TLR3与年龄相关性黄斑变性疾病的相关性

年龄相关性黄斑变性(age-related macular degeneration, ARMD)是一种多发于50岁以上人群的慢性进展性疾病, 是发达国家老年人群的主要致盲性眼病,也是发展中国家老年人群不可逆视力损害的主要原因, ARMD包括地图状萎缩及脉络膜新生血管两类。由于其具体病因和发病机制尚不明确, 大多数学者认为这是一种多因素疾病。近年来Toll样受体3(Toll-like receptor 3,TLR3)与ARMD关系的研究成为热点,本文就近年来相关研究进展做一综述。     

玻璃体腔内注射Bevacizumab治疗年龄相关性黄斑变性视野改变

目的 观察玻璃体腔内注射Bevacizumab(Avastin)治疗湿性年龄相关性黄斑变性(ARMD)术后各时间段的视野变化情况.方法 采用单中心随机临床研究方法.收集经间接眼底镜、荧光素眼底血管造影(FFA)以及光学相干断层扫描(OCT)检查确诊存在黄斑中心凹下脉络膜新生血管(CNV)的ARMD患者13例(15只眼),患眼最佳矫正视力均>0.1.患眼行Bevacizumab玻璃体腔内注射1.25mg(0.05ml),注射次数为6次,间隔6周至3个月,治疗后随访3～12个月,记录并分析术前及术后6周,3月,6月,12月的平均视觉敏感度(mean visual sensitivity,MS),平均缺损(mean defect,MD),缺损变异度(lose variance,Lv)的变化.结果 以0周注射为基准,第24周及48周MS值与注射前MS值相比有显著性差异(t值分别为2.91、3.69,P值均<0.05));第48周MD值与注射前MD值(7.97±3.97)dB差异有统计学意义(t值为1.35,P<0.05);各组LV值与注射前LV值比较差异无统计学意义.结论 多次玻璃体腔内注射Bevacizumab有利于改善湿性ARMD患者黄斑区视功能,主要体现在对视网膜平均敏感度以及平均缺损的改善上;重复4-6次注射后绝大多数湿性ARMD患者的视功能得到改善.     

玻璃体腔内注射Bevacizumab治疗年龄相关性黄斑变性视野改变

目的 观察玻璃体腔内注射Bevacizumab(Avastin)治疗湿性年龄相关性黄斑变性(ARMD)术后各时间段的视野变化情况.方法 采用单中心随机临床研究方法.收集经间接眼底镜、荧光素眼底血管造影(FFA)以及光学相干断层扫描(OCT)检查确诊存在黄斑中心凹下脉络膜新生血管(CNV)的ARMD患者13例(15只眼),患眼最佳矫正视力均>0.1.患眼行Bevacizumab玻璃体腔内注射1.25mg(0.05ml),注射次数为6次,间隔6周至3个月,治疗后随访3～12个月,记录并分析术前及术后6周,3月,6月,12月的平均视觉敏感度(mean visual sensitivity,MS),平均缺损(mean defect,MD),缺损变异度(lose variance,Lv)的变化.结果 以0周注射为基准,第24周及48周MS值与注射前MS值相比有显著性差异(t值分别为2.91、3.69,P值均<0.05));第48周MD值与注射前MD值(7.97±3.97)dB差异有统计学意义(t值为1.35,P<0.05);各组LV值与注射前LV值比较差异无统计学意义.结论 多次玻璃体腔内注射Bevacizumab有利于改善湿性ARMD患者黄斑区视功能,主要体现在对视网膜平均敏感度以及平均缺损的改善上;重复4-6次注射后绝大多数湿性ARMD患者的视功能得到改善.     

