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Objective To study the prevalence of and associated factors for cognitive impairment and dementia in community dwelling Chinese from Singapore. Methods This study includes Chinese subjects from the Epidemiology of Dementia in Singapore (EDIS) study, aged ≥60 years, who underwent comprehensive examinations, including cognitive screening with the locally validated Abbreviated Mental Test and Progressive Forgetfulness Questionnaire. Screen positive participants subsequently underwent extensive neuropsychological testing and cerebral MRI. Cognitive impairment no dementia (CIND) and dementia were diagnosed according to internationally accepted criteria. The prevalence of cognitive impairment and dementia were computed per 5 year age categories and gender. To examine the relationship between baseline associated factors and cognitive impairment, we used logistic regression models to compute odd ratios with 95% CI. Results 1538 Chinese subjects, aged ≥60 years, underwent cognitive screening: 171 (15.2%) were diagnosed with any cognitive impairment, of whom 84 were CIND mild, 80 CIND moderate and seven had dementia. The overall age adjusted prevalence of CIND mild was 7.2%; CIND moderate/dementia was 7.9%. The prevalence increased with age, from 5.9% in those aged 60–64 years to 31.3% in those aged 75–79 years and 44.1% in those aged ≥80 years. Multivariate analysis revealed age, diabetes and hyperlipidaemia to be independently associated with cognitive impairment. Conclusions In present study, the overall prevalence of cognitive impairment and dementia in Chinese was 15.2%, which is in the same range as the prevalence reported in Caucasian and other Asian populations.

Introduction:C-reactive protein (CRP) levels are associated with cardiovascular disease and systemic inflammation. We assessed whether CRP-associated loci were associated with serum CRP and retinal markers of microvascular disease, in Asian populations.Methods:Genome-wide association analysis (GWAS) for serum CRP was performed in East-Asian Chinese (N = 2,434) and Malays (N = 2,542) and South-Asian Indians (N = 2,538) from Singapore. Leveraging on GWAS data, we assessed, in silico, association levels among the Singaporean datasets for 22 recently identified CRP-associated loci. At loci where directional inconsistencies were observed, quantification of inter-ethnic linkage disequilibrium (LD) difference was determined. Next, we assessed association for a variant at CRP and retinal vessel traits [central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE)] in a total of 24,132 subjects of East-Asian, South-Asian and European ancestry.Results:Serum CRP was associated with SNPs in/near APOE, CRP, HNF1A and LEPR (p-values ≤4.7×10-8) after meta-analysis of Singaporean populations. Using a candidate-SNP approach, we further replicated SNPs at 4 additional loci that had been recently identified to be associated with serum CRP (IL6R, GCKR, IL6 and IL1F10) (p-values ≤0.009), in the Singaporean datasets. SNPs from these 8 loci explained 4.05% of variance in serum CRP. Two SNPs (rs2847281 and rs6901250) were detected to be significant (p-value ≤0.036) but with opposite effect directions in the Singaporean populations as compared to original European studies. At these loci we did not detect significant inter-population LD differences. We further did not observe a significant association between CRP variant and CRVE or CRAE levels after meta-analysis of all Singaporean and European datasets (p-value >0.058).Conclusions:Common variants associated with serum CRP, first detected in primarily European studies, are also associated with CRP levels in East-Asian

Background: Mild retinopathy (microaneurysms or dot-blot hemorrhages) is observed in persons without diabetes or hypertension and may reflect microvascular disease in other organs. We conducted a genome-wide association study (GWAS) of mild retinopathy in persons without diabetes. Methods: A working group agreed on phenotype harmonization, covariate selection and analytic plans for within-cohort GWAS. An inverse-variance weighted fixed effects meta-analysis was performed with GWAS results from six cohorts of 19,411 Caucasians. The primary analysis included individuals without diabetes and secondary analyses were stratified by hypertension status. We also singled out the results from single nucleotide polymorphisms (SNPs) previously shown to be associated with diabetes and hypertension, the two most common causes of retinopathy. Results: No SNPs reached genome-wide significance in the primary analysis or the secondary analysis of participants with hypertension. SNP, rs12155400, in the histone deacetylase 9 gene (HDAC9) on chromosome 7, was associated with retinopathy in analysis of participants without hypertension, 21.360.23 (beta 6 standard error), p=6.661029. Evidence suggests this was a false positive finding. The minor allele frequency was low (,2%), the quality of the imputation was moderate (r2 ,0.7), and no other common variants in the HDAC9 gene were associated with the outcome. SNPs found to be associated with diabetes and hypertension in other GWAS were not associated with retinopathy in persons without diabetes or in subgroups with or without hypertension. Conclusions: This GWAS of retinopathy in individuals without diabetes showed little evidence of genetic associations. Further studies are needed to identify genes associated with these signs in order to help unravel novel pathways and determinants of microvascular diseases.

