthalmic examination including visual acuity measurement and objective and subjective measurement of refractive status. Myopia was defined as spherical equivalent (SE) worse than -0.75 dioptres (D), hyperopia as SE ≥+1D and astigmatism as cylinder <-0.5. RESULTS: The age-standardised prevalences of myopia, hyperopia and astigmatism were 35.6% (95% CI: 34.7-36.6), 17.0% (95% CI: 16.3-17.8) and 32.6 (29.3-36.1), respectively. Of those with myopia (n = 1490), 70% had advanced cataract. Of these, 79% had presenting visual acuity (VA) less than 6/18 and after best correction, 44% of these improved to 6/12 or better and 27% remained with VA less than 6/18. In multivariable analyses (excluding patients with advanced cataract), increasing nuclear opacity score, current tobacco use, and increasing height were associated with higher odds of myopia. Higher levels of education were associated with increased odds of myopia in younger people and decreased odds in older people. Increasing time outdoors was associated with myopia only in older people. Increasing age and female gender were associated with hyperopia, and nuclear opacity score, increasing time outdoors, rural residence and current tobacco use with lower odds of hyperopia. After controlling for myopia, factors associated with higher odds of astigmatism were age, rural residence, and increasing nuclear opacity score and increasing education with lower odds. CONCLUSIONS: In contrast to high-income settings and in agreement with studies from low-income settings, we found a rise in myopia with increasing age reflecting the high prevalence of advanced cataract.

Mediterranean Diet Score and Its Association with Age-Related Macular Degeneration: The European Eye Study.

PURPOSE: To examine associations between adherence to a Mediterranean diet and prevalence of age-related macular degeneration (AMD) in countries ranging from Southern to Northern Europe. DESIGN: Cross-sectional, population-based epidemiologic study. PARTICIPANTS: Of 5060 randomly sampled people aged 65 years or older from 7 study centers across Europe (Norway, Estonia, United Kingdom, France, Italy, Greece, and Spain), full dietary data were available in 4753. The mean age of participants was 73.2 years (standard deviation, 5.6), and 55% were women. METHODS: Participants underwent an eye examination and digital retinal color photography. The images were graded at a single center. Dietary intake during the previous 12 months was assessed by using a semiquantitative food-frequency questionnaire (FFQ). A previously published Mediterranean Diet Score (MDS) was used to classify participants according to their responses on the FFQ. Multivariable logistic regression was used to investigate the association of the MDS score and AMD, taking account of potential confounders and the multicenter study design. MAIN OUTCOME MEASURES: Images were graded according to the International Classification System for age-related maculopathy and stratified using the Rotterdam staging system into 5 exclusive stages (AMD 0-4) and a separate category of large drusen (≥125 µm). Age-related macular degeneration 4 included neovascular AMD (nvAMD) and geographic atrophy (GA). RESULTS: Increasing MDS was associated with reduced odds of nvAMD in unadjusted and confounder-adjusted analysis. Compared with the lowest MDS adherence (≤4 score), those in the highest category MDS adherence (>6 score) showed lower odds of nvAMD (odds ratio, 0.53; 0.27-1.04; P trend = 0.01). The association with MDS did not differ by Y204H risk allele (P = 0.89). For all early AMD (grade 1-3), there was no relationship with MDS (P trend = 0.9). There was a weak trend (P = 0.1) between MDS and large drusen; those in the highest category of MDS had 20% reduced odds compared with those in the lowest (P = 0.05). CONCLUSIONS: This study adds to the limited evidence of the protective effect of adherence to a Mediterranean dietary pattern in those with late AMD, although it does not support previous reports of a relationship with genetic susceptibility. Interventions to encourage the adoption of the Mediterranean diet should be developed, and methods by which such behavior change can be achieved and maintained investigated.

Associations between Serum Vitamin D and Genetic Variants in Vitamin D Pathways and Age-Related Macular Degeneration in the European Eye Study.

