A case control study of age related macular degeneration and use of statins

AIMS: Age related macular degeneration (AMD) is the leading cause of blindness in industrialised countries. Previous studies have suggested that statins may have a protective effect against the disease; however, existing studies have had limited power to reliably detect or exclude an effect and have produced conflicting results. The authors assessed the risk of AMD associated with the use of statins. METHODS: Population based case control study using the United Kingdom General Practice Research Database. 18 007 people with diagnosed AMD were compared with 86 169 controls matched on age, sex, and general practice. The primary outcome was the odds ratio for the association between exposure to statins and AMD. RESULTS: The crude odds ratio for the association between any recorded exposure to statins and AMD was 1.32 (95% CI 1.17 to 1.48), but this reduced to 0.93 (95% CI 0.81 to 1.07, p=0.33) after adjustment for consultation rate, smoking, alcohol intake, body mass index, atherosclerotic disease, hyperlipidaemia, heart failure, diabetes mellitus, hypertension, use of other cardiovascular drugs, and use of fibrates. There was no evidence that the risk varied by dose of statin, duration of use, or that the risk varied for individual statins. CONCLUSION: In the short and medium term statin use is not associated with a decreased risk of AMD. Whether subgroups of patients with specific forms of AMD (particularly choroidal neovascularisation) benefit from statin therapy remains a possibility.     

Morphopathological study in age related macular degeneration

The aim of this paper is to study the morphopathological changes manifested in age-related macular degeneration. MATERIAL AND METHOD: The researched histopathological material consisted in two eye balls enucleated because of irreversible eye diseases from aged persons suffering from age-related macular degeneration. The method applied for processing the material was inclusion in paraffin, followed by usual coloration with hematoxylin-eosin. RESULTS AND CONCLUSIONS: The established changes (hard drusen, soft drusen, calcified drusen, changes of Bruch's membrane, subretinal neovascularization, serous retinal pigment epithelial detachment, disciform degeneration) prove the importance of Bruch's membrane in the pathogenesis of age-related macular degeneration.     

脂褐素和年龄相关黄斑变性的研究进展

年龄相关黄斑变性(age related macular degeneration，AMD)是目前影响老年人视力和生存质量的主要眼科疾病之一，对其缺乏有效的治疗手段，发病机制也不明。近年来对AMD研究表明，一种年龄相关的色素——脂褐素和其核心成分N-亚视黄基-N-视黄基-乙醇胺(N-retinyl—N-retinylidene ethanol amine，A2-E)在AND的发生和发展中有重要作用，它们随年龄增长而沉积于视网膜下，并可能通过慢性光化学作用损伤局部视网膜和脉络膜，从而导致AMD的发生。本研究着重阐述两者间的关系。     

老年黄斑变性的分子遗传学研究进展

老年黄斑变性(AMD)在西方发达国家是老年人视力损害的主要原因，在我国其发病率也有上升的趋势。AMD是一种复杂的疾病，虽然其发病机制尚不明确，但一些环境危险因素已得到证实。近来一些研究表明其可能在AMD的发病中起着重要的作用。ABCR、VMD2、TIMP3、ApoE、DHRD作为候补基因已开展研究，但研究结果尚存在争议。当前ABCR基因—Stargardt病的致病基因，成为研究的热点。的分子遗传学研究对于确定AMD的发病机制有重要作用。虽然遗传因素对于AMD的确切作用目前尚不明确，但AMD对老年黄斑变性的分子遗传研究进展进行综述。     

Association study of detoxification genes in age related macular degeneration

BACKGROUND/AIMS: Age related macular degeneration (AMD) is a complex disorder leading to loss of central vision, and identification of risk factors associated with susceptibility to AMD has been a key objective for ophthalmic genetics research for almost a decade. This association study has examined genetic polymorphisms in 12 candidate genes as possible risk factors for predisposition to the development of the exudative variant of AMD in a Northern Irish population. The choice of genes was based on their function in the breakdown of industrial pollutants, cigarette smoke, defence against oxidative stress, or involvement in the general ageing process. METHODS: Up to five single nucleotide polymorphisms (SNPs) were typed for CYP1A1, CYP1A2, CYP2E1, CYP2D6, EPHX1, MnSOD, AhR, NAT2, CAT, GPX1, PON1, and ADPRT1 by multiplex snapshot single base primer extension method. Genes showing high linkage disequilibrium (LD) between SNPs were analysed by haplotype analysis. Genes showing low LD were assessed using individual SNPs based on genotypes. RESULTS: After correction for number of genes/SNPs tested, no significant association with AMD was found although several genes merit further investigation. This study suggests that a coding SNP in EPHX1 (Y113H) may be important in AMD and supports a previous observation of an association with exudative AMD. In addition, haplotype analysis highlighted ADPRT1, CYP2D6, and AhR as worthy of further study. CONCLUSION: This study has identified a number of genes requiring further investigation including EPHX1, ADPRT1, CYP2D6, and AhR.     