Narrow arterioles in the retina have been shown to predict hypertension as well as other vascular diseases, likely through an increase in the peripheral resistance of the microcirculatory flow. In this study, we performed a genome-wide association study in 18,722 unrelated individuals of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the Blue Mountain Eye Study, to identify genetic determinants associated with variations in retinal arteriolar caliber. Retinal vascular calibers were measured on digitized retinal photographs using a standardized protocol. One variant (rs2194025 on chromosome 5q14 near the myocyte enhancer factor 2C MEF2C gene) was associated with retinal arteriolar caliber in the meta-analysis of the discovery cohorts at genome-wide significance of P-value < 5 x 10(-8) This variant was replicated in an additional 3,939 individuals of European ancestry from the Australian Twins Study and Multi-Ethnic Study of Atherosclerosis (rs2194025, P-value= 2.11 x 10(-12) in combined meta-analysis of discovery and replication cohorts). In independent studies of modest sample sizes, no significant association was found between this variant and clinical outcomes including coronary artery disease, stroke, myoca

OBJECTIVE - To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes. RESEARCH DESIGN AND METHODS - A pooled analysis using individual participant data from population-based studies around the world was performed. A systematic literature review was conducted to identify all population-based studies in general populations or individuals with diabetes who had ascertained DR from retinal photographs. Studies provided data for DR end points, including any DR, proliferative DR, diabetic macular edema, and VTDR, and also major systemic risk factors. Pooled prevalence estimates were directly age-standardized to the 2010 World Diabetes Population aged 20-79 years. RESULTS - A total of 35 studies (1980-2008) provided data from 22,896 individuals with diabetes. The overall prevalence was 34.6% (95% CI 34.5-34.8) for any DR, 6.96% (6.87-7.04) for proliferative DR, 6.81% (6.74-6.89) for diabetic macular edema, and 10.2% (10.1-10.3) for VTDR. All DR prevalence end points increased with diabetes duration, hemoglobin A1c, and blood pressure levels and were higher in people with type 1 compared with type 2 diabetes. CONCLUSIONS - There are approximately 93 million people with DR, 17 million with proliferative DR, 21million with diabeticmacular edema, and 28million with VTDR worldwide. Longer diabetes duration and poorer glycemic and blood pressure control are strongly associated with DR. These data highlight the substantial worldwide public health burden of DR and the importance of modifiable risk factors in its occurrence. This study is limited by data pooled from studies at different time points, with different methodologies and population characteristics.

Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest P value 3.87 × 10 -12 for SNP rs634990 in Caucasians, and 9.65 × 10 -4 for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 × 10 -23 for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95 % CI 1.64, 2.16, P < 0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and OR 1.33 (95 % CI 1.19, 1.49, P < 0.001) for heterozygous carriers. SNPs at locus 15q25 did not replicate significantly (P value 5.81 × 10 -2 for top SNP rs939661). We conclude that common variants at chromosome 15q14 influence susceptibility for myopia in Caucasian and Asian populations world-wide.

