Dietary prevention of age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (ARMD) is the leading cause of blindness in people over the age of 65, and the prevalence of ARMD is expected to increase as the population ages. Although the incidence of ARMD increases sharply with age, recent studies indicate that prevention measures and dietary changes, implemented early in life, can reduce an individual's risk of ARMD. METHODS: Several dietary components have been proposed and studied with regard to their ability to protect against ARMD; these components include antioxidant vitamins and specific carotenoids. In particular, consumption of dark green, leafy vegetables has been shown in clinical studies to reduce the risk of ARMD. RESULTS: Biochemical studies of such vegetables have found that they contain several nutrients that may account for this effect, including high concentrations of the related carotenoids lutein and zeaxanthin. Structural and clinical studies have shown that these carotenoids are concentrated in the retinal macular pigment and that such accumulation is dependent on dietary intake. Further studies have indicated that the density of the macular pigment is related to preservation of visual sensitivity and (possibly) protection from ARMD. CONCLUSIONS: Large-scale clinical trials will be necessary to demonstrate that specific agents can reduce the incidence of ARMD. Nevertheless, specific dietary components--particularly, the carotenoids found in dark green, leafy vegetables--have shown great promise. While lifestyle modifications such as smoking cessation, reduction of alcohol consumption, and the wearing of sunglasses may reduce the risk of ARMD, it is likely that consumption of specific dietary components can reduce the risk further.     

Angiogenesis in early choroidal neovascularization secondary to age-related macular degeneration

Background: The morphological features of angiogenesis in early choroidal neovascularization secondary to age-related macular degeneration are yet to be fully described. Methods: Six eyes from five patients which on clinical and histological examination showed advanced age-related macular degeneration and early choroidal neovascularization have been studied by transmission electron microscopy. Results: Pre-existing choroidal capillaries and venules showed changes which included endothelial cell budding, pericyte enlargement, endothelial cell sprout formation and the development of intrachoroidal new vessels. In one case, an endothelial cell sprout continuous with an intrachoroidal vessel penetrated Bruch's membrane. Examination of early subretinal pigment epithelial new vessels showed them to spread between the inner layers of Bruch's membrane within the space usually occupied by the basal linear deposit and drusen. New vessel formation took place in blind pouches at the margins of new vessel networks, either in the absence of pericytes or in the presence of mainly myofibroblast-like pericytes. Conclusion: This ultrastructural study describes two phases of new vessel growth associated with the onset of choroidal neovascularization secondary to age-related macular degeneration. The initial intrachoroidal phase appears to be a low-turnover form of neovascularization which may lead to new vessels penetrating Bruch's membrane. Extensive subretinal pigment epithelial neovascularization, on the other hand, results from a high-turnover phase of neovascularization characterized by extensive endothelial cell proliferation and migration. Pericyte phenotypic changes associated with these different phases of neovascularization appear to relate to the dynamics of angiogenesis taking place in each process.     

Macular function in eyes with early age-related macular degeneration with or without contralateral late age-related macular degeneration

PURPOSE: To evaluate psychophysical and electrophysiologic responses in eyes with early age-related macular degeneration (AMD) without a decrease in visual acuity and with or without late AMD in the fellow eye. METHODS: Fifteen patients (mean age: 67.9 +/- 7.20 years) with early AMD in both eyes (AMD1 group, 15 eyes) and 15 patients (mean age: 71.40 +/- 7.06 years) with early AMD in one eye and late AMD in the fellow eye (AMD2 group, 15 eyes) were enrolled. They were compared to 15 age-similar normal control subjects. LogMAR visual acuity (VA), macular sensitivity by MP-1 microperimetry, and multifocal electroretinograms (mfERG) were assessed in control, AMD1, and AMD2 eyes. mfERG response amplitude density (RAD, nV/deg2) of the N1-P1 component of first order binary kernels was measured. RESULTS: When compared to controls, AMD1 and AMD2 eyes showed a significant (analysis of variance, P < 0.01) decrease in MP-1 microperimetry assessed in the 0-2.5 and 2.5-5 degrees of the macula, significantly correlated (Pearson test, P < 0.01) to the corresponding significant decrease (P < 0.01) in mfERG N1-P1 RADs assessed in the 0-2.5 and 2.5-5 degrees. In AMD1 and AMD2 eyes, VA and mfERG N1-P1 RADs assessed in the 5-20 degrees were similar (P > 0.01) to controls. VA, MP-1, and mfERG values were not significantly different in AMD1 and AMD2 eyes. CONCLUSION: In eyes with early AMD there is a dysfunction of preganglionic elements in the central 0-5 retinal degrees detectable by mfERG or MP-1 microperimetry. This impairment is not further influenced by the presence of late AMD in the fellow eye.     

