The association between statin use and risk of age-related macular degeneration.
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ABSTRACT:
SUBMITTER: Ma L
PROVIDER: S-EPMC4677306 | biostudies-other | 2015 Dec
REPOSITORIES: biostudies-other
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Project description:PURPOSE:To evaluate the association of statin use with progression of age-related macular degeneration (AMD). DESIGN:Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. PARTICIPANTS:Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50 to 85 years. METHODS:Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke-all known to be associated with statin use-were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses adjusting for the competing risk of death were also performed. MAIN OUTCOME MEASURES:Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). RESULTS:Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.83-1.41; P = 0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29). Furthermore, subgroup analyses of persons with or without late AMD at baseline and the various components of late AMD (neovascular AMD, central GA, or any GA) also showed no statistically significant association of statin use with progression to AMD. CONCLUSIONS:Statin use was not statistically significantly associated with progression to late AMD in the AREDS2 participants, and these findings are consistent with findings in the majority of previous studies. Statins have been demonstrated to reduce the risk of cardiovascular disease, but our data do not provide evidence of a beneficial effect on slowing AMD progression.
| S-EPMC4658271 | biostudies-literature
Project description:Importance:Amyloid-? is a major component of retinal drusen, the primary lesions of age-related macular degeneration (AMD), and autopsy and animal models suggested that anticholinergic drug (ACD) use increased brain amyloid-? deposition. Objective:To investigate the association between exposure to ACDs and late AMD (features of neovascular AMD or geographic atrophy of the retinal pigment epithelium in at least 1 eye). Design, Setting and Participants:A multicenter case-control study in 4 French ophthalmologic centers comprising 200 cases with late AMD and 200 controls enrolled from July 2016 to June 2017. Exposures:Exposure to at least 3 months of ACDs started before AMD diagnosis was recorded during a specific interview. A dose-effect association with cumulative exposure duration and Anticholinergic Burden Score was explored. The association between ACD exposure and AMD was assessed by multivariate logistic regression analysis adjusted for age, sex, smoking status, family history of AMD, alcohol consumption, and use of anticoagulant and anti-inflammatory drugs. Odds ratios (ORs) and 95% confidence intervals were estimated. Main Outcomes and Measures:Association between exposure to ACDs and late AMD. Results:Among case participants, the mean (SD) age was 74.8 (9.2) years, 129 (64.5%) were women, 192 (96%) were white, 65 (32.5%) had geographic atrophy, 135 (67.5%) had neovascular AMD, 116 (58%) had unilateral AMD, and 84 (42%) had bilateral AMD. Among control participants, the mean (SD) age was 75.5 (7.2) years, with 116 (58%) women and 187 (93.5%) white participants. Twenty-six cases (13%) and 10 controls (5%) were exposed to ACDs throughout life for at least 3 months before AMD onset. Risk of AMD was increased with ever exposure to ACDs (adjusted OR [aOR], 2.84; 95% CI, 1.33-6.06; P?=?.007), high Anticholinergic Burden Score (?3) (aOR, 6.42; 95% CI, 1.38-29.92; P?=?.02), and longest cumulative exposure to ACD (?15 years) (aOR, 5.88; 95% CI, 1.22-28.31; P?=?.03). Conclusions and Relevance:Risk of late AMD may be increased with at least 3 months' use of ACDs. A dose-effect association was suggested by a greater association with prolonged use and high Anticholinergic Burden Score. Further studies, in particular those with longitudinal design, are needed to confirm this association.