A vision specific functional index for use in patients with age related macular degeneration

AIM: To develop and evaluate a new vision specific functional index for use in individuals with age related macular degeneration (AMD). METHODS: Following consultation with patients with AMD and healthcare professionals, a questionnaire entitled the Daily Living Tasks Dependent on Vision (DLTV) was constructed. It was administered by interview to three separate groups of individuals aged 50 years or older: people with AMD, people with cataract, and people with no visual disability. The relations between DLTV, distance visual acuity, and disorder were examined using Pearson's product moment correlation coefficients, stepwise regression, and principal component analysis. RESULTS: There was a positive correlation between DLTV items and distance visual acuity in the better eye. Principal component analysis showed that the DLTV has a major single dimension within it. This first principal component accounted for 59% of the variation and correlated well with distance visual acuity in the better eye. Other components were found, one of which correlated with the difference in vision in the two eyes and one which featured in the differentiation of AMD subjects from individuals with cataracts. CONCLUSIONS: The DLTV provided information on visual impairment in patients over and above that obtained from a measure of visual acuity. It also showed that patients with AMD experience greater difficulty with daily living tasks for any given level of acuity than do patients with cataract.     

New aspects in age related macular degeneration

Being the leading cause of blindness in modern world Age Related Macular Degeneration has beneficiated in the last decade of important progress in diagnosis, classification and the discovery of diverse factors who contribute to the etiology of this disease. Treatments have arised who can postpone the irreversible evolution of the disease and thus preserve vision. Recent findings have identified predisposing genetic factors and also inflamatory and imunological parameters that can be modified trough a good and adequate prevention and therapy This articole reviews new aspects of patology of Age Related Macular Degeneration like the role of complement in maintaining inflamation and the role of oxidative stress on different structures of the retina.     

老年黄斑变性的治疗研究进展

老年黄斑变性是一种严重威胁老年人视功能的眼底疾病,针对其危险因素、早期诊断及治疗,国内外展开了大量的研究。本文将总结近年来国内外对老年黄斑变性的新的治疗手段和方法。     

Metabolic physiology in age related macular degeneration

Ischemia and hypoxia have been implicated in the pathophysiology of age related macular degeneration (AMD). This has mostly been based on studies on choroidal perfusion, which is not the only contributor to retinal hypoxia found in AMD eyes. Other features of AMD may also interfere with retinal oxygen metabolism including confluent drusen, serous or hemorrhagic retinal detachment, retinal edema and vitreoretinal adhesion. Each of these features contributes to retinal hypoxia: the drusen and retinal elevation by increasing the distance between the choriocapillaris and retina; vitreoretinal adhesion by reducing diffusion and convection of oxygen towards and vascular endothelial growth factor (VEGF) away from hypoxic retinal areas. Hypoxia-inducible-factor is known to exist in subretinal neovascularization and hypoxia is the main stimulus for the production of VEGF. Each feature may not by itself create enough hypoxia and VEGF accumulation to stimulate wet AMD, but they may combine to do so. Choroidal ischemia in AMD has been demonstrated by many researchers, using different technologies. Choroidal ischemia obviously decreases oxygen delivery to the outer retina. Confluent drusen, thickening of Bruch's membrane and any detachment of retina or retinal pigment epithelium, increases the distance between the choriocapillaris and the retina and thereby reduces the oxygen flux from the choroid to the outer retina according to Fick's law of diffusion. Retinal elevation and choroidal ischemia may combine forces to reduce choroidal oxygen delivery to the outer retina, produce retinal hypoxia. Hypoxia leads to production of VEGF leading to neovascularization and tissue edema. A vicious cycle may develop, where VEGF production increases effusion, retinal detachment and edema, further increasing hypoxia and VEGF production. Adhesion of the viscous posterior vitreous cortex to the retina maintains a barrier to diffusion and?convection currents in the vitreous cavity according to the laws of Fick's, Stokes-Einstein and Hagen-Poiseuille. If the vitreous is detached from the surface of the retina, the low viscosity fluid transports oxygen and nutrients towards an ischemic area of the retina, and cytokines away from the retina, at a faster rate than through attached vitreous gel. Vitreoretinal adhesion can exacerbate retinal hypoxia and accumulation of cytokines, such as VEGF. Vitreoretinal traction can also cause hypoxia by retinal elevation. Conceivably, the basic features of AMD, drusen, choroidal ischemia, and vitreoretinal adhesion are independently determined by genetics and environment and may combine in variable proportions. If the resulting hypoxia and consequent VEGF accumulation crosses a threshold, this will trigger effusion and neovascularization.     