PURPOSE: To study associations between early and late age-related macular degeneration (AMD) and neovascular AMD (nvAMD) with serum 25-hydroxy vitamin D (25(OH)D) and genetic variants in vitamin D pathway genes. DESIGN: Population-based, cross-sectional study in a random sample aged 65 years or older from 7 European countries. PARTICIPANTS: Of 4753 participants, 4496 (2028 men and 2468 women), with a mean age of 73 years, provided a blood sample; 2137 had no signs of AMD, 2209 had early AMD, and 150 had late AMD, of whom 104 had nvAMD. METHODS: Participants were interviewed to determine smoking and alcohol use, sunlight exposure, and diet; underwent fundus photography. Fundus images were graded using the International Classification System for Age-Related Maculopathy. The 25(OH)D was measured by liquid chromatography-tandem mass spectrometry and categorized as deficient (<30 nmol/l), insufficient (30-50 nmol/l), or adequate (≥50 nmol/l). Genotyping was performed on a subsample of 1284 AMD cases and controls for 93 single nucleotide polymorphisms (SNPs) from 7 genes. Associations were investigated by linear or logistic regression adjusted for potential confounders. MAIN OUTCOME MEASURES: Adjusted odds ratio (OR) for 3 outcomes (early AMD, late AMD, nvAMD). RESULTS: No linear association was found with 25(OH)D and early or late AMD or nvAMD. There was no association between insufficient or deficient status with early or late AMD. Deficient status was associated with nvAMD (adjusted OR, 1.27; 95% confidence interval, 1.1-1.45; P < 0.0001). Significant (P < 0.05) associations with 25(OH)D were found for SNPs in genes GC, VDR, CYP2R1, and CYP27B1. Two SNPs (VDR) were associated with early AMD, 4 SNPs (RXRA) and 1 SNP (VDR) were associated with nvAMD, and 1 SNP (RXRA), 2 SNPs (VDR), and 1 SNP (CYP2R1) were associated with late AMD. After Bonferroni correction, no SNPs were associated with early AMD, late AMD, or nvAMD. CONCLUSIONS: Deficiency in 25(OH)D was associated with nvAMD, but the adjusted OR was small, and we cannot exclude residual confounding. The hypothesis of a causal association of vitamin D with AMD is not supported by clear evidence for an association of vitamin D SNPs with early AMD, late AMD, or nvAMD.

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future.

PURPOSE: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. DESIGN: Meta-analysis of prevalence data. PARTICIPANTS: A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. METHODS: AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). MAIN OUTCOME MEASURES: Prevalence of early and late AMD, BCVA, and number of AMD cases. RESULTS: Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%-5.0%) in those aged 55-59 years to 17.6% (95% CI 13.6%-21.5%) in those aged ≥85 years; for late AMD these figures were 0.1% (95% CI 0.04%-0.3%) and 9.8% (95% CI 6.3%-13.3%), respectively. We observed a decreasing prevalence of late AMD after 2006, which became most prominent after age 70. Prevalences were similar for gender across all age groups except for late AMD in the oldest age category, and a trend was found showing a higher prevalence of CNV in Northern Europe. After 2006, fewer eyes and fewer ≥80-year-old subjects with CNV were visually impaired (P = 0.016). Projections of AMD showed an almost doubling of affected persons despite a decreasing prevalence. By 2040, the number of individuals in Europe with early AMD will range between 14.9 and 21.5 million, and for late AMD between 3.9 and 4.8 million. CONCLUSION: We observed a decreasing prevalence of AMD and an improvement in visual acuity in CNV occuring over the past 2 decades in Europe. Healthier lifestyles and implementation of anti-vascular endothelial growth factor treatment are the most likely explanations. Nevertheless, the numbers of affected subjects will increase considerably in the next 2 decades. AMD continues to remain a significant public health problem among Europeans.

Polymorphisms in sodium-dependent vitamin C transporter genes and plasma, aqueous humor and lens nucleus ascorbate concentrations in an ascorbate depleted setting.