玻璃体腔内注射Bevacizumab治疗年龄相关性黄斑变性视野改变

目的 观察玻璃体腔内注射Bevacizumab(Avastin)治疗湿性年龄相关性黄斑变性(ARMD)术后各时间段的视野变化情况.方法 采用单中心随机临床研究方法.收集经间接眼底镜、荧光素眼底血管造影(FFA)以及光学相干断层扫描(OCT)检查确诊存在黄斑中心凹下脉络膜新生血管(CNV)的ARMD患者13例(15只眼),患眼最佳矫正视力均>0.1.患眼行Bevacizumab玻璃体腔内注射1.25mg(0.05ml),注射次数为6次,间隔6周至3个月,治疗后随访3～12个月,记录并分析术前及术后6周,3月,6月,12月的平均视觉敏感度(mean visual sensitivity,MS),平均缺损(mean defect,MD),缺损变异度(lose variance,Lv)的变化.结果 以0周注射为基准,第24周及48周MS值与注射前MS值相比有显著性差异(t值分别为2.91、3.69,P值均<0.05));第48周MD值与注射前MD值(7.97±3.97)dB差异有统计学意义(t值为1.35,P<0.05);各组LV值与注射前LV值比较差异无统计学意义.结论 多次玻璃体腔内注射Bevacizumab有利于改善湿性ARMD患者黄斑区视功能,主要体现在对视网膜平均敏感度以及平均缺损的改善上;重复4-6次注射后绝大多数湿性ARMD患者的视功能得到改善.     

Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration

PURPOSE: To evaluate the safety and efficacy of intravitreal bevacizumab (Avastin, Genentech Inc.) for the treatment of neovascular age-related macular degeneration (ARMD). METHODS: A retrospective review was performed on consented patients with neovascular ARMD receiving intravitreal bevacizumab therapy. All patients received intravitreal bevacizumab at baseline with additional monthly injections given at the discretion of the treating physician. At each visit, a routine Snellen visual acuity assessment was performed followed by an ophthalmic examination and optical coherence tomography (OCT) imaging. RESULTS: Fifty-three eyes of 50 patients received an intravitreal bevacizumab injection between May and August 2005. Including the month 3 visit, the average number of injections was 2.3 out of a maximum of 4 injections. No serious drug-related ocular or systemic adverse events were identified. Improvements in visual acuity and central retinal thickness measurements were evident by week 1 and continued through month 3. At month 3, the mean visual acuity improved from 20/160 to 20/125 (P < 0.001) and the mean central retinal thickness decreased by 99.6 microm (P < 0.001). CONCLUSION: Off-label intravitreal bevacizumab therapy for neovascular ARMD was well tolerated over 3 months with improvements in visual acuity and OCT central retinal thickness measurements. While the long-term safety and efficacy of intravitreal bevacizumab remain unknown, these short-term results suggest that intravitreal bevacizumab may be the most cost effective therapy for the treatment of neovascular ARMD.     

Profile of patients presenting at a low vision clinic in a developing country

ABSTRACT: BACKGROUND: Low vision is an important public health problem;however, very few low vision clinics are available to address the needs of low vision patientsin most developing countries. The purpose of this study was to describe the characteristics of patients attending the low vision clinic of a Nigerian tertiary hospital. METHODS: This was a prospective cross sectional study of all new patients seen at the low vision clinic over a 36 month period. Patients were administered with a structured questionnaire, and were examined and tested with low vision devices by the attending low vision specialist. Information on the demographic and clinical characteristics of the patients was recorded. RESULTS: A total of 193 new patients seen during the period were studied. The mean age was 41.4 years, and their ages ranged between 6 and 90 years with a male to female ratio of 1.9:1. Majority (58%) were aged below 50 years, 23.3% were children ([less than or equal to]15 years), while 21.8% were elderly patients ([greater than or equal to]65 years). The commonest cause of low vision was retinitis pigmentosa (16.6%); 14.5% had age related macular degeneration (ARMD); 9.8% had albinism; while only 1% had diabetic retinopathy. ARMD(45.2%) was the commonest cause in the elderly patients, while albinism (24.4%) and optic atrophy (24.4%) were the commonest in children. CONCLUSION: The demographic and clinical characteristics of low vision patients seen in this clinicare similar to that of patients in other developing countries, but different from those in developed countries. Elderly patients and females may be under-utilising low vision services. There is a need for further research into the determinants of low vision service utilisation in developing countries. This would further aid the planning and delivery of services to low vision patients in these countries.     