To investigate the relation between retinopathy and the risk of dementia. We investigated the associations between retinopathy and dementia and its subtypes Alzheimer disease (AD) and vascular dementia both cross-sectionally and prospectively in the Rotterdam Study, a large population-based cohort study. Digitized retinal images were available for 195 participants with prevalent dementia and 6,078 participants without dementia at baseline (1990-1993). Participants were reexamined in 1993-1994, 1997-1999, and 2002-2004 and were continuously monitored for development of dementia until January 1, 2007. Retinopathy was graded on fundus photographs and was defined as the presence of one or more dot/blot hemorrhages, microaneurysms, cotton wool spots, or evidence of laser treatment for retinopathy. Retinopathy was associated with prevalent dementia (age and sex-adjusted odds ratio 2.04, 95% confidence interval [CI] 1.34-3.09). Results were similar for AD and vascular dementia. During a mean follow-up of 11.4 years, 735 participants developed incident dementia, of whom 583 had AD and 80 had vascular dementia. There was no association of retinopathy at baseline with the risk of incident dementia during follow-up (age- and sex-adjusted hazard ratio 1.15, 95% CI 0.88-1.48) or the risk of incident AD or vascular dementia. Retinopathy is more prevalent in persons with dementia but is not associated with an increased risk of dementia over time. AD: Alzheimer disease ARIC: Atherosclerosis Risk in Communities CI: confidence interval CRP: C-reactive protein DSM-III-TR: Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised GMS: Geriatric Mental State schedule MMSE: Mini-Mental State Examination OR: odds ratio.

OBJECTIVE - To examine the association between early retinal arteriolar abnormalities and diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS - Data from 608 people (aged 40-80 years) with diabetes from the population-based Singapore Malay Eye Study were analyzed. Participants underwent binocular two-field digital retinal photography and quantitative sensory testing. DPN was defined as an abnormal response to a monofilament or neurothesiometer test. Quantitative changes of retinal vascular caliber and arteriolar bifurcation geometry were measured using a computer-based program. Qualitative retinal signs of retinopathy and retinal arteriolar wall signs were graded by standardized methods. RESULTS - DPN was present in 155 people (25.5%). After adjusting for age, sex, diabetes duration, HbA1c, cardiovascular risk factors, antihypertensive medication use, and peripheral arterial disease, people with suboptimal arteriolar caliber (odds ratio 1.94 [95% CI 1.22-3.10]), larger arteriolar branching coefficient (1.58 [1.03-2.42]), diabetic retinopathy (1.82 [1.20-2.75]), and focal arteriolar narrowing (2.92 [1.48-5.76]) were more likely to have DPN. Participants with a greater number of retinal microvascular signs were more likely to have DPN than those without retinal changes (6.11 [2.11-17.71] for two or more signs and 3.47 [1.18-10.21] for one sign compared with none). CONCLUSIONS - Individuals with diabetes with early retinal arteriolar abnormalities are more likely to have DPN, independent of hyperglycemia and major vascular risk factors. These data support the hypothesis that early microvascular dysfunction, evident in the retina, is an independent risk factor for DPN.

Alzheimer's disease (AD) is the most common cause of dementia. Furthermore, over the last few decades, there has been a shift towards identifying earlier stages of AD, which include mild cognitive impairment (MCI). Improved methods of screening and early detection are essential to identify cognitively normal individuals who have a high risk of developing MCI and AD, so that interventions can be developed to delay the progression of specific disease-related pathologies. Thus far, novel biomarkers that have been examined include structural and functional neuroimaging as well as biochemical analysis of cerebrospinal fluid. However, in spite of these efforts, there is still an urgent need for unravelling additional novel biomarkers for AD and MCI. As the retina shares many features with the brain, including embryological origin, anatomical (such as microvascular bed) and physiological characteristics (such as blood-tissue barrier), it has been suggested that the retina may provide an easily accessible and non-invasive way of examining pathology in the brain. While most AD-related pathology occurs in the brain, the disease has also been reported to affect different regions of the retina, including the macular region and optic disc. Studies have suggested that retinal pathology, such as deposits in the macular region, decreased retinal nerve fibre thickness, and optic disc cupping and retinal microvascular abnormalities may be related to AD and cognitive impairment. This article presents a review of current literature on retinal involvement in AD and MCI.