年龄相关性黄斑变性发病机制的研究进展

年龄相关性黄斑变性(age related macular degeneration,AMD)是引起中老年严重视力丧失最主要的原因。尽管进行了大量的基础和临床研究,其发病机制仍不清楚,大多数学者认为这是一种多因素疾病。我们概述了国内外有关AMD最新研究结果,为进一步探索AMD潜在的发生机制提供依据和方向。     

年龄相关性黄斑变性危险因素病例对照研究

目的 探讨年龄相关性黄斑变性(简称AMD)发生的可能相关危险因素.方法 应用成组对照的病例对照研究方法.病例组为AMD患者85例,选取医院中非AMD患者i00例作为对照组,均进行标准问卷调查及相关眼科检查,收集有关人口统计信息及危险因素的暴露史.采用)x2检验和多因素非条件Logistic逐步回归模型进行分析,筛选AMD的主要危险因素.结果 进行Logistic逐步回归分析,最终进入模型的因素有吸烟(X1)、抗氧化剂摄入(X2)、高血压(X3),建立回归方程为:ln[P/(1-P)]=-0.485+0.778 X1-0.897 X2+0.694 X3.多因素分析发现,吸烟(OR=2.177,95%CI=1.167～4.062)和高血压(OR=2.001,95%CI=1.063～3.766)为AMD发生的危险因素;经常服用抗氧化剂(OR=0.408,95%CI=0.200～0.832)为AMD发生的保护因素.趋势性检验发现吸烟与AMD的优势比之间存在一定的剂量反应关系.结论 AMD是多因素综合作用所致,吸烟及高血压会增加患AMD危险性,抗氧化剂的使用会减少患AMD的危险性.     

Case-control study of the risk factors for age related macular degeneration

AIM—A case-control study was initiated to determine the risk factors for the development of age related macular degeneration (AMD).METHODS—Study participants, who were all white, aged 50-85 years, and were recruited from private ophthalmology practices. Each practitioner enrolled patients with bilateral AMD, who were then matched with controls for sex and age. Environmental factors and systemic and ocular histories were screened. All patients had bilateral red-free fundus photographs and fluorescein angiography. Photographs were classified into pigment epithelium alterations, drusen, geographic atrophy, and exudative AMD. Statistical analysis included the identification of risk factors for AMD. A multivariate analysis was performed at the end of the study. Analysis included the entire study population and was carried out for each stage of AMD.RESULTS—1844 controls were compared with 1844 patients with AMD. Mean age was 71 years for controls and 72 for cases. Logistic regression identified six major risk factors for AMD (whole population): arterial hypertension (odds ratio (OR) =1.28), coronary disease (OR=1.31), hyperopia (OR=1.33), light coloured irises (OR=1.22), and lens opacities or previous cataract surgery (OR=1.55). The significance of vascular risk factors was increased for late stages of AMD, especially the atrophic forms (coronary disease, OR=3.19).CONCLUSIONS—This large case-control study confirms some of the risk factors previously identified and may contribute to the determination of methods for prevention of AMD.     

Review of genetics in age related macular degeneration

Age-related macular degeneration (AMD) is a degenerative disease of the retina and the leading cause of blindness in industrialized countries. AMD is a complex disease caused by the combination of genetic predisposition and environmental factors. The prevalence of AMD increases with age. The adverse effect of smoking is well established. Genetic predisposition has been demonstrated by familial aggregation studies and twin studies. Using genome linkage scan and association studies, multiple potentially causative genes have been identified. The chromosomes most commonly implicated are 1q25-31 and 10q26. In particular, variants in the gene for the complement factor H (CFH) and the genes PLEKHA1/LOC387715/HTRA1, Factor B (BF) and complement component 2 (C2) have been implicated as major risk or protective factors for the development of AMD. There have been some advances in the treatment of this condition; however, a complete cure remains remote but hopeful. Understanding the causative environmental and genetic interactions will facilitate the development of future preventive methods and treatments.