There is an urgency to find new treatment strategies that could prevent or delay the onset or progression of AMD. Different classes of lipids and lipoproteins metabolism genes have been associated ...with AMD in a multiple ways, but despite the ever-increasing knowledge base, we still do not understand fully how circulating lipids or local lipid metabolism contribute to AMD. It is essential to clarify whether dietary lipids, systemic or local lipoprotein metabolismtrafficking of lipids in the retina should be targeted in the disease. In this article, we critically evaluate what has been reported in the literature and identify new directions needed to bring about a significant advance in our understanding of the role for lipids in AMD. This may help to develop potential new treatment strategies through targeting the lipid homeostasis.
•High dietary intake of omega-3 is consistently associated with decreased risk of AMD.•HDL-C levels are elevated and triglycerides are decreased in AMD patients.•Composition and activity of HDL particles might be relevant for AMD.•Genes involved in cholesterol transport associate with both AMD and lipid levels.•AMD pathogenesis may be related to circulating lipids, local lipid transport, or both.
Abstract Biomarkers can help unravel mechanisms of disease and identify new targets for therapy. They can also be useful in clinical practice for monitoring disease progression, evaluation of ...treatment efficacy and risk assessment in multifactorial diseases, such as age-related macular degeneration (AMD). AMD is a highly prevalent progressive retinal disorder for which multiple genetic and environmental risk factors have been described, but the exact etiology is not yet fully understood. Many compounds have been evaluated for their association with AMD. We performed an extensive literature review of all compounds measured in serum, plasma, vitreous, aqueous humor and urine of AMD patients. Over 3600 articles were screened resulting in more than 100 different compounds analyzed in AMD studies, involved in neovascularization, immunity, lipid metabolism, extracellular matrix, oxidative stress, diet, hormones, and comorbidities (such as kidney disease). For each compound we provide a short description of its function and discuss the results of the studies in relation to its usefulness as AMD biomarker. Additionally, biomarkers identified by hypothesis-free techniques, including metabolomics, proteomics and epigenomics, are covered. In summary, compounds belonging to the oxidative stress pathway, the complement system, and lipid metabolism are the most promising biomarker candidates for AMD. We hope that this comprehensive survey of the literature on systemic and ocular fluid compounds as potential biomarkers in AMD will provide a stepping stone for future research and possible implementation in clinical practice.
The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, ...psychiatric, dermatological, oncological, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in over a 1,000 research articles and reports (see www. erasmus-epidemiology. nl/rotterdamstudy).This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods.
Myopia (ie, nearsightedness) is becoming the most common eye disorder to cause blindness in younger persons in many parts of the world. Visual impairment due to myopia is associated with structural ...changes of the retina and the globe because of elongation of the eye axis. How axial length-a sum of the anterior chamber depth, lens thickness, and vitreous chamber depth-and myopia relate to the development of visual impairment over time is unknown.
To evaluate the association between axial length, spherical equivalent, and the risk of visual impairment and to make projections of visual impairment for regions with high prevalence rates.
This cross-sectional study uses population-based data from the Rotterdam Study I (1990 to 1993), II (2000 to 2002), and III (2006 to 2008) and the Erasmus Rucphen Family Study (2002 to 2005) as well as case-control data from the Myopia Study (2010 to 2012) from the Netherlands. In total, 15 404 individuals with data on spherical equivalent and 9074 individuals with data on axial length were included in the study; right eyes were used for analyses. Data were analyzed from September 2014 to May 2016.
Visual impairment and blindness (defined according to the World Health Organization criteria as a visual acuity less than 0.3) and predicted rates of visual impairment specifically for persons with myopia.
Of the 15 693 individuals included in this study, the mean (SD) age was 61.3 (11.4) years, and 8961 (57.1%) were female. Axial length ranged from 15.3 to 37.8 mm; 819 individuals had an axial length of 26 mm or greater. Spherical equivalent ranged from -25 to +14 diopters; 796 persons had high myopia (ie, a spherical equivalent of -6 diopters or less). The prevalence of visual impairment varied from 1.0% to 4.1% in the population-based studies, was 5.4% in the Myopia Study, and was 0.3% in controls. The prevalence of visual impairment rose with increasing axial length and spherical equivalent, with a cumulative incidence (SE) of visual impairment of 3.8% (1.3) for participants aged 75 years with an axial length of 24 to less than 26 mm and greater than 90% (8.1) with an axial length of 30 mm or greater. The cumulative risk (SE) of visual impairment was 5.7% (1.3) for participants aged 60 years and 39% (4.9) for those aged 75 years with a spherical equivalent of -6 diopters or less. Projections of these data suggest that visual impairment will increase 7- to 13-fold by 2055 in high-risk areas.