Background: Health of migrants is a major public health challenge faced by governments and policy makers. Asian Indians are among the fastest growing migration groups across Asia and the world, but the impact of migration and acculturation on diabetes and diabetes-related eye complications among Indians living in urban Asia remains unclear. Methodologies/Principal Findings: We evaluated the influence of migration and acculturation (i.e., migration status and length of residence) on the prevalence of type-2 diabetes mellitus (T2DM) and diabetes-related eye complications (diabetic retinopathy (DR) and cataract), among first-generation (defined as participant born in India with both parents born in India, n = 781) and second-generation (participants born in Singapore with both parents born in India, n = 1,112) Indian immigrants from a population-based study of Adult Indians in Singapore. Diabetes was defined as HbA1c≥6.5%, use of diabetic medication or a physician diagnosis of diabetes. Retinal and lens photographs were graded for the presence of DR and cataract. Compared to first generation immigrants, second generation immigrants had a higher age- and gender-standardized prevalence of T2DM (34.4% versus 29.0%, p<0.001), and, in those with T2DM, higher age- and gender-standardized prevalence of DR (31.7% versus 24.8%, p<0.001), nuclear cataract (13.6% versus 11.6%, p<0.001), and posterior sub-capsular cataract (6.4% versus 4.6%, p<0.001). Among first generation migrants, longer length of residence was associated with significantly younger age of diagnosis of diabetes and greater likelihood of having T2DM and diabetes-related eye complications. Conclusion: Second generation immigrant Indians and longer length of residence are associated with higher prevalence of diabetes and diabetes-related complications (i.e., DR and cataract) among migrant Indians living in Singapore. These data highlight potential worldwide impacts of migration patterns on the risk and burden of di

Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a geno

Background: Retinal vessels provide a unique opportunity to study both systemic and cerebrovascular disease. Smaller retinal arteriolar calibers are strongly related to hypertension, whereas larger retinal venular calibers are more related to inflammation, cerebral hypoperfusion, and cerebrovascular disease. Whether retinal vessel calibers are related to dementia remains unclear. Methods: We investigated whether retinal arteriolar and venular calibers are associated with risk of dementia, and its subtypes Alzheimer disease (AD) and vascular dementia, in the prospective population-based Rotterdam Study. Digitized retinal images were available in 5,553 participants aged 55 years or over and dementia-free at baseline (1990-1993). Participants were re-examined in 1993-1994, 1997-1999, and 2002-2004 and were continuously monitored for development of dementia. Results: During a mean follow-up of 11.6 years, 655 participants developed dementia. AD was diagnosed in 519 and vascular dementia in 73 participants. Larger venular calibers were associated with an increased risk of dementia, in particular vascular dementia (age- and sex-adjusted hazard ratio per SD increase: 1.31; 95% confidence interval 1.06-1.64), but not AD. The association remained significant after adjustment for stroke and cardiovascular risk factors. Smaller arteriolar calibers were also associated with an increased risk of vascular dementia, yet only when adjusted for venular calibers. Conclusions: Retinal venular widening is associated with an increased risk of vascular dementia. Our findings are in line with previous observations in stroke and cerebral small-vessel disease and suggest that the association between larger retinal venular calibers and dementia may reflect cerebral hypoperfusion and subsequent ischemia. Copyright

Corneal astigmatism refers to refractive abnormalities and irregularities in the curvature of the cornea, and this interferes with light being accurately focused at a single point in the eye. This ametropic condition is highly prevalent, influences visual acuity, and is a highly heritable trait. There is currently a paucity of research in the genetic etiology of corneal astigmatism. Here we report the results from five genome-wide association studies of corneal astigmatism across three Asian populations, with an initial discovery set of 4,254 Chinese and Malay individuals consisting of 2,249 cases and 2,005 controls. Replication was obtained from three surveys comprising of 2,139 Indians, an additional 929 Chinese children, and an independent 397 Chinese family trios. Variants in PDGFRA on chromosome 4q12 (lead SNP: rs7677751, allelic odds ratio = 1.26 (95% CI: 1.16-1.36), Pmeta= 7.87×10-9) were identified to be significantly associated with corneal astigmatism, exhibiting consistent effect sizes across all five cohorts. This highlights the potential role of variants in PDGFRA in the genetic etiology of corneal astigmatism across diverse Asian populations.

Refractive errors are the most common ocular disorders worldwide and may lead to blindness. Although this trait is highly heritable, identification of susceptibility genes has been challenging. We conducted a genome-wide association study for refractive error in 5,328 individuals from a Dutch population-based study with replication in four independent cohorts (combined 10,280 individuals in the replication stage). We identified a significant association at chromosome 15q14 (rs634990, P = 2.21 × 10−14). The odds ratio of myopia compared to hyperopia for the minor allele (minor allele frequency = 0.47) was 1.41 (95% CI 1.16–1.70) for individuals heterozygous for the allele and 1.83 (95% CI 1.42–2.36) for individuals homozygous for the allele. The associated locus is near two genes that are expressed in the retina, GJD2 and ACTC1, and appears to harbor regulatory elements which may influence transcription of these genes. Our data suggest that common variants at 15q14 influence susceptibility for refractive errors in the general population.