We have previously reported low concentrations of plasma ascorbate and low dietary vitamin C intake in the older Indian population and a strong inverse association of these with cataract. Little is known about ascorbate levels in aqueous humor and lens in populations habitually depleted of ascorbate and no studies in any setting have investigated whether genetic polymorphisms influence ascorbate levels in ocular tissues. Our objectives were to investigate relationships between ascorbate concentrations in plasma, aqueous humor and lens and whether these relationships are influenced by Single Nucleotide Polymorphisms (SNPs) in sodium-dependent vitamin C transporter genes (SLC23A1 and SLC23A2). We enrolled sixty patients (equal numbers of men and women, mean age 63 years) undergoing small incision cataract surgery in southern India. We measured ascorbate concentrations in plasma, aqueous humor and lens nucleus using high performance liquid chromatography. SLC23A1 SNPs (rs4257763, rs6596473) and SLC23A2 SNPs (rs1279683 and rs12479919) were genotyped using a TaqMan assay. Patients were interviewed for lifestyle factors which might influence ascorbate. Plasma vitamin C was normalized by a log10 transformation. Statistical analysis used linear regression with the slope of the within-subject associations estimated using beta (ß) coefficients. The ascorbate concentrations (µmol/L) were: plasma ascorbate, median and inter-quartile range (IQR), 15.2 (7.8, 34.5), mean (SD) of aqueous humor ascorbate, 1074 (545) and lens nucleus ascorbate, 0.42 (0.16) (µmol/g lens nucleus wet weight). Minimum allele frequencies were: rs1279683 (0.28), rs12479919 (0.30), rs659647 (0.48). Decreasing concentrations of ocular ascorbate from the common to the rare genotype were observed for rs6596473 and rs12479919. The per allele difference in aqueous humor ascorbate for rs6596473 was -217 µmol/L, p < 0.04 and a per allele difference in lens nucleus ascorbate of -0.085 µmol/g, p < 0.02 for rs12479919. The ß coefficients for the regression of log10 plasma ascorbate on aqueous humor ascorbate were higher for the GG genotype of rs6596473: GG, ß = 1460 compared to carriage of the C allele, CG, ß = 1059, CC, ß = 1132, p interaction = 0.1. In conclusion we found that compared to studies in well-nourished populations, ascorbate concentrations in the plasma, aqueous humor and lens nucleus were low. We present novel findings that polymorphisms in SLC23A1/2 genes influenced ascorbate concentration in aqueous humor and lens nucleus.

ARMS2 increases the risk of early and late age-related macular degeneration in the European Eye Study.

OBJECTIVE: To study associations between severity stages of early and late age-related macular degeneration (AMD) and genetic variations in age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) and to investigate potential interactions between smoking and ARMS2. DESIGN: Population-based, cross-sectional European Eye Study in 7 countries in Europe. PARTICIPANTS: Four thousand seven hundred fifty participants, 65 years of age and older, recruited through random sampling. METHODS: Participants were classified on the basis of the more severely affected eye into 5 mutually exclusive AMD severity stages ranging from no AMD, 3 categories of early AMD, and late AMD. History of cigarette smoking was available and allowed classification into never, former, and current smokers, with the latter 2 groups combined into a single category of ever smokers for analysis. Genotyping was performed for single nucleotide polymorphisms rs10490924 and rs4146894 in ARMS2 and rs1061170 in CFH. Associations were analyzed by logistic regression. MAIN OUTCOME MEASURES: Odds ratios (ORs) for stage of AMD associated with genetic variations in ARMS2 and CFH and interactions between ARMS2 and smoking status. RESULTS: Early AMD was present in 36.4% and late AMD was present in 3.3% of participants. Data on both genotype and AMD were available for 4276 people. The ORs for associations between AMD stage and ARMS2 increased monotonically with more severe stages of early AMD and were altered little by adjustment for potential confounders. Compared with persons with no AMD, carriers of the TT genotype for rs10490924 in ARMS2 had a 10-fold increase in risk of late AMD (P<3 × 10(-20)). The ORs for associations with CFH were similar for stage 3 early AMD and late AMD. Interactions between rs10490924 in ARMS2 and smoking status were significant in both unadjusted and adjusted models (P = 0.001). The highest risk was observed in those doubly homozygous for rs10490924 and rs1061170 in CFH (OR, 62.3; 95% confidence interval, 16-242), with P values for trend ranging from 0.03 (early AMD, stage 1) to 1 × 10(-26) (late AMD). CONCLUSIONS: A strong association was demonstrated between all stages of AMD and genetic variation in ARMS2, and a significant gene-environment interaction with cigarette smoking was confirmed.

Methods for a population-based Comprehensive Eye care Workload Assessment (CEWA) study in Southern India.

