Recent population-based studies have shown that retinal vascular caliber may predict the risk of clinical coronary artery disease (CAD) events. Whether this association is related to macro- or microvascular mechanisms remains unknown. We investigated the relationship of retinal vascular caliber with severity and extent of CAD in symptomatic cardiac patients.Overall, 98 patients attending diagnostic coronary angiography were recruited. Coronary angiography was used to assess for the severity and extent of CAD. Digital retinal photography was performed immediately prior to cardiac catheterization, and retinal vascular caliber was measured from these photographs by using a computer program and summarized as central retinal arteriolar (CRAE) and venular (CRVE) equivalents.Retinal arteriolar and venular calibers were not associated with increasing severity of CAD, as assessed by Leaman scores (CRAE/CRVE: P for trend=0.17/0.57), presence of clinically significant CAD (CRAE/CRVE: P=0.35/0.32), or number of diseased vessels (CRAE/CRVE: P for trend=0.18/0.69).Retinal vascular caliber changes are not associated with the severity of obstructive CAD in symptomatic patients. These data suggest that the association of retinal vascular caliber with clinical CAD seen in epidemiological studies may not be applicable to clinical symptomatic patients and may be related to microvascular, rather than macrovascular, mechanisms.
purpose. To describe the cross-sectional relationships between age, blood pressure (BP), and quantitative measures of retinal vessel diameters in an older Australian population. methods. Retinal photographs from right eyes of participants (n = 3654, aged 49+ years) in the Blue Mountains Eye study taken during baseline examinations (1992–1994) were digitized. The width of all retinal vessels located 0.5 to 1.0 disc diameters from the disc margin was measured by a computer-assisted method. Summarized estimates for central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) represent average retinal vessel diameters. The arteriole-to-venule ratio (AVR) was calculated. Associations between age and BP and CRAE, CRVE, and AVR were assessed with generalized linear models. results. Retinal vessel diameters decreased with increasing age in both men and women. CRAE and CRVE decreased by 4.8 μm and 4.1 μm, respectively, per decade increase in age, after adjusting for sex and mean arterial blood pressure. Mean AVR declined by 0.01 for each increasing decade of age, until 79 years. After adjustment for age, sex, smoking, and body mass index, CRAE, CRVE and AVR were all significantly and inversely associated with BP. For every 10-mm Hg increase in mean arterial blood pressure, AVR decreased by 0.012 and CRAE and CRVE decreased by 3.5 μm and 0.96 μm, respectively. conclusions. Retinal arteriolar and venular diameters narrow with increasing age, and these parameters are inversely related to BP, independent of age, gender, and smoking. The findings are consistent with those from the Atherosclerosis Risk in Communities Study suggesting that decreased retinal vessel diameters may reflect microvascular damage from elevated blood pressure.
Abstract Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7–15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E–08) and 2.3% (P = 6.9E–21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4 ; P = 6.3E–04).
The ATOH7 gene has been previously associated with glaucoma and glaucoma-related traits, such as disc size and cup/disc ratio (CDR). CDR is an important part of the glaucoma phenotype, whereas the relationship between the disc size and the disease is not well understood. The aim of this study was to investigate whether ATOH7 is associated independently with CDR or merely with the size of the optic disc.
Method
We carried out an association analysis for a candidate region, including ATOH7 for two populations: the Blue Mountains Eye Study and the TwinsUK cohort. We performed three linear regression models for (1) disc size adjusted on age, sex and intraocular pressure (IOP), (2) CDR adjusted on age, sex and IOP and (3) CDR adjusted on age, sex, IOP and disc size.
Results
A strong signal was found at rs7916697 for disc size. This single nucleotide polymorphism (SNP) was also associated with CDR adjusted on age, sex and IOP. However, this SNP was not associated with CDR when adjusted on age, sex, IOP and also disc size.
Conclusions
This study finds that ATOH7 is associated with optic disc size but not independently with CDR.