干性年龄相关性黄斑变性药物治疗研究进展

年龄相关性黄斑变性(ARMD)是全球范围内引起不可逆性视觉损伤的主要原因之一,且随着人口老龄化的加剧,患者数量逐渐增多,其中约90%为干性ARMD。干性ARMD缺乏有效的治疗措施,近年来成为了研究热点,其中药物治疗是主要的治疗方式之一。目前针对氧化损伤、炎症、血流障碍等ARMD致病因素,广泛开展了针对性的药物治疗,部分药物已被证实可减缓ARMD进展。本文总结了干性ARMD的药物治疗手段,包括抗氧化药物、补体类生物制剂、非甾体抗炎药和免疫抑制剂、血管扩张剂、神经保护药物及中药,对其作用机制及近年开展的临床研究进行综述,以期为干性ARMD的治疗与新药物的研发提供参考。     

干性年龄相关性黄斑变性现代医药与中医药研究新进展

年龄相关性黄斑变性(ARMD)是中老年人不可逆性视力损害的一种主要原因,严重影响个人生活质量并加重社会卫生经济负担。晚期ARMD在临床上有两种表现类型,即干性ARMD(dARMD)和湿性ARMD(nARMD)。nARMD以抗血管内皮生长因子作为一线药物已取得显著疗效,而dARMD尚无确切的治疗方法。本文就dARMD在临床试验中取得显著进展、可望上市的潜在药物、生物疗法和中医中药进行综述,包括抗炎药(强力霉素和FHTR2163)、抗氧化药(利舒尼布和依来米普瑞肽)、补体抑制剂(APL-2和滋目若)、视觉周期调节剂(ALK-001)、神经保护剂(溴莫尼定)、干细胞移植(MA09-hRPE和BMMF)、基因疗法(HMR59)和中医中药(藏红花、姜黄素、槲皮素和白藜芦醇)等。这些药物临床试验疗效显著,应用前景广阔,为ARMD改善与治疗带来巨大希望。     

Treatment of neovascular age-related macular degeneration with antiangiogenic drugs

Age-related macular degeneration (ARMD) remains a leading cause of blindness in the western world. Several clinical forms of the disease are recognized, whereas choroidal neovascularization (CNV) represents an important manifestation suitable for treatment. The treatment of CNV has been a major focus of research in the past decades, and the first evidence-based established therapy was laser photocoagulation, which reduces the risk of visual loss in extrafoveal lesions. In the late 90's photodynamic therapy has been established as an efficient method for the treatment of predominantly classic and occult CNV. Additional therapies such as macular translocation, submacular surgery, and indocyanine-mediated prothrombosis are currently under investigation in large-scale clinical trials. Molecular biology has recently provided a better comprehension of the pathogenesis of ARMD, and vascular endothelial growth factor (VEGF) was recognized as key mediator in the angiogenesis of CNV-formation. Therefore, the pharmacological approach rose as a key research area to treat CNV. The first FDA-approved agent for CNV-therapy is aptamer pegaptanib sodium (Macugen), which inactivates the key angiogenic isoform VEGF165. Additional VEGF-blockers such as ranibizumab RhuFab V2 (Lucentis) and bevacizumab (Avastin) are under evaluation in major clinical studies. Impressive results of intravitreal bevacizumab were released recently. Moreover, the steroid-derived anecortave acetate as well as the corticosteroid triamcinolone acetate have been proposed as methods for treatment of wet-ARMD. This paper presents the rationale and principles of the pharmacologic antiangiogenic therapy for CNV in ARMD.     