| S-EPMC6136046 | biostudies-literature
Project description:Deficient 25-hydroxyvitamin D (25[OH]D) concentrations have been associated with increased odds of age-related macular degeneration (AMD).To examine whether this association is modified by genetic risk for AMD and whether there is an association between AMD and single-nucleotide polymorphisms of genes involved in vitamin D transport, metabolism, and genomic function.Postmenopausal women (N?=?913) who were participants of the Carotenoids in Age-Related Eye Disease Study (CAREDS) (aged 54 to <75 years) with available serum 25(OH)D concentrations (assessed October 1, 1993, to December 31, 1998), genetic data, and measures of AMD (n?=?142) assessed at CAREDS baseline from May 14, 2001, through January 31, 2004, were studied.Prevalent early or late AMD was determined from graded, stereoscopic fundus photographs. Logistic regression was used to estimate odds ratios (ORs) and 95% CIs for AMD by the joint effects of 25(OH)D (<12, ?12 to <20, ?20 to <30, and ?30 ng/mL) and risk genotype (noncarrier, 1 risk allele, or 2 risk alleles). The referent group was noncarriers with adequate vitamin D status (?30 ng/mL). Joint effect ORs were adjusted for age, smoking, iris pigmentation, self-reported cardiovascular disease, self-reported diabetes status, and hormone use. Additive and multiplicative interactions were assessed using the synergy index (SI) and an interaction term, respectively. To examine the association between AMD and variants in vitamin D-related genes, age-adjusted ORs and 95% CIs were estimated using logistic regression.Among the 913 women, 550 had adequate levels of vitamin D (?20 ng/mL), 275 had inadequate levels (?12 to <20 mg/mL), and 88 had deficient levels (<12 ng/mL). A 6.7-fold increased odds of AMD (95% CI,?1.6-28.2) was observed among women with deficient vitamin D status (25[OH]D <12 ng/mL) and 2 risk alleles for CFH Y402H (SI for additive interaction,?1.4; 95% CI,?1.1-1.7; P for multiplicative interaction?=?.25). Significant additive (SI,?1.4; 95% CI,?1.1-1.7) and multiplicative interactions (P?=?.02) were observed for deficient women with 2 high-risk CFI (rs10033900) alleles (OR,?6.3; 95% CI,?1.6-24.2). The odds of AMD did not differ by genotype of candidate vitamin D genes.In this study, the odds of AMD were highest in those with deficient vitamin D status and 2 risk alleles for the CFH and CFI genotypes, suggesting a synergistic effect between vitamin D status and complement cascade protein function. Limited sample size led to wide CIs. Findings may be due to chance or explained by residual confounding.
| S-EPMC4841267 | biostudies-literature
Project description:OBJECTIVE:Pigment epithelium-derived factor (PEDF) strongly inhibits angiogenesis, and plays an important role in retinoblastoma cells. In this study we detect the association of PEDF gene polymorphisms (rs1136287 and rs12150053) and age-related macular degeneration (AMD) risk. METHODS:This is a case-control study including 118 AMD patients and 121 healthy controls. PEDF gene polymorphisms were genotyped by TaqMan method. Hardy-Weinberg equilibrium (HWE) was used to detect the representativeness of the cases and controls. Differences of genotype and allele distributions of PEDF polymorphisms were calculated by Chi-square test. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were used to present the relative risk of AMD. RESULTS:Genotype and allele distributions in controls were in accordance with HWE. Genotype and allele distributions of rs1136287 had no significant association with the susceptibility of AMD under five contrast models (P<0.05). CC genotype and C allele of rs12150053 were higher in cases than that in controls, and rs12150053 was obviously related to the risk of AMD under T vs. C model (P=0.044, OR=1.499, 95% CI=1.009-2.226). CONCLUSION:In this study, there was no obvious association between PEDF gene rs1136287 polymorphism and AMD susceptibility, and rs12150053T might act as a susceptible allele in the occurrence of AMD.
| S-EPMC6966057 | biostudies-literature
Project description:BACKGROUND: Age-related macular degeneration (AMD) is the main cause of blindness and the curative options are limited. The objective of this meta-analysis was to determine the association between aspirin use and risk of AMD. METHODS: A comprehensive literature search was performed in PubMed, Embase, Web of Science, and reference lists. A meta-analysis was performed by STATA software. RESULTS: Ten studies involving 171,729 individuals examining the association between aspirin use and risk of AMD were included. Among the included studies, 2 were randomized-controlled trials (RCTs), 4 were case-control studies and 4 were cohort studies. The relative risks (RRs) were pooled using a random-effects model. Relative risks with 95% confidence intervals (CIs) of aspirin use as a risk for AMD. The pooled RR of 10 included studies between the use of aspirin and risk of AMD was 1.09 (95% CI, 0.96-1.24). The same result was detected in early and late stage AMD subgroup analysis. In the subgroup analyses, the pooled RR of RCTs, case-control studies and cohort studies were 0.81 (95% CI, 0.64-1.02), 1.02 (95% CI, 0.92-1.14) and 1.08 (95% CI, 0.91-1.28), respectively. CONCLUSIONS: The use of aspirin was not associated with the risk of AMD.
