Background:The excess risk of bilateral visual impairment (BVI; bilateral visual acuity <0.5) among individuals with amblyopia is an argument for screening for amblyopia, but data are ...scarce.Methods:The risk was estimated by determining the incidence of BVI in the Rotterdam Study, a population-based cohort of subjects aged 55 years or over (n = 5220), including 192 individuals with amblyopia (3.7%). Using a multistate lifetable, the lifetime risk and excess period spent with BVI were determined.Results:The relative risk of BVI for amblyopes was 2.6 (95% confidence interval 1.4–4.5). For individuals with amblyopia, the lifetime risk of BVI was 18%, whereas they lived on average 7.2 years with BVI. For non-amblyopic individuals, these figures were 10% and 6.7 years, respectively.Conclusion:Amblyopia nearly doubles the lifetime risk of BVI and affected individuals spent an extra six months with BVI. This study provides data for future cost-effectiveness analyses.
Retinal vessels may provide a way to study the cerebral microcirculation. In particular, larger retinal venular diameters have been associated with cerebrovascular disease. An inflammatory response ...may underlie this association. In a population‐based cohort study among 5,279 participants aged 55 years or older with graded retinal vessel diameters, we observed that greater serum levels of C‐reactive protein and fibrinogen and greater lipoprotein‐associated phospholipase A2 activity were strongly associated with larger venular diameters. Weaker associations were found with arteriolar diameters. Our findings support the hypothesis that larger retinal venular diameters reflect systemic inflammation and suggest that inflammation is involved in cerebrovascular disease. Ann Neurol 2007
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
OBJECTIVE—N-terminal pro-B–type natriuretic peptide (NT-proBNP) is a marker of cardiac dysfunction and has been linked to various indices of large vessel disease. However, it remains unclear whether ...NT-proBNP also relates to microvascular damage. In a community-dwelling population, we studied the association between NT-proBNP and retinal microvascular damage.
APPROACH AND RESULTS—From the population-based Rotterdam Study, we included 8437 participants (mean age 64.1 years and 59% women) without a history of cardiovascular disease, with NT-proBNP data and gradable retinal images. NT-proBNP serum levels were measured using an immunoassay. Retinopathy signs, that is, exudates, microaneurysms, cotton wool spots, and dot/blot hemorrhages, present on fundus photographs were graded in the total study population; retinal vascular calibers, that is, arteriolar and venular calibers, were semiautomatically measured in a subsample (n=2763) of the study population. We conducted cross-sectional analyses on the association between NT-proBNP and retinal microvascular damage using logistic and linear regression models, adjusting for age, sex, and cardiovascular risk factors. We found that NT-proBNP was associated with the presence of retinopathy (adjusted odds ratio 95% confidence interval per SD increase in natural log-transformed NT-proBNP1.14 1.03–1.27). We also found that higher NT-proBNP was associated with narrower arteriolar calibers (adjusted mean difference in arteriolar caliber per SD increase in natural log-transformed NT-proBNP−0.89 µm −1.54 to −0.24). This association remained unchanged after excluding participants with retinopathy signs.
CONCLUSIONS—In participants free of clinical cardiovascular disease, higher levels of NT-proBNP are associated with retinal microvascular damage, suggesting a potential role for NT-proBNP as marker for small vessel disease.
Reticular pseudodrusen (RPD) are considered to be a distinct feature in AMD. Population studies have studied the epidemiology of RPD using standard color fundus photographs (CFP). However, recent ...studies have shown that RPD are better imaged using near-infrared (NIR) imaging. We studied the epidemiology of RPD in a large population-based study using NIR and CFP.
Participants aged 65+ years from the Rotterdam Study underwent ophthalmologic examination including NIR and CFP. Both images were graded for the presence of RPD and soft indistinct drusen (SID). Associations with demographic and environmental factors, 26 genetic variants, and total genetic risk score were analyzed using logistic regression analysis.
Reticular pseudodrusen were detected in 137 (4.9%) of 2774 study participants; of these, 92.7% were detected with NIR imaging and 38% on CFP. Most eyes with RPD showed presence of SID, whereas other drusen types coincided less frequently. Reticular pseudodrusen were significantly associated with age (odds ratio OR 1.21, 95% Confidence Interval CI 1.17-1.24) and female sex (OR 2.10, 95% CI 1.41-3.13). Environmental factors did not show a significant association with RPD. Major AMD risk variants were significantly associated with RPD and SID; however, ARMS2, C3, and VEGFA were more associated with RPD (RPD vs. SID P < 0.05). Total genetic risk score did not differ significantly (P = 0.88).
Detection of RPD was better with NIR imaging than on CFP in a population-based setting. Presence of RPD often coincided with presence of SID; however, they showed quantitative differences in genetic risk profile.
To study associations between aspirin use and early and late aging macula disorder (AMD).
Population-based cross-sectional European Eye Study in 7 centers from northern to southern Europe.
In total, ...4691 participants 65 years of age and older, collected by random sampling.
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.
Odds ratios (ORs) for AMD in aspirin users.
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).
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.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
To examine risk factors for incident age-related macular degeneration (AMD) after combining data from 3 population-based cohort studies.
Population-based cohort study.
A population of 9523 adults ...(age range, 43–95 years at baseline) living in Australia, The Netherlands, and the United States who participated in a baseline examination and a follow-up examination on average 5 or 6 years later.