Eye care programs, in developing countries, are often planned using the prevalence of blindness and visual impairment, often estimated from Rapid Assessment of Avoidable Blindness (RAAB) surveys. A limitation of this planning approach is that it ignores the annual overall eye care requirements for a given population. Moreover, targets set are arbitrary, often influenced by capacity rather than need. To address this lacunae, we implemented a novel study design to estimate the annual need for comprehensive eye care in a 1.2 million populations. We conducted a population-based longitudinal study in Theni district, Tamil Nadu, India. All permanent residents of all ages were included. We conducted the study in three phases, (i) household-level enumeration and enrollment, (ii) basic eye examination (BEE) at household one-year post-enrollment, and (iii) assessment of eye care utilization and full eye examination (FEE) at central locations. All people aged 40 years and above were invited to the FEE. Those aged <40 years were invited to the FEE if indicated. In the main study, we enrolled 24,327 subjects (58% aged below 40 years and 42% aged 40 years and above). Of those less than 40 years, 72% completed the BEE, of whom 20% were referred for FEE at central location. Of the people aged ≥40 years, 70% underwent FEE. Our study design provides insights for appropriate long-term public health intervention planning, resource allocation, effective service delivery, and designing of eye care services for resource-limited settings.

Associations between aspirin use and aging macula disorder: the European Eye Study.

OBJECTIVE: To study associations between aspirin use and early and late aging macula disorder (AMD). DESIGN: Population-based cross-sectional European Eye Study in 7 centers from northern to southern Europe. PARTICIPANTS: In total, 4691 participants 65 years of age and older, collected by random sampling. METHODS: Aspirin intake and possible confounders for AMD were ascertained by a structured questionnaire. Ophthalmic and basic systemic measurements were performed in a standardized way. The study classified AMD according to the modified International Classification System on digitized fundus images at 1 grading center. Nonfasting blood samples were analyzed in a single laboratory. Associations were analyzed by logistic regression. MAIN OUTCOME MEASURES: Odds ratios (ORs) for AMD in aspirin users. RESULTS: Early AMD was present in 36.4% of the participants and late AMD was present in 3.3% of participants. Monthly aspirin use was reported by 1931 (41.2%), at least once weekly by 7%, and daily use by 17.3%. For daily aspirin users, the ORs, adjusted for potential confounders, showed a steady increase with increasing severity of AMD grades. These were: grade 1, 1.26 (95% confidence interval [CI], 1.08-1.46; P<0.001); grade 2, 1.42 (95% CI, 1.18-1.70), and wet late AMD, 2.22 (95% CI, 1.61-3.05). CONCLUSIONS: Frequent aspirin use was associated with early AMD and wet late AMD, and the ORs rose with increasing frequency of consumption. This interesting observation warrants further evaluation of the associations between aspirin use and AMD. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Evidence of association of APOE with age-related macular degeneration: a pooled analysis of 15 studies.

Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status has been reported. We present a pooled analysis (n = 21,160) demonstrating associations between late AMD and APOε4 (odds ratio [OR] = 0.72 per haplotype; confidence interval [CI]: 0.65-0.74; P = 4.41×10(-11) ) and APOε2 (OR = 1.83 for homozygote carriers; CI: 1.04-3.23; P = 0.04), following adjustment for age group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR = 1.54; CI: 1.38-1.72; P = 2.8×10(-15) ) and atrophic (OR = 1.38; CI: 1.18-1.61; P = 3.37×10(-5) ) AMD but not early AMD (OR = 0.94; CI: 0.86-1.03; P = 0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyond ε2 and ε4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology.

Variations in apolipoprotein E frequency with age in a pooled analysis of a large group of older people.

Variation in the apolipoprotein E gene (APOE) has been reported to be associated with longevity in humans. The authors assessed the allelic distribution of APOE isoforms ε2, ε3, and ε4 among 10,623 participants from 15 case-control and cohort studies of age-related macular degeneration (AMD) in populations of European ancestry (study dates ranged from 1990 to 2009). The authors included only the 10,623 control subjects from these studies who were classified as having no evidence of AMD, since variation within the APOE gene has previously been associated with AMD. In an analysis stratified by study center, gender, and smoking status, there was a decreasing frequency of the APOE ε4 isoform with increasing age (χ(2) for trend = 14.9 (1 df); P = 0.0001), with a concomitant increase in the ε3 isoform (χ(2) for trend = 11.3 (1 df); P = 0.001). The association with age was strongest in ε4 homozygotes; the frequency of ε4 homozygosity decreased from 2.7% for participants aged 60 years or less to 0.8% for those over age 85 years, while the proportion of participants with the ε3/ε4 genotype decreased from 26.8% to 17.5% across the same age range. Gender had no significant effect on the isoform frequencies. This study provides strong support for an association of the APOE gene with human longevity.