<i>Background:</i> Explanations for associations found between sensory and cognitive function remain unclear. <i>Objective:</i> To assess in an older Australian population: (1) the correlation between sensory and cognitive function across groups with a narrow age range; (2) any independent association between sensory and cognitive impairment. <i>Methods:</i> We examined 3,509 non-institutionalised residents aged 50+ years in the second cross-sectional survey of the Blue Mountains Eye Study (1997–2000). Visual impairment was defined for best-corrected visual acuity (VA) <6/12 in the better eye, moderate to severe hearing loss for hearing threshold >40 dB (better ear), and likely cognitive impairment for Mini-Mental State Examination (MMSE) <24 points. <i>Results:</i> We found likely cognitive impairment in 3.3%, vision impairment in 2.7% and moderate to severe hearing loss in 10.5% of this population. Correlation between VA or hearing threshold and MMSE score increased with age. After adjusting for age, weak but significant correlation was evident in the normal ageing sample between vision and MMSE (r = 0.12 with vision items included and r = 0.11 with vision items excluded, both p < 0.0001), and between hearing thresholds and MMSE (r = –0.12, p < 0.0001). After adjusting for age, sex, education and history of stroke, persons with vision impairment had a lower mean MMSE score than those with normal vision, regardless of whether vision-related items were included (27.1 vs. 28.6, p < 0.001) or excluded (19.8 vs. 21.0, p < 0.001). Similarly, persons with moderate to severe hearing loss had a lower mean MMSE score than those without hearing loss (28.1 vs. 28.7, p < 0.001). Persons with likely cognitive impairment also had lower mean VA and higher mean hearing threshold than those without, after adjustment. <i>Conclusions:</i> We have documented an age-related correlation between sensory and cognitive function in a normal ageing sample. The association between sensory impairment and likely cognitive impairment remained significant after excluding vision-related MMSE items and adjusting for confounding factors. Our data suggest that age-related decline and the effect of visual impairment on the measurement of cognition only partly explain the association between sensory and cognitive impairments in older persons.
Pseudoexfoliation syndrome is a major risk factor for the development of glaucoma. Following recent reports of a strong association of coding variants in the lysyl oxidase-like 1 (LOXL1) gene with this syndrome but low penetrance and variable disease frequency between different populations, we aimed to identify additional genetic factors contributing to the disease. The clusterin (CLU) gene has been proposed as a candidate because of the presence of clusterin protein in pseudoexfoliation deposits, its varied levels in aqueous humor of cases compared to controls, and the role of the protein as a molecular chaperone. We investigated the association of genetic variants across CLU in pseudoexfoliation syndrome and analyzed molecular characteristics of the encoded protein in ocular tissues.The expression of clusterin in relevant ocular tissues was assessed using western blotting. Nine tag single nucleotide polymorphisms (SNPs) across CLU were genotyped in 86 cases of pseudoexfoliation syndrome and 2422 controls from the Australian Blue Mountains Eye Study cohort. Each SNP and haplotype was assessed for association with the syndrome.Clusterin was identified in normal human iris, the ciliary body, lens capsule, optic nerve, and aqueous humor. Post-translational modification gives rise to a 100 kDa precursor protein in ocular tissues, larger than that reported in non-ocular tissues. One CLU SNP (rs3087554) was nominally associated with pseudoexfoliation syndrome at the genotypic level (p=0.044), although not when the age of controls was restricted to those over 73 years. Only age and the LOXL1 diplotype were significant factors in the logistic regression. One haplotype of all nine CLU SNPs was also associated (p=0.005), but the significance decreased slightly with the use of the age-restricted controls (p=0.011).Clusterin is present in ocular anterior segment tissues involved in pseudoexfoliation syndrome. Although one haplotype may contribute in a minor way to genetic risk of pseudoexfoliation syndrome, common variation in this gene is not a major contributor to the risk of pseudoexfoliation syndrome.
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