This study demonstrated that visual impairment is associated with axial length and spherical equivalent and may be unavoidable at the most extreme values in this population. Developing strategies to prevent the development of myopia and its complications could help to avoid an increase of visual impairment in the working-age population.
Myopia and hyperopia are at opposite ends of the continuum of refraction, the measure of the eye′s ability to focus light, which is an important cause of visual impairment (when aberrant) and is a ...highly heritable trait. We conducted a genome-wide association study for refractive error in 4,270 individuals from the TwinsUK cohort. We identified SNPs on 15q25 associated with refractive error (rs8027411, P = 7.91 × 10−8). We replicated this association in six adult cohorts of European ancestry with a combined 13,414 individuals (combined P = 2.07 × 10−9). This locus overlaps the transcription initiation site of RASGRF1, which is highly expressed in neurons and retina and has previously been implicated in retinal function and memory consolidation. Rasgrf1−/− mice show a heavier average crystalline lens (P = 0.001). The identification of a susceptibility locus for refractive error on 15q25 will be important in characterizing the molecular mechanism responsible for the most common cause of visual impairment.
The aim of the study was to investigate the relationship between serum 25(OH)D levels and axial length (AL) and myopia in 6-year-old children. A total of 2666 children aged 6 years participating in ...the birth-cohort study Generation R underwent a stepwise eye examination. First, presenting visual acuity (VA) and AL were performed. Second, automated cycloplegic refraction was measured if LogMAR VA > 0.1. Serum 25-hydroxyvitamin D 25(OH) D was determined from blood using liquid chromatography/tandem mass spectrometry. Vitamin D related SNPs were determined with a SNP array; outdoor exposure was assessed by questionnaire. The relationships between 25(OH)D and AL or myopia were investigated using linear and logistic regression analysis. Average 25(OH)D concentration was 68.8 nmol/L (SD ± 27.5; range 4-211); average AL 22.35 mm (SD ± 0.7; range 19.2-25.3); and prevalence of myopia 2.3 % (n = 62). After adjustment for covariates, 25(OH)D concentration (per 25 nmol/L) was inversely associated with AL (β -0.043; P < 0.01), and after additional adjusting for time spent outdoors (β —0.038; P < 0.01). Associations were not different between European and non-European children (β —0.037 and β —0.039 respectively). Risk of myopia (per 25 nmol/L) was OR 0.65 (95 % CI 0.46-0.92). None of the 25(OH)D related SNPs showed an association with AL or myopia. Lower 25(OH)D concentration in serum was associated with longer AL and a higher risk of myopia in these young children. This effect appeared independent of outdoor exposure and may suggest a more direct role for 25(OH)D in myopia pathogenesis.
Environmental factors are important in the development of myopia. There is still limited evidence as to whether computer use is a risk factor. The aim of this study is to investigate the association ...between computer use and myopia in the context of other near work activities.
Within the birth cohort study Generation R, we studied 5074 children born in Rotterdam between 2002 and 2006. Refractive error and axial length was measured at ages 6 and 9. Information on computer use and outdoor exposure was obtained at age 3, 6 and 9 years using a questionnaire, and reading time and reading distance were assessed at age 9 years. Myopia prevalence (spherical equivalent ≤–0.5 dioptre) was 11.5% at 9 years. Mean computer use was associated with myopia at age 9 (OR = 1.005, 95% CI = 1.001–1.009), as was reading time and reading distance (OR = 1.031; 95% CI = 1.007–1.055 (5–10 h/wk); OR = 1.113; 95% CI = 1.073–1.155 (>10 h/wk) and OR = 1.072; 95% CI = 1.048–1.097 respectively). The combined effect of near work (computer use, reading time and reading distance) showed an increased odds ratio for myopia at age 9 (OR = 1.072; 95% CI = 1.047–1.098), while outdoor exposure showed a decreased odds ratio (OR = 0.996; 95% CI = 0.994–0.999) and the interaction term was significant (P = 0.036). From our results, we can conclude that within our sample of children, increased computer use is associated with myopia development. The effect of combined near work was decreased by outdoor exposure. The risks of digital devices on myopia and the protection by outdoor exposure should become widely known. Public campaigns are warranted.