Treatment of hypertension in patients 80 years of age or older.

BACKGROUND: Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear. It has been suggested that antihypertensive therapy may reduce the risk of stroke, despite possibly increasing the risk of death. METHODS: We randomly assigned 3845 patients from Europe, China, Australasia, and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide (sustained release, 1.5 mg) or matching placebo. The angiotensin-converting-enzyme inhibitor perindopril (2 or 4 mg), or matching placebo, was added if necessary to achieve the target blood pressure of 150/80 mm Hg. The primary end point was fatal or nonfatal stroke. RESULTS: The active-treatment group (1933 patients) and the placebo group (1912 patients) were well matched (mean age, 83.6 years; mean blood pressure while sitting, 173.0/90.8 mm Hg); 11.8% had a history of cardiovascular disease. Median follow-up was 1.8 years. At 2 years, the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group. In an intention-to-treat analysis, active treatment was associated with a 30% reduction in the rate of fatal or nonfatal stroke (95% confidence interval [CI], -1 to 51; P=0.06), a 39% reduction in the rate of death from stroke (95% CI, 1 to 62; P=0.05), a 21% reduction in the rate of death from any cause (95% CI, 4 to 35; P=0.02), a 23% reduction in the rate of death from cardiovascular causes (95% CI, -1 to 40; P=0.06), and a 64% reduction in the rate of heart failure (95% CI, 42 to 78; P<0.001). Fewer serious adverse events were reported in the active-treatment group (358, vs. 448 in the placebo group; P=0.001). CONCLUSIONS: The results provide evidence that antihypertensive treatment with indapamide (sustained release), with or without perindopril, in persons 80 years of age or older is beneficial. (ClinicalTrials.gov number, NCT00122811 [ClinicalTrials.gov].).

Prevalence of cataract in an older population in India: the India study of age-related eye disease.

PURPOSE: To describe the prevalence of cataract in older people in 2 areas of north and south India. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: Randomly sampled villages were enumerated to identify people aged ≥ 60 years. Of 7518 enumerated people, 78% participated in a hospital-based ophthalmic examination. METHODS: The examination included visual acuity measurement, dilatation, and anterior and posterior segment examination. Digital images of the lens were taken and graded by type and severity of opacity using the Lens Opacity Classification System III (LOCS III). MAIN OUTCOME MEASURES: Age- and gender-standardized prevalence of cataract and 95% confidence intervals (CIs). We defined type of cataract based on the LOCS III grade in the worse eye of: ≥ 4 for nuclear cataract, ≥ 3 for cortical cataract, and ≥ 2 for posterior subcapsular cataract (PSC). Any unoperated cataract was based on these criteria or ungradable dense opacities. Any cataract was defined as any unoperated or operated cataract. RESULTS: The prevalence of unoperated cataract in people aged ≥ 60 was 58% in north India (95% CI, 56-60) and 53% (95% CI, 51-55) in south India (P = 0.01). Nuclear cataract was the most common type: 48% (95% CI, 46-50) in north India and 38% (95% CI, 37-40) in south India (P<0.0001); corresponding figures for PSC were 21% (95% CI, 20-23) and 17% (95% CI, 16-19; P = 0.003), respectively, and for cortical cataract 7.6% (95% CI, 7-9) and 10.2% (95% CI, 9-11; P<0.004). Bilateral aphakia/pseudophakia was slightly higher in the south (15.5%) than in the north (13.2%; P<0.03). The prevalence of any cataracts was similar in north (73.8%) and south India (71.8%). The prevalence of unoperated cataract increased with age and was higher in women than men (odds ratio [OR], 1.8). Aphakia/pseudophakia was also more common in women, either unilateral (OR, 1.2; P<0.02) or bilateral (OR, 1.3; P<0.002). CONCLUSIONS: We found high rates of unoperated cataract in older people in north and south India. Posterior subcapsular cataract was more common than in western studies. Women had higher rates of cataract, which was not explained by differential access to surgery.

Inverse association of vitamin C with cataract in older people in India.