Lack of benefit of early awareness to age-related macular degeneration

AIMS: To assess the rate of early awareness to the presence of age-related macular degeneration (AMD) and whether it enables early detection of transition to neovascular AMD (NVAMD) as compared with patients whose first presentation to an ophthalmologist is already at the neovascular stage of disease. METHODS: A retrospective analysis of 268 eyes of 268 consecutive patients with newly diagnosed NVAMD that were treated in a tertiary referral centre was performed. Patients were classified into those who were unaware (Group 1), or aware (Group 2), of the fact that they had AMD before diagnosis of NVAMD. Visual acuity, lesion size and composition, and demographics were compared between both groups. RESULTS: In all, 185 patients (69%) and 83 patients (31%) were classified to Groups 1 and 2, respectively. Patients in Groups 1 and 2 had similar demographic characteristics, presenting visual acuity and lesion size, and lesion compositions. Group 1 patients were more likely to have a positive history for smoking (41 vs26% in Group 2, P=0.03), whereas Group 2 patients were more likely to have positive family history for AMD (20 vs10%, P=0.02). Conclusions: These data suggest that current screening methods fail to identify the majority of patients with AMD before the development of NVAMD. The findings also demonstrate that in the routine clinical setting, prior awareness of AMD may not facilitate early detection of treatable choroidal neovascularization lesions.     

Multifocal pupillography identifies retinal dysfunction in early age-related macular degeneration

Background

Early age-related macular degeneration (AMD) is common among the elderly. While only a small number progress to sight-threatening stages of AMD, identifying prognostic functional markers remains paramount. Here, we objectively evaluate retinal function in patients with large drusen by multifocal pupillographic objective perimetry (mfPOP). Different temporal presentation rates and luminances were compared to optimize parameters for high signal to noise ratios (SNR) and diagnosticity for early AMD.

Methods

Pupil responses were recorded from 19 early AMD patients (30 eyes) and 29 age-matched control subjects. We compared a luminance-balanced stimulus ensemble and two unbalanced stimulus variants, each consisting of 44 independent stimulus regions per eye extending from fixation to 15? eccentricity. Video cameras recorded pupil responses for each eye under infrared illumination. The amplitudes and delays of the peak responses were analysed by multivariate linear models. The diagnostic accuracy of the stimulus variants was compared using areas under the curve (AUC) of receiver operator characteristic (ROC) plots.

Results

Early AMD eyes differed significantly from normal in their mean constriction amplitudes (?2.22?±?0.15 dB, t?=??14.8) and delays (17.92?±?1.2 ms, t?=?14.9). The brightest stimulus ensembles produced the highest median SNRs of 3.45 z-score units; however, the balanced method was found to be the most diagnostic. AUC values of 0.95?±?0.03 (mean ± SE) for early AMD were obtained when the asymmetry of response amplitudes between eyes was considered.

Conclusions

The mfPOP responses of early AMD eyes showed significant abnormality in response amplitudes and peak time. The ROC AUCs of 95 % suggest that mfPOP is a sensitive tool for detecting early abnormalities in AMD and longitudinal studies measuring progression of retinal dysfunction are warranted.     

Aspirin use and early age-related macular degeneration: a meta-analysis

Objective

The aim of this review was to evaluate the evidence for an association between Aspirin use and early age-related macular degeneration (ARMD).

Methods

A literature search was performed in 5 databases with no restrictions on language or date of publication. Four studies involving 10292 individuals examining the association between aspirin and ARMD met the inclusion criteria. Meta-analysis was carried out by Cochrane Collaboration Review Manager 5.2 software (Cochrane Collaboration, Copenhagen, Denmark).

Results

The pooled odd ratios showed that Aspirin use was associated with early ARMD (pooled odds ratio 1.43, 95% CI 1.09–1.88).

Conclusions

There is a small but statistically significant association between Aspirin use and early ARMD, which may warrant further investigation.     