There is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. We analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and replicated findings in four independent Caucasian cohorts (n = 6,652). All participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. In the discovery cohorts, 179 single nucleotide polymorphisms (SNP) spread across five loci were significantly associated (p<5.0×10-8) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0%-3.2% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p = 1.61×10-25, within the RASIP1 locus), rs225717 (6q24; p = 1.25×10-16, adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p = 2.15×10-13, in the region of ATXN2,SH2B3 and PTPN11 loci), and rs17421627 (5q14; p = 7.32×10-16, adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.

The optic nerve head is involved in many ophthalmic disorders, including common diseases such as myopia and open-angle glaucoma. Two of the most important parameters are the size of the optic disc area and the vertical cup-disc ratio (VCDR). Both are highly heritable but genetically largely undetermined. We performed a meta-analysis of genome-wide association (GWA) data to identify genetic variants associated with optic disc area and VCDR. The gene discovery included 7,360 unrelated individuals from the population-based Rotterdam Study I and Rotterdam Study II cohorts. These cohorts revealed two genome-wide significant loci for optic disc area, rs1192415 on chromosome 1p22 (p =6.72*10-19) within 117 kb of the CDC7 gene and rs1900004 on chromosome 10q21.3-q22.1 (p=2.67*10-33) within 10 kb of the ATOH7 gene. They revealed two genome-wide significant loci for VCDR, rs1063192 on chromosome 9p21 (p =6.15*10-11) in the CDKN2B gene and rs10483727 on chromosome 14q22.3-q23 (p=2.93*10-10) within 40 kbp of the SIX1 gene. Findings were replicated in two independent Dutch cohorts (Rotterdam Study III and Erasmus Rucphen Family study; N=3,612), and the TwinsUK cohort (N=843). Meta-analysis with the replication cohorts confirmed the four loci and revealed a third locus at 16q12.1 associated with optic disc area, and four other loci at 11q13, 13q13, 17q23 (borderline significant), and 22q12.1 for VCDR. ATOH7 was also associated with VCDR independent of optic disc area. Three of the loci were marginally associated with open-angle glaucoma. The protein pathways in which the loci of optic disc area are involved overlap with those identified for VCDR, suggesting a common genetic origin. © 2010 Ramdas et al.

The association between a smaller retinal arteriolar-to-venular ratio (AVR) and incident diabetes may be due to arteriolar narrowing, venular dilatation, or both. We investigated associations between baseline vessel diameters and incident impaired fasting glucose or diabetes in a population-based cohort (aged > or =55 years). Baseline retinal vessel diameters (1990-1993) were measured on digitized images of 2,309 subjects with a normal glucose tolerance test (postload glucose <7.8 mmol/l). At follow-up (1997-1999), impaired fasting glucose was defined as 6.1-7.0 mmol/l and diabetes as > or =7.0 mmol/l and/or antidiabetic medication use. Odds ratios (ORs) per SD increase in venular diameters were 1.13 (95% CI 1.00-1.29) for impaired fasting glucose and 1.09 (0.90-1.33) for diabetes. ORs per SD decrease in arteriolar diameters were 1.12 (0.98-1.27) and 1.08 (0.89-1.31) and per SD decrease in AVR were 1.29 (1.13-1.46) and 1.19 (0.98-1.45). After adjustment for cardiovascular risk factors, the associations were unaltered for venules and disappeared for arterioles. After stratification on age, associations between venular dilatation and impaired fasting glucose (1.23 [1.02-1.47]) or diabetes (1.18 [0.89-1.56]) were mainly present in participants aged <70 years. In conclusion, in our study, the risk of impaired fasting glucose and diabetes with AVR was explained by venular dilatation rather than arteriolar narrowing, warranting more focus on the causes of this dilatation.