| S-EPMC3597550 | biostudies-other
Project description:Lipid metabolism may be involved in the pathogenic mechanism of age-related macular degeneration (AMD). However, conflicting results have been reported in the associations of AMD with blood lipids. We performed a meta-analysis including a total of 19 studies to evaluate associations between blood lipids and this disease. The result reported that the high level of high-density lipoprotein cholesterol (HDL-C) obtained with an increment of 1 mmol/L could result in a significantly increase in the AMD risk of approximately 18% (relative risk (RR), 1.18; 95% confidence interval (CI), 1.01 to 1.35; I² = 53.8%; p = 0.007). High levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were significantly associated with a decreased risk of AMD (RRs ranging from 0.92 to 0.95; all p < 0.05). The stratified analysis based on AMD subtypes showed that these blood lipids were only significantly associated with the risk of early AMD (all p < 0.05). The association between the blood lipids and AMD risk did not differ substantially based on the other characteristics of the participants. A high HDL-C level was associated with an increased AMD risk, whereas participants with high TC, LDL-C, and TG concentrations may show a decreased risk for this disease. Further well-designed large studies are warranted to confirm the conclusions.
| S-EPMC5084049 | biostudies-literature
Project description:CFH and HTRA1 genes are traditional markers of increased risk of age-related macular degeneration (AMD) across populations. Recent findings suggest that additional genes-for instance, in the dystrophin-associated protein complex-might be promising markers for AMD. Here, we performed a case-control study to assess the effect of SGCD single nucleotide polymorphisms (SNPs), a member of this protein family, on AMD diagnosis and phenotype. We performed a case-control study of an under-studied population from Hispanics in Mexico City, with 134 cases with 134 unpaired controls. Cases were 60 years or older (Clinical Age-Related Maculopathy Staging (CARMS) grade 4?5, as assessed by experienced ophthalmologists following the American Association of Ophthalmology (AAO) guidelines), without other retinal disease or history of vitreous-retinal surgery. Controls were outpatients aged 60 years or older, with no drusen or retinal pigment epithelium (RPE) changes on a fundus exam and a negative family history of AMD. We examined SNPs in the SGCD gene (rs931798, rs140617, rs140616, and rs970476) by sequencing and real-time PCR. Genotyping quality checks and univariate analyses were performed with PLINK v1.90b3.42. Furthermore, logistic regression models were done in SAS v.9.4 and haplotype configurations in R v.3.3.1. After adjusting for clinical covariates, the G/A genotype of the SGCD gene (rs931798) significantly increases the odds of being diagnosed with AMD in 81% of cases (1.81; 95% CI 1.06?3.14; p = 0.031), especially the geographic atrophy phenotype (1.82; 95% CI 1.03?3.21; p = 0.038) compared to the G/G homozygous genotype. Moreover, the GATT haplotype in this gene (rs931798, rs140617, rs140616, and rs970476) is associated with lower odds of AMD (adjusted odds ratio (OR) 0.13; 95% CI 0.02?0.91; p = 0.041). SGCD is a promising gene for AMD research. Further corroboration in other populations is warranted, especially among other Hispanic ethnicities.
| S-EPMC6210939 | biostudies-literature
Project description:ImportanceRecent reports suggest that cilioretinal arteries (CRAs) confer protection against developing advanced age-related macular degeneration (AMD).ObjectiveTo further characterize the association between the presence of a CRA and incidence of geographic atrophy (GA) or choroidal neovascularization (CNV).DesignThis cohort study constituted an ad hoc secondary analysis of data from the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) and was performed at 44 clinical centers in the United States among participants in CATT with CNV in the study eye and without advanced AMD in the fellow eye at baseline. The presence of a CRA was determined by 2 graders, masked to clinical data, using color fundus photographs, red-free fundus photographs, and fluorescein angiography. The proportion with CRAs at baseline between the study eye with CNV and fellow eye without CNV was first compared. The association of a CRA with incidence of CNV or GA at 5 years among fellow eyes and with incidence of GA among study (treated) eyes was then assessed. In addition, the association of CRAs with the Age-Related Eye Disease Study severity scale among the fellow eyes at baseline was assessed. Data were collected from February 1, 2008, through April 30, 2015, and analyzed from July 1, 2018, through April 30, 2019.ExposuresPresence of a CRA.Main outcomes and measuresThe association between the presence of a CRA and incidence of CNV or GA at 5 years of follow-up.ResultsA total of 350 patients (700 eyes) (230 [65.7% women; mean [SD] age, 77 [7.2] years) were included in the analysis. Cilioretinal arteries were present in 67 of 345 (19.4%) fellow eyes without baseline CNV and 73 of 349 (20.9%) study eyes with baseline CNV (P = .60). Cilioretinal arteries in fellow eyes were not associated with incidence of CNV at 5 years (125 of 278 [45.0%] among eyes without CRAs and 30 of 67 [44.8%] among eyes with CRAs; P = .99) or with incidence of GA at 5 years (110 of 278 [39.6%] among eyes without CRAs and 25 of 67 [37.3%] among eyes with CRAs; P = .89). Cilioretinal arteries in study eyes were not associated with incidence of GA at 5 years (105 of 276 [38.0%] study eyes without CRAs and 26 of 73 [35.6%] study eyes with CRAs; P = .72).Conclusions and relevanceThe analysis did not find a protective association between CRAs and incidence of CNV or GA among CATT participants who had unilateral exudative AMD. Why these findings were different from those of previous publications is unclear but may be partially explained by the different techniques used to detect CRAs or by the baseline advanced disease in CATT participants.Trial registrationClinicalTrials.gov identifier: NCT00593450.