OBJECTIVE: To examine the association between vitamin C and cataract in the Indian setting. DESIGN: Population-based cross-sectional analytic study. PARTICIPANTS: A total of 5638 people aged ≥60 years. METHODS: Enumeration of randomly sampled villages in 2 areas of north and south India to identify people aged ≥60 years. Participants were interviewed for socioeconomic and lifestyle factors (tobacco, alcohol, household cooking fuel, work, and diet); attended a clinical examination, including lens photography; and provided a blood sample for antioxidant analysis. Plasma vitamin C was measured using an enzyme-based assay in plasma stabilized with metaphosphoric acid, and other antioxidants were measured by reverse-phase high-pressure liquid chromatography. MAIN OUTCOME MEASURES: Cataract and type of cataract were graded from digital lens images using the Lens Opacity Classification System III (LOCS III), and cataract was classified from the grade in the worse eye of ≥4 for nuclear cataract, ≥3 for cortical cataract, and ≥2 for posterior subcapsular cataract (PSC). Any cataract was defined as any unoperated or operated cataract. RESULTS: Of 7518 enumerated people, 5638 (75%) provided data on vitamin C, antioxidants, and potential confounders. Vitamin C was inversely associated with cataract (adjusted odds ratio [OR] for highest to lowest quartile = 0.61; 95% confidence interval (CI), 0.51-0.74; P=1.1×10(-6)). Inclusion of other antioxidants in the model (lutein, zeaxanthin, retinol, ß-carotene, and α-tocopherol) made only a small attenuation to the result (OR 0.68; 95% CI, 0.57-0.82; P < 0.0001). Similar results were seen with vitamin C by type of cataract: nuclear cataract (adjusted OR 0.66; CI, 0.54-0.80; P < 0.0001), cortical cataract (adjusted OR 0.70; CI, 0.54-0.90; P < 0.002), and PSC (adjusted OR 0.58; CI, 0.45-0.74; P < 0.00003). Lutein, zeaxanthin, and retinol were significantly inversely associated with cataract, but the associations were weaker and not consistently observed by type of cataract. Inverse associations were also observed for dietary vitamin C and cataract. CONCLUSIONS: We found a strong association with vitamin C and cataract in a vitamin C-depleted population. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

A randomised controlled trial investigating the effect of vitamin B12 supplementation on neurological function in healthy older people: the Older People and Enhanced Neurological function (OPEN) study protocol [ISRCTN54195799].

BACKGROUND: Vitamin B12 deficiency is common in older people and the prevalence increases with age. Vitamin B12 deficiency may present as macrocytic anaemia, subacute combined degeneration of the spinal cord, or as neuropathy, but is often asymptomatic in older people. The diagnosis and indications for treatment are clear for individuals with low plasma levels of vitamin B12 in the setting of megaloblastic anaemia and neuropathy, but the relevance of treatment of vitamin B12 deficiency in the absence of such clinical signs is uncertain. METHODS: The aim of the present study is to assess whether dietary supplementation with crystalline vitamin B12 will improve electrophysiological indices of neurological function in older people who have biochemical evidence of vitamin B12 insufficiency in the absence of anaemia. To test this hypothesis we designed a randomized double-blind placebo-controlled trial involving 200 older people aged 75 years or greater who were randomly allocated to receive either a daily oral tablet containing 1 mg vitamin B12 or a matching placebo tablet. The primary outcome assessed at 12 months is change in electrophysiological indices of peripheral and central neurosensory responses required for mobility and sensory function. We here report the detailed study protocol. CONCLUSIONS: In view of the high prevalence of vitamin B12 deficiency in later life, the present trial could have considerable significance for public health.

Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract.

Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h2 = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P = 2.8 × 10-16) with nuclear cataract and identified five new loci associated with this disease: SOX2-OT (rs9842371, P = 1.7 × 10-19), TMPRSS5 (rs4936279, P = 2.5 × 10-10), LINC01412 (rs16823886, P = 1.3 × 10-9), GLTSCR1 (rs1005911, P = 9.8 × 10-9), and COMMD1 (rs62149908, P = 1.2 × 10-8). The results suggest a strong link of age-related nuclear cataract with congenital cataract and eye development genes, and the importance of common genetic variants in maintaining crystalline lens integrity in the aging eye.

CKD and mortality risk in older people: a community-based population study in the United Kingdom.

