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.     

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.     

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.     

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.     

Statin use and the five-year incidence and progression of age-related macular degeneration

PURPOSE: To examine the association of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) with the five-year incidence of age-related macular degeneration (AMD). DESIGN: Population-based cohort study. METHODS: settings: Beaver Dam, Wisconsin. study population: Participants included persons 53 to 96 years of age at examination in 1998 to 2000 (n = 2,962), of whom 2,204 participated in a follow-up five years later. observation procedures: Standardized procedures were used for physical examinations, blood collection, and questionnaire administration. AMD was determined by grading images of the posterior pole using a standard protocol. Standard univariate and multivariate analyses were performed. main outcome measures: Incident early and late AMD and progressed AMD. RESULTS: There were 1,347 and 1,638 persons not using statins and 339 and 429 using statins at the 1998 to 2000 examination at risk of early and late AMD, respectively. The unadjusted five-year incidence of early and late AMD, respectively, was 5.9% and 1.8% in those not using statins and 6.8% and 2.3% in those using statins. While controlling for age, gender, smoking status, and multivitamin use, a history of statin use was not associated with the five-year incidence of early AMD (odds ratio [OR] 1.16, 95% confidence interval [CI] 0.71 to 1.91, P = .55), progression of AMD (OR 1.16, 95% CI 0.75 to 1.78, P = .51) or incidence of late AMD (OR 1.27, 95% CI 0.60 to 2.69. P = .53). CONCLUSION: These findings do not show an association between statin use and the incidence or progression of AMD over a five-year period.     

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.     

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.     

Case selection in macular relocation surgery for age related macular degeneration

BACKGROUND: To date there has been no randomised controlled trial demonstrating the safety and efficacy of macular relocation surgery (MRS) for age related macular degeneration (AMD). Vision can be improved in some patients and made worse in others despite successful surgery or because of complications. PURPOSE: To determine which patients would benefit from MRS. METHODS: Twenty nine patients with exudative AMD took part in a prospective, non-comparative, interventional study. Macular relocation surgery involved phacoemulsification, vitrectomy, 360 degrees retinotomy, excision of choroidal neovascular membrane, and macular relocation using an infusion of 5-fluorouracil and low molecular weight heparin as adjuvant to prevent proliferative vitreoretinopathy. Patients underwent protocol refraction preoperatively and six-monthly postoperatively by designated optometrists. Preoperative fundus fluorescein angiograms were read by masked observers and the lesions were classified according to a set protocol. The main outcome measures were visual improvement, final vision of better than 20/400, reading speed, critical print size. Logistic and multiple stepwise linear regressions were used to identify independent factors which predicted the main outcomes. RESULTS: Preoperative visual acuity (20/120 or worse) and lesion type (predominantly classic or submacular haemorrhage) were significantly associated with visual improvement (coefficient of regression B = 26.8, p<0.001 and B = 14.9 with p = 0.045 respectively). There were no significant independent factors which predicted a final distance logMAR visual acuity of 1.3 (20/400) or any arbitrary definition of blindness. CONCLUSIONS: The study showed that it was possible to select cases that were more likely to experience an improvement in vision following MRS.     

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。     

Future methods of trreatment in age related macular degeneration

In the present time the treatment of Age Related Macular Degeneration (ARMD) begins to develop. Many medical therapies are presently tested in the two types of ARMD, geographic atrophy and exudative ARMD. In atrophic ARMD, new drugs are aimed to spare photoreceptors and the retinal pigment epithelium, to prevent oxidative damage on the retina and to suppress the inflammation process. In exudative ARMD, new therapies are already in use and in progress, especially the anti-VEGF factors, and others try to improve visual prognosis in targeting other mechanism or cells involved in the angiogenesis process. This article reviews and summarizes the available data, presented in several scientific meetings, congresses or given directly by the companies involved.     

Choroidal perfusion perturbations in non-neovascular age related macular degeneration

AIM: Choroidal perfusion, affected in age related macular degeneration (AMD), is difficult to objectively assess given the overlying retinal circulation. This study more objectively compared choroidal perfusion parameters in a group with non-neovascular AMD to an unaffected age matched control group. METHODS: 21 non-neovascular AMD subjects and 21 age matched control subjects without evidence of AMD underwent assessment of their choroidal blood flow in a case-control study. Scanning laser ophthalmoscope indocyanine green (ICG) angiograms were analysed by a new area dilution analysis technique. Four areas in the perifoveal region and two areas in the temporal peripapillary retina were evaluated by producing a graph of intensity of fluorescence of each area over time. The mean of the filling times and the heterogeneity of the filling times were assessed. RESULTS: The means of the filling times within the perifoveal regions and the hetereogeneity of the filling times between regions within the same eyes were significantly greater in the AMD patients compared with the control subjects. CONCLUSIONS: Delayed and heterogeneous filling of the choroid was objectively demonstrated in eyes with non-neovascular AMD compared with age matched controls without evidence of AMD, using an area dilution analysis technique applied to ICG angiography.