Similar procedures were used at all study sites. Examinations included a standardized questionnaire, pupillary dilation, and stereoscopic color fundus photography. Fundus photographs were graded for lesions associated with AMD using the Wisconsin and International Age-Related Maculopathy Grading Systems. Senior investigators from each site adjudicated all photos graded as late AMD.
Incidence of late AMD.
Among studies, distributions for most risk factors differed, and overall incidence rates were similar. In the Beaver Dam Eye Study, total serum cholesterol was inversely associated with incident neovascular AMD. In the Blue Mountains Eye Study, current smoking (defined as smoking at the time of the baseline examination) was associated with an increased risk of incident geographic atrophy and late AMD; increased total serum cholesterol, having diabetes, and older age at menopause were positively associated with incident geographic atrophy; and an increase in high-density lipoprotein serum cholesterol was inversely related to incident geographic atrophy. In the Rotterdam Study, current smoking was associated with an increased risk of incident geographic atrophy, neovascular AMD, and late AMD; past smoking was associated with an increased risk of incident neovascular AMD and late AMD; and an increased number of years between menarche and menopause was directly related to incident geographic atrophy. After pooling data, the only statistically significant relationships found were between smoking and total serum cholesterol and incident AMD. Current smoking was associated with an increased incidence of geographic atrophy and late AMD (odds ratios ORs relative to nonsmokers: 2.83 and 2.35, respectively; ORs relative to past smokers: 2.80 and 1.82, respectively), and total serum cholesterol was associated directly with incident geographic atrophy (OR: 1.08 per 10 mg/dl) and inversely with incident neovascular AMD (OR: 0.94 per 10 mg/dl).
Pooled data support a growing body of evidence indicating that smoking is related to an increased risk of incident AMD. Current smokers were at higher risk of incident AMD than both past smokers and those who never smoked. The relationships found in this study between total serum cholesterol and incident geographic atrophy and neovascular AMD are not readily explained.
Although ocular tissues involved in aging macula disorder (AMD) were already known in 300 BC, the last type of photoreceptors was discovered only 10 years ago. The earliest descriptions of AMD ...appeared around 1850. It took over 150 years, till a clearer concept of AMD was formulated and even longer to grasp its pathophysiology. The uncertainty of researchers about the pathogenesis of AMD over the last century is reflected in its changing terminology. The evolution of this terminology is provided in a table to afford the reader a better insight into explanations proposed by researchers during this quest.
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.
Population-based, cross-sectional study in a random sample aged 65 years or older from 7 European countries.
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.
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.
Adjusted odds ratio (OR) for 3 outcomes (early AMD, late AMD, nvAMD).
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.
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.
To investigate whether diabetes mellitus is a risk factor for open-angle glaucoma (OAG).
Prospective population-based cohort study.
Participants ages > or =55 years from the Rotterdam Study, The ...Netherlands.
Participants at risk for incident OAG (iOAG) underwent at baseline (1990-1993) and follow-up (1997-1999) the same ophthalmic examination including intraocular pressure (IOP) measurement, visual field testing, and simultaneous stereo optic disc photography. At baseline, diabetes mellitus was defined as the use of antidiabetic medication and/or a random or postload glucose value > or =11.1 mmol/l. The diagnosis of OAG was made with an algorithm based on optic disc measures and visual fields, independent of the IOP.
Incident OAG.
In total, 3837 participants without OAG at baseline were reexamined. After a mean follow-up time of 6.5 years, iOAG developed in 87 persons. The relative risk of iOAG associated with baseline diabetes was 0.82 (0.33-2.05). After adjustment for age, gender, follow-up time, IOP, IOP-lowering treatment, body mass index, and systemic hypertension, the relative risk of iOAG was 0.65 (0.25-1.64).
In this prospective population-based study, diabetes mellitus was not a risk factor for OAG.
To explore the association between polymorphisms in the complement component 3 (C3) gene and age-related macular degeneration (AMD), and to investigate the modifying effect of complement factor H ...(CFH) Y402H, LOC387715 A69S and smoking.
Pooled data from the prospective, population-based Rotterdam Study (enrolment between 1990 and 1993, and 3 follow-up examinations between September 1, 1993, and December 31, 2004) and an independent case-control study from the Netherlands.
The Rotterdam Study comprised a total of 6418 persons aged >or=55 years who had gradable fundus photographs. The case-control study consisted of 357 unrelated AMD patients and 173 control individuals aged >or=55 years.
The variants R102G and P314L of the C3 gene, CFH Y402H and LOC387715 A69S, were genotyped in all study participants. Information on cigarette smoking was obtained by interview at baseline.
Early and late stages of prevalent and incident AMD, graded according to the international classification and grading system for AMD.
We found a population frequency of 0.217 for R102G and 0.211 for P314L in the Rotterdam Study. Both alleles significantly increased the risk of early AMD and all subtypes of late AMD, and this risk seemed to be independent of CFH Y402H, LOC387715 A69S, and smoking. Detailed analysis showed that the haplotype carrying both alleles had the highest frequency difference between cases and controls (P=0.006). We estimated a total population-attributable risk of 14.6%. A meta-analysis of all currently available data yielded a pooled odds ratio (OR) of 1.61 (95% confidence interval CI, 1.46-1.78) for the R102G allele, and an OR of 1.50 (95% CI, 1.31-1.71) for the P314L allele.
Our study showed a significant association between variants in the C3 gene and AMD and further highlights the crucial role of the complement pathway in the etiology of AMD.
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