BACKGROUND: The prevalence of chronic kidney disease (CKD) increases with age; however, the prognostic significance in older people is uncertain. This study aims to determine the association of CKD with all-cause and cardiovascular mortality in community-dwelling older people 75 years and older. STUDY DESIGN: Cohort study of people 75 years and older recruited in 1994 to 1999 to 1 arm of a trial of multidimensional health assessment with mortality follow-up. SETTING & PARTICIPANTS: 53 general practices in Great Britain. 15,336 (73%) of those eligible participated. 13,177 (86%) had serum creatinine measured at baseline. MAIN FACTOR: Estimated glomerular filtration rate (eGFR). OUTCOMES: All-cause and cardiovascular mortality. MEASUREMENTS: eGFR derived from serum creatinine level using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation in milliliters per minute per 1.73 m(2); dipstick proteinuria. Mortality by linkage to national death registration and death certification. RESULTS: After a median follow-up of 7.3 years (interquartile range, 5.0), 7,633 (58%) had died, 42% of cardiovascular causes. In the first 2 years of follow-up, adjusted hazard ratios for all-cause mortality in eGFR bands of 45 to 59, 30 to 44, and less than 30 compared with eGFR greater than 60 mL/min/1.73 m(2) were 1.13 (95% confidence interval, 0.93 to 1.37), 1.69 (95% confidence interval, 1.26 to 2.28), and 3.87 (95% confidence interval, 2.78 to 5.38) in men and 1.14 (95% confidence interval, 0.93 to 1.40), 1.33 (95% confidence interval, 1.06 to 1.68), and 2.44 (95% confidence interval, 1.68 to 3.56) in women, respectively. Hazard ratios were greater for cardiovascular mortality and lower after 2 years. Dipstick proteinuria was independently associated with all-cause, but not cardiovascular, mortality risk in both sexes. LIMITATIONS: Single serum creatinine measurement, no calibration of serum creatinine, MDRD Study equation not validated in older people. CONCLUSION: As kidney function decreases, there is a graded and independent increase in all-cause and cardiovascular mortality risk in older people 75 years and older, especially in men and those with eGFR less than 45 mL/min/1.73 m(2). Dipstick proteinuria did not add to cardiovascular mortality risk in this elderly population. In older people, identification and management of CKD should prioritize the smaller numbers with more severe CKD.

Effectiveness of Teleretinal Imaging-Based Hospital Referral Compared With Universal Referral in Identifying Diabetic Retinopathy: A Cluster Randomized Clinical Trial.

Importance: Studies in high-income countries provide limited evidence from randomized clinical trials on the benefits of teleretinal screening to identify diabetic retinopathy (DR). Objective: To evaluate the effectiveness of teleretinal-screening hospital referral (TR) compared with universal hospital referral (UR) in people with diabetes. Design, Setting, and Participants: A cluster randomized clinical trial of 8 diabetes clinics within 10 km from Aravind Eye Hospital (AEH), Madurai, India, was conducted. Participants included 801 patients older than 50 years. The study was conducted from May 21, 2014, to February 7, 2015; data analysis was performed from March 12 to June 16, 2015. Interventions: In the TR cohort, nonmydriatic, 3-field, 45° retinal images were remotely graded by a retinal specialist and patients with DR, probable DR, or ungradable images were referred to AEH for a retinal examination. In the UR cohort, all patients were referred for a retinal examination at AEH. Main Outcomes and Measures: Hospital-diagnosed DR. Results: Of the 801 participants, 401 were women (50.1%) (mean [SD] age, 60.0 [7.3] years); mean diabetes duration was 8.6 (6.6) years. In the TR cohort, 96 of 398 patients (24.1%) who underwent teleretinal imaging were referred with probable DR (53 [13.3%]) or nongradable images (43 [10.8%]). Hospital attendance at AEH was proportionately higher with TR (54 of 96 referred [56.3%]) compared with UR (150 of 400 referred [37.5%]). The intention-to-treat analysis based on all patients eligible for referral in each arm showed that proportionately more patients with TR (36 of 96 [37.5]%) were diagnosed with DR compared with UR (50 of 400 [12.5%]) (unadjusted risk ratio [RR], 3.00; 95% CI, 2.01-4.48). These results were little changed by inclusion of covariates (RR, 2.72; 95% CI, 1.90-3.91). The RR was lower in the per-protocol analysis based on all patients who adhered to referral (covariate-adjusted RR, 1.75; 95% CI, 1.12-2.74). Diagnoses of DR were predominantly mild or moderate nonproliferative DR (36 in TR and 43 in UR). In the UR arm, there were 4 cases of severe nonproliferative DR and 2 cases of proliferative DR. Age (RR, 0.98; 95% CI, 0.95-0.99), female sex (RR, 0.79; 95% CI, 0.64-0.98), and hypertension diagnosis (RR, 0.81; 95% CI, 0.68-0.95) were factors associated with lower attendance. Those with higher secondary educational level or more were twice as likely to attend (RR, 2.00; 95% CI, 1.32-3.03). Conclusions and Relevance: The proportionate yield of DR cases was higher in the TR arm, confirming the potential benefit, at least in the setting of eye hospitals in India, of a targeted referral approach using teleretinal screening to identify patients with DR. Trial Registration: ClinicalTrials.gov identifier: NCT02085681.