| S-EPMC6743058 | biostudies-literature
Project description:Age-related macular degeneration (AMD) is a degenerative and progressive disease of the macula, the part of the retina that is responsible for central vision. AMD shares some risk factors with diabetes mellitus (DM), but little is known about the risk of DM in individuals with AMD. With the goal of establishing novel perspectives, this study aimed to investigate the association between AMD and the risk of DM using the Korean Nationwide Health Insurance Database. Individuals aged ≥ 50 years who underwent a national health screening program in 2009 were enrolled. Participants were categorized by the presence of AMD and visual disability (VD). The Cox hazard regression model was used to examine hazard ratios (HRs) of DM with adjustment for potential confounders. Stratified analyses by age, sex, and comorbidities (hypertension or dyslipidemia) were also performed. During a mean follow-up of 8.61 years, there were 403,367 (11.76%) DM incidences among the final 3,430,532 participants. The crude HR (95% confidence interval (CI)) was 1.16 (1.13-1.20) for AMD. After adjusting for potential confounders, AMD was associated with a 3% decreased risk of DM (aHR 0.97, 95% CI 0.95-1.00), but no significant association with the risk of DM was found in AMD with VD (aHR 1.03, 95% CI 0.93-1.14). In summary, we did not find an increased risk of DM in individuals with AMD. A 3% decreased risk of DM in patients with AMD is not clinically meaningful. Our study suggests that the association between AMD and the risk of DM is weak, considering the potential confounders. Further studies examining this association are needed to extend our knowledge.
| S-EPMC9599121 | biostudies-literature
Project description:ObjectivesTo investigate the effect of metformin on the decreased risk of developing age-related macular degeneration (AMD) in patients with type 2 diabetes mellitus (T2DM) for ≥10 years.DesignA retrospective study.ParticipantsPatients aged ≥50 with a diagnosis of T2DM no less than 10 years were included.MethodsVariables predisposing to AMD were reviewed; the potential confounders related to T2DM or AMD were selected from literature records; AMD and diabetic retinopathy (DR) were diagnosed by funduscopy, optical coherence tomography and/or fluorescein angiography. The subgroup analysis was performed in early and late AMD. The protective effect of metformin was evaluated in duration-response and dose-response patterns.ResultsA total of 324 patients (115 metformin non-users and 209 users) were included in the final analysis. AMD was observed in 15.8% of metformin users and 45.2% of metformin non-users (p<0.0001). The ORs for any AMD, early AMD and late AMD present in patients with DR were 0.06 (0.02-0.20), 0.03 (0.00-0.20) and 0.17 (0.04-0.75). The serum high-density lipoprotein level was positively associated with the late AMD risk (p=0.0054). When analysed by the tertiles of cumulative duration, a similarly reduced risk was observed for the second (5-9 years) (OR: 0.24, 95% CI: 0.08 to 0.75) and third tertiles (≥10 years) (OR: 0.22, 95% CI: 0.09 to 0.52) compared with the first tertile (≤4 years).ConclusionAmong patients with T2DM for ≥10 years, metformin users were less likely to develop any AMD and early AMD than non-users; however, the late AMD was not significantly associated with the use of metformin. Also, AMD was less prevalent in patients with DR. The prolonged metformin treatment with a high cumulative dose enhanced the protective effect against AMD. Metformin significantly reduces the AMD risk when the cumulative duration is >5 years.
| S-EPMC9045056 | biostudies-literature