吸烟与年龄相关性黄斑变性

吸烟是年龄相关性黄斑变性（AMD）最重要和唯一公认的可修正危险因素。吸烟可增加AMD的患病风险,促进病变发展,而且与一些遗传易感因素可能具有联合作用。其作用机制包括影响血流动力学、氧化损伤和促进新生血管形成等。吸烟在AMD发生发展中的重要作用使其成为AMD防治研究中关注的焦点之一。     

炎症与年龄相关性黄斑变性

年龄相关性黄斑变性(AMD)是中老年人常见的致盲性眼病之一,特征性改变是玻璃膜疣(drusen)形成和脉络膜新生血管(CNV),确切发病机制不清,衰老、营养失衡和遗传等多种因素参与其发病。近年来研究发现机体慢性炎症和补体活化等免疫机制在其发病中占有重要作用,从AMD患者病灶组织及玻璃膜疣中发现有巨噬细胞和补体成分沉积,玻璃膜疣的形成与补体成分在Bruch膜上的活化以及脉络膜巨噬细胞吞噬功能下调有关,CNV的形成与补体成分活化、炎症刺激以及脉络膜巨噬细胞聚集活化有关,补体因子H的基因多态性也与AMD的发生有关。脂褐素碎片可刺激视网膜色素上皮细胞活化并分泌炎性细胞因子或血管生长因子,促进CNV的形成;长期光氧化损伤可导致视网膜蛋白变性形成新抗原,并刺激机体产生自身抗体,导致补体活化和巨噬细胞聚集,参与玻璃膜疣的形成和CNV发生。综上证据表明慢性炎症和补体活化等免疫学改变在AMD发生中起着重要作用,这就提示抗炎治疗可作为AMD患者的有效辅助治疗措施。     

脂褐素与年龄相关性黄斑变性

年龄相关性黄斑变性(ARMD)是引起中老年人视力丧失的首要原因,其确切病因尚未明了,故治疗效果不佳。脂褐素随着年龄增长在视网膜色素上皮的积累是眼睛老化的标志,通过光化学作用等影响正常视网膜色素上皮细胞的功能,与ARMD的发生发展有一定联系。本文就脂褐素及其与ARMD的关系进行综述。     

老年黄斑变性中感光细胞的凋亡

目的 探讨细胞凋亡在老年黄斑病变性感光细胞死亡中的作用。方法 对１６只老年黄斑变性眼的黄斑部视网膜组织进行ＴＵＮＥＬ技术（ＴＤＴ－ｍｅｄｉａｔｅｄｂｉｏｔｉｎ－ｄＵＴＰｎｉｃｋ－ｅｎｄｌａｂｅｌｌｉｎｇ）和病理组织学研究。结果 本组中６只眼的黄斑病有细胞凋亡的特征性改变,分散排列的感光细胞核ＤＮＡ片断化。结论 细胞凋亡是老年黄斑变性中感光细胞死亡的一个重要机理。     

炎症与年龄相关性黄斑变性

近年来炎症与年龄相关性黄斑变性（AMD）的关系受到关注，主要包括与炎症相关的免疫分子与AMD的关系，如补体系统和炎症相关基因、单核细胞趋化蛋白（MCP）、C反应蛋白（CRP）等，以及炎症与AMD病理改变的关系如视网膜色素上皮细胞（RPE）损伤、玻璃膜疣以及脉络膜新生血管形成（CNV）等。     

Microperimetry and fundus autofluorescence in patients with early age-related macular degeneration

BACKGROUND: Early age-related macular degeneration (AMD) has been correlated with different functional alterations, but the exact relationship between fundus lesions and overlying sensitivity is not well known. The aim of this study was to compare fundus-related sensitivity (microperimetry) and fundus autofluorescence (FAF) of the macular area with drusen and pigment abnormalities in early AMD. METHODS: 13 consecutive patients with early AMD and visual acuity of 20/20 were studied by means of microperimetry, which automatically analyses macular light differential threshold and fixation patterns. Fundus colour photo and FAF of the macular area were recorded on the same day. Microperimetry was exactly (topographically) superimposed over FAF images. RESULTS: Macular sensitivity significantly decreased over large drusen (11.2 +/- 5.6 dB, p<0.0001) and over pigment abnormalities (13.1 +/- 3.6 dB, p<0.0001). When both characteristics were present the reduction was greater if compared with its absence (9.6 +/- 4.3 versus 15.0 +/- 4.5 dB, p<0.0001). Sensitivitity reduction was significant in areas with altered FAF when compared with areas with normal FAF (p<0.0001). CONCLUSIONS: Increased FAF in early AMD has a functional correlate exactly quantified by microperimetry. In retinal areas affected by early AMD retinal sensitivity deteriorates, despite good visual acuity. Microperimetry may allow the early detection of functional impairment caused by these lesions. Both microperimetry and FAF may be useful to monitor AMD progression.