•Increased computer use is associated with myopia development before the age of 10 years.•Computer use was not as strongly associated as reading books.•The combined effect of all near work activities could be compensated by outdoor exposure.
The incidence of rhegmatogenous retinal detachment (RRD) is partly determined by its risk factors, such as age, sex, cataract surgery, and myopia. Changes in the prevalence of these risk factors ...could change RRD incidence in the population.
To determine whether the incidence of RRD in the Netherlands has changed over recent years and whether this change is associated with an altered prevalence of RRD risk factors.
This cohort study included data from all 14 vitreoretinal clinics in the Netherlands, as well as a large Dutch population-based cohort study. All patients who underwent surgical repair for a primary RRD in the Netherlands from January 1 to December 31, 2009, and January 1 to December 31, 2016, were analyzed, in addition to all participants in the population-based Rotterdam Study who were examined during these years. Analysis began February 2018 and ended November 2019.
RRD risk factors, including age, male sex, cataract extraction, and myopia.
Age-specific RRD incidence rate in the Dutch population, as well as change in RRD incidence and risk factor prevalence between 2009 and 2016.
In 2016, 4447 persons (median range age, 61 3-96 years) underwent surgery for a primary RRD within the Netherlands, resulting in an RRD incidence rate of 26.2 per 100 000 person-years (95% CI, 25.4-27.0). The overall RRD incidence rate had increased by 44% compared with similar data from 2009. The increase was observed in both phakic (1994 in 2009 to 2778 in 2016 increase, 39%) and pseudophakic eyes (1004 in 2009 to 1666 in 2016 increase, 66%), suggesting that cataract extraction could not solely account for the overall rise. Over the same period, the prevalence of mild, moderate, and severe myopia among persons aged 55 to 75 years had increased by 15.6% (881 of 4561 19.3% vs 826 of 3698 22.3%), 20.3% (440 of 4561 9.6% vs 429 of 3698 11.6%), and 26.9% (104 of 4561 2.3% vs 107 of 3698 2.9%), respectively, within the population-based Rotterdam Study.
In this study, an increase was observed in primary RRD incidence in the Netherlands over a 7-year period, which could not be explained by a different age distribution or cataract surgical rate. A simultaneous myopic shift in the Dutch population may be associated, warranting further population-based studies on RRD incidence and myopia prevalence.
Individuals with type 2 diabetes have increased fracture risk despite higher bone mineral density (BMD). Our aim was to examine the influence of glucose control on skeletal complications.
Data of ...4,135 participants of the Rotterdam Study, a prospective population-based cohort, were available (mean follow-up 12.2 years). At baseline, 420 participants with type 2 diabetes were classified by glucose control (according to HbA1c calculated from fructosamine), resulting in three comparison groups: adequately controlled diabetes (ACD; n = 203; HbA1c <7.5%), inadequately controlled diabetes (ICD; n = 217; HbA1c ≥ 7.5%), and no diabetes (n = 3,715). Models adjusted for sex, age, height, and weight (and femoral neck BMD) were used to test for differences in bone parameters and fracture risk (hazard ratio HR 95% CI).
The ICD group had 1.1-5.6% higher BMD, 4.6-5.6% thicker cortices, and -1.2 to -1.8% narrower femoral necks than ACD and ND, respectively. Participants with ICD had 47-62% higher fracture risk than individuals without diabetes (HR 1.47 1.12-1.92) and ACD (1.62 1.09-2.40), whereas those with ACD had a risk similar to those without diabetes (0.91 0.67-1.23).
Poor glycemic control in type 2 diabetes is associated with fracture risk, high BMD, and thicker femoral cortices in narrower bones. We postulate that fragility in apparently "strong" bones in ICD can result from microcrack accumulation and/or cortical porosity, reflecting impaired bone repair.
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