The role of IGF-I in the pathogenesis of diabetic retinopathy is unclear. We studied, prospectively, the relationship between an IGF-I gene polymorphism, retinal vessel diameters, and incident diabetic retinopathy in subjects with impaired glucose tolerance (IGT) or type 2 diabetes. In all 5,505 participants of the population-based Rotterdam Study (775 with IGT, 394 with type 2 diabetes, and 4,336 control subjects), fundus color transparencies were taken at baseline (between 1990 and 1993) and at follow-up (from 1997 to 1999). The wild-type genotype (i.e., carriers of the 192- or 194-bp alleles) was present in 72.7% of the participants, while 27.3% were variant carriers. Variant carriers with IGT or type 2 diabetes appeared to have larger retinal arteriolar and venular diameters at baseline than individuals with the wild-type genotype, but these differences did not reach statistical significance. This trend was especially observed in subjects who developed retinopathy at follow-up. In variant carriers with IGT/diabetes, an increase (odds ratio 1.8 [95% CI 1.0-3.2]; P = 0.04) in the risk of retinopathy was observed compared with participants with the wild-type genotype. In conclusion, our findings suggest that this IGF-I gene polymorphism is associated with an increased risk of diabetic retinopathy.

PURPOSE: To determine whether blood pressure and subclinical atherosclerosis are associated with incident age-related maculopathy (ARM). METHODS: The study was performed within the Rotterdam Study, a population-based, prospective cohort study in Rotterdam, The Netherlands. A total of 4822 subjects who at baseline were aged 55 years more, were free of ARM, and participated in at least one of two follow-up examinations after a mean of 2 and 6.5 years, were included in the study. At baseline, blood pressure and the presence of atherosclerosis were determined. ARM was assessed according to the International Classification and Grading System and defined as large, soft drusen with pigmentary changes; indistinct drusen; or atrophic or neovascular age-related macular degeneration. RESULTS: After a mean follow-up of 5.2 years, incident ARM was diagnosed in 417 subjects. Increased systolic blood pressure or pulse pressure was associated with a higher risk of ARM. Adjusted for age, gender, smoking, total and high-density lipoprotein cholesterol, body mass index, and diabetes mellitus, odds ratios (OR) per 10-mm Hg increase were 1.08 (95% confidence interval [CI]: 1.03-1.14) and 1.11 (95% CI: 1.04-1.18), respectively. Moreover, different measures of atherosclerosis were associated with the risk of ARM. An increase in carotid wall thickness (OR per 1 SD, 1.15; 95% CI: 1.03-1.28) increased the risk of ARM. The lowest compared with the highest tertile of ankle-arm index had an OR of 1.32 (95% CI: 1.00-1.75). A weak association was found between aortic calcifications and the risk of ARM. CONCLUSIONS: Elevated systolic blood or pulse pressure or the presence of atherosclerosis may increase the risk of development of ARM.

PURPOSE: To study the relationship between baseline spherical equivalents (SphE) of refraction and prevalent as well as incident age-related maculopathy (pARM and iARM, respectively). METHODS: The study was performed as part of the Rotterdam Study, a population-based, prospective cohort study. The SphE (in diopters), measured with autorefraction and subjective optimization, was recorded in 6209 subjects aged 55 years or more. Aphakic or pseudophakic eyes at baseline were excluded. Stereoscopic transparencies of the macular region were graded according to the International Classification and Grading System. ARM was defined as large soft drusen with pigmentary changes, or indistinct drusen, or atrophic or neovascular age-related macular degeneration (AMD). For the prevalence analyses, ARM was classified into no, p(early)ARM, or pAMD, and in each subject the eye with the most advanced ARM and the corresponding refraction was selected. After a mean 5.2 years of follow-up, 4935 subjects had complete data for these incidence analyses. In each subject, the eye with iARM was selected. RESULTS: The age- and gender-adjusted odds ratio (OR) of pARM (n = 536) for every diopter of progress toward hyperopia was 1.09 (95% confidence interval [CI]1.04-1.13). For p(early)ARM (n = 440) the OR was 1.09 (1.04-1.14) and for pAMD (n = 96) the OR was 1.09 (1.00-1.19). Baseline refraction was significantly associated with increased risk of iARM (n = 497). For each diopter of progress toward hyperopia the OR was 1.05 (95% CI 1.01-1.10). Additional adjustments for smoking, atherosclerosis, and blood pressure did not alter the relationship. CONCLUSIONS: These population-based incidence data confirm results from prevalence and case-control studies that there is an association between hyperopia and ARM.