Genetic variants in a sodium-dependent vitamin C transporter gene and age-related cataract.

BACKGROUND: Cataract is a major health burden in many countries and a significant problem in India. While observational studies show lower cataract risk with increasing dietary or plasma vitamin C, randomised controlled trials of supplements have been negative. Genetic variants in vitamin C transporter proteins (SLC23A1), especially rs33972313, may provide evidence on a causal association of vitamin C with cataract. METHODS: We used data from a randomly selected population-based study in people aged 60 years and above in north and south India. Of 7518 sampled, 5428 (72%) were interviewed for socioeconomic and lifestyle factors, attended hospital for lens imaging and blood collection and were subsequently genotyped for rs33972313 and rs6596473. Mixed or pure types of cataract were graded by the Lens Opacity Classification System III as nuclear (2404), cortical (494) or posterior subcapsular cataract (PSC) (1026); 1462 had no significant cataract and no history of cataract surgery and 775 had bilateral aphakia/pseudophakia. RESULTS: rs33972313 was associated with cortical (OR 2.16; 95% CI 1.34 to 3.49, p=0.002) and PSC (OR 1.68; 95% CI 1.06 to 2.65, p=0.03) but not with nuclear cataract. In analyses of pure cataracts, associations were found only between rs33972313 and pure cortical cataracts (OR 2.29; 95% CI 1.12 to 4.65, p=0.03) and with a standardised cortical opacity score. There was no association with rs6596473 and any cataract outcomes. CONCLUSIONS: Using an established genetic variant as a proxy for lifetime ascorbate concentrations, our results support a causal association of vitamin C with cataract.

Cardiovascular disease and hypertension are strong risk factors for choroidal neovascularization.

PURPOSE: To investigate the association of cardiovascular risk factors and inflammatory markers with neovascular age-related macular degeneration (AMD). DESIGN: Cross-sectional case-control study. PARTICIPANTS: Of the 410 of the >/=65-year-old community sample invited to attend, 205 participated (50% response rate). Of the 215 clinic attendees who were invited to participate, 212 agreed to take part (98% response rate). A diagnosis of neovascular AMD in at least one eye was made in 193 clinic attendees and 2 of the community sample. METHODS: Clinic and community participants underwent a detailed ophthalmic examination with fundus imaging, were interviewed for assessment of putative risk factors, and provided a blood sample. Analysis included levels of serum lipids, intercellular adhesion molecule 1 (ICAM), vascular cellular adhesion molecule (VCAM), and C-reactive protein (CRP). All participants were classified by fundus image grading on the basis of the eye with more severe AMD features. MAIN OUTCOME MEASURE: Neovascular AMD. RESULTS: There were 195 participants with choroidal neovascularization in at least one eye, 97 nonneovascular AMD participants, and 115 controls (no drusen or pigmentary irregularities in either eye). In confounder-adjusted logistic regression, a history of cardiovascular disease was strongly associated with neovascular AMD (odds ratio [OR], 7.53; 95% confidence interval [CI], 2.78-20.41). Cigarette smoking (OR, 3.71; 95% CI, 1.25-11.06), being in the highest quartile of body mass index (OR, 3.82; 95% CI, 1.22-12.01), stage 2 hypertension (OR, 3.21; 95% CI, 1.14-8.98), and being in the highest quartile of serum cholesterol (OR, 4.66; 95% CI, 1.35-16.13) were positively associated with neovascular AMD. There was no association between AMD status and serum CRP, ICAM, or VCAM. CONCLUSIONS: Our results suggest that cardiovascular disease plays an etiological role in the development of choroidal neovascularization in a proportion of older adults and highlight the importance of control of blood pressure and cholesterol, avoidance of smoking, and maintenance of a normal body weight.