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.
Population-based, cross-sectional European Eye Study in 7 countries in Europe.
Four thousand seven hundred fifty participants, 65 years of age and older, recruited through random sampling.
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.
Odds ratios (ORs) for stage of AMD associated with genetic variations in ARMS2 and CFH and interactions between ARMS2 and smoking status.
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).
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.
Retinal vessel diameters, in particular larger venular diameters, have been associated with cerebrovascular disease. Larger retinal venular diameters may reflect cerebral ischemia. The authors ...investigated whether arteriolar oxygen saturation (SaO2) and total cerebral blood flow (CBF), indicators of cerebral oxygen supply, are associated with retinal arteriolar or venular diameters.
Cross-sectional study performed within the population-based Rotterdam Study.
Randomly selected participants aged 55 years or older (n = 696), who underwent both an eye examination and brain magnetic resonance imaging (MRI).
Arteriolar oxygen saturation was determined by pulse oximetry on the right index finger. Cerebral blood flow was assessed using a phase-contrast MRI sequence that measured the flow in the basilar and both internal carotid arteries. Brain volume was measured to express CBF per 100 ml brain volume. Retinal arteriolar and venular diameters were measured on digitized fundus color transparencies on 1 eye of each participant. Regression models were used to investigate the association of SaO(2) and CBF with retinal vessel diameters.
Mean retinal arteriolar and venular diameters (in micrometers).
Lower SaO2 was associated with larger venular diameters. Persons with SaO(2) less than 96% (n = 113) had on average 5 microm larger venular diameters compared with those with SaO(2) of 96% or more (n = 583; age- and gender-adjusted mean difference, 5.6 microm; 95% confidence interval, 1.2-10.0). Cerebral blood flow was not related to venular diameters when analyzed separately. Additional analyses showed that the association between SaO(2) and venular widening was confined to participants within the lowest tertile of CBF. No associations were found between SaO(2) or CBF and arteriolar diameters. Additional adjustment for established cardiovascular risk factors did not change the results.
An association of lower SaO(2) with larger retinal venular diameters was observed, in particular in the presence of lower CBF. These findings suggest that venular widening may reflect a lower oxygen supply, especially to the brain.
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.
Meta-analysis of prevalence data.
A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe.
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).
Prevalence of early and late AMD, BCVA, and number of AMD cases.
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.
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.
To determine the association between the ocular perfusion pressure (OPP; essentially the difference between the blood pressure and the intraocular pressure IOP) and incident open-angle glaucoma ...(OAG).
A subset of 3882 participants of the population-based Rotterdam Study for whom data from ophthalmic examinations at baseline and follow-up and blood pressure measurements at baseline were available, and who did not have OAG at baseline, were included. Associations between the mean, systolic and diastolic OPP, and incident OAG were assessed using Cox regression models adjusted for age and sex, with and without adjustment for IOP.
During a mean follow-up of 9.8 years, 103 participants (2.7%) developed OAG. The association between the mean OPP and incident OAG was not significant (hazard ratio 0.995 per mm Hg increase in mean OPP; 95% confidence interval 0.971-1.019) when adjusted for IOP, but became significant if not adjusted for IOP (0.968; 0.945-0.992). The systolic and diastolic OPP showed a pattern similar to that of the mean OPP, though less significant.
The OPP appears to be associated with incident OAG but this association seems to be due to the fact that the IOP, a strong risk factor for OAG, is part of the OPP, rather than that OPP is an independent OAG risk factor itself.
Human iris color was one of the first traits for which Mendelian segregation was established. To date, the genetics of iris color is still not fully understood and is of interest, particularly in ...view of forensic applications. In three independent genome-wide association (GWA) studies of a total of 1406 persons and a genome-wide linkage study of 1292 relatives, all from the Netherlands, we found that the 15q13.1 region is the predominant region involved in human iris color. There were no other regions showing consistent genome-wide evidence for association and linkage to iris color. Single nucleotide polymorphisms (SNPs) in the
HERC2 gene and, to a lesser extent, in the neighboring
OCA2 gene were independently associated to iris color variation.
OCA2 has been implicated in iris color previously. A replication study within two populations confirmed that the
HERC2 gene is a new and significant determinant of human iris color variation, in addition to
OCA2. Furthermore,
HERC2 rs916977 showed a clinal allele distribution across 23 European populations, which was significantly correlated to iris color variation. We suggest that genetic variants regulating expression of the
OCA2 gene exist in the
HERC2 gene or, alternatively, within the 11.7 kb of sequence between
OCA2 and
HERC2, and that most iris color variation in Europeans is explained by those two genes. Testing markers in the
HERC2-OCA2 region may be useful in forensic applications to predict eye color phenotypes of unknown persons of European genetic origin.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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.
Age-related macular degeneration (AMD) and stroke are both frequent diseases in the elderly. A link between AMD and stroke has been suggested, because both disorders have many risk factors in common. ...The aim of this study was to investigate the association between AMD and stroke and the subtypes cerebral infarction and intracerebral hemorrhage in the general elderly population.
This study was part of the population-based Rotterdam Study and included 6207 participants aged ≥ 55 years who were stroke-free at baseline (1990 to 1993). Signs of AMD were assessed on fundus photographs at baseline and at regular follow-up examinations and were categorized in 5 stages (0 to 4) representing an increasing severity. Late AMD (Stage 4) was subdivided into dry and wet AMD. Follow-up for incident stroke was complete up to January 1, 2007. Data were analyzed using time-dependent Cox regression models adjusted for age, sex, and potential confounders.
During a median follow-up of 13.6 years, 726 participants developed a stroke (397 cerebral infarction, 59 intracerebral hemorrhage, 270 unspecified). Late AMD was associated with an increased risk of any stroke (hazard ratio, 1.56; 95% CI, 1.08 to 2.26) due to a strong association with intracerebral hemorrhage (hazard ratio, 6.11; 95% CI, 2.34 to 15.98). In contrast, late AMD was not associated with cerebral infarction. Earlier AMD stages were not associated with risk of stroke or any of its subtypes.
We found that late AMD is strongly associated with intracerebral hemorrhage, but not with cerebral infarction, in the general elderly population.
From where does “rete” in retina originate? de Jong, Paulus T. V. M.
Graefe's archive for clinical and experimental ophthalmology,
10/2014, Volume:
252, Issue:
10
Journal Article
Peer reviewed
Open access
Full text
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aspirin Use and Aging Macula Disorder de Jong, Paulus T. V. M; Wang, Jie Jin; Fletcher, Astrid E
JAMA ophthalmology,
01/2014, Volume:
132, Issue:
1
Journal Article
Epidemiology of Age-Related Maculopathy: A Review van Leeuwen, Redmer; Caroline C. W. Klaver; Vingerling, Johannes R. ...
European journal of epidemiology,
2003, Volume:
18, Issue:
9
Journal Article
Peer reviewed
Age-related maculopathy (ARM) is a degenerative disease of the retina and the leading cause of incurable blindness and visual impairment in industrialized countries. By definition, ARM is confined to ...the age-category above 50 years. The aetiology of ARM is still unknown, despite intensive research on many fronts. In this paper, we provide a review of the epidemiology of ARM. The most prominent findings were an exponential increase in frequency with age, a significant familial and genetic component, and a strong association with smoking. Other risk factors that were found less consistently were atherosclerosis, low intake of antioxidant nutrients, and cataract extraction. Future studies, both observational and experimental, will hopefully identify more risk factors that are amenable to prevention.
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