Age-related macular degeneration: the costs to society and the patient

PURPOSE OF REVIEW: The current literature was reviewed to assess the patient and societal costs associated with age-related macular degeneration (ARMD). RECENT FINDINGS: An increasing number of studies discuss the growing direct ophthalmologic, direct nonophthalmologic, and indirect costs associated with ARMD. Most reports, however, focus on only one of these aspects. The prevalence of this debilitating disease will increase as life expectancy increases. SUMMARY: ARMD continues to be a major public health problem in developed countries. The treatment and management of exudative ARMD are changing dramatically. These therapies will likely become a more significant portion of the overall healthcare burden of ARMD. To date, no comprehensive study exists that attempts to calculate the total cost of ARMD.     

现阶段治疗干性年龄相关性黄斑变性临床试验的总结与分析

年龄相关性黄斑变性(ARMD)是老年人不可逆性盲的主要原因之一。抗血管内皮生长因子(VEGF)药物已经成为新生血管性ARMD的一线治疗方法,极大地改变了其预后,但干性ARMD还是缺乏有效的治疗手段,以预防为主,目前几种临床治疗方法正在探索中,包括抗氧化治疗、补体治疗、神经保护治疗、基因治疗等。文章主要是对现有的治疗干性ARMD的临床试验及其进展进行归纳,以提供治疗干性ARMD的未来前景。一些临床试验已经得出了治疗干性ARMD有希望的结论,相信在不久的将来,会有越来越多的临床试验取得成功,为干性ARMD患者提供更有效的治疗方法。     

新生血管性年龄相关性黄斑变性治疗进展

年龄相关性黄斑变性是西方国家65岁以上人群视力损害和视力丧失的重要原因,是目前我国第三大致盲性眼病,主要影响中心视力。血管内皮生长因子在新生血管性年龄相关性黄斑变性的发病机制中起着重要的作用,目前抗血管内皮生长因子治疗已成为临床一线治疗方法。但仍有一部分患者需反复注射或不应答,因此需探索新的治疗方式进一步完善当前治疗,为今后新生血管性年龄相关性黄斑变性的治疗提供新思路。     

Intravitreal use of bevacizumab (Avastin) for choroidal neovascularization due to ARMD: a preliminary multifocal-ERG and OCT study

Purpose To evaluate by MFERG and OCT the macular function before and after intravitreal use of bevacizumab (Avastin) in eyes suffering from CNV due to ARMD. Methods Eighteen eyes with subfoveal CNV due to ARMD were studied before and after intravitreal use of bevacizumab with MFERG and OCT. The post treatment follow up was three months. Results Before treatment, OCT shows an increase of the retinal thickening of the fovea and the electrical response densities in the fovea and parafovea were decreased in all patients. Three months after treatment, OCT showed a real resolution of the subretinal fluid. The electrical responses in the fovea and parafovea remained the same or slightly improved in some cases. The intraocular pressure remained normal and no inflammation was observed. Conclusion The intravitreal use of bevacizumab may provide anatomical correlates that support the concept of disease amelioration but the functional improvement of the macula three months after treatment is not obvious. However the method is promising and needs further evaluation.     

Vitreous hemorrhage complicating age-related macular degeneration. Apropos of 18 cases

Vitreous hemorrhage as a complication of Age-Related Macular Degeneration (ARMD) is not a frequent event: 19 cases (out of 18 patients) are reported, corresponding to 0.6% of the patients with ARMD seen in the Department of Ophthalmology of Créteil between January 1st, 1979 and December 31, 1986. The relation between ARMD and vitreous hemorrhage was easy to establish on fundus examination after the resorption of the hemorrhage. However, during the acute hemorrhagic phase, the diagnosis was helped by the other eye fundus examination: this second eye presented with ARMD lesions in 15 out of 18 cases (78.9%). The most challenging differential diagnosis was the choroidal melanoma, when a subretinal hematoma hindered all underlying structures. Vitreous hemorrhages originated generally from well developed subretinal new vessels (17 cases out of 19) arising from the choroid. A retinal pigment epithelium tear, spontaneous or secondary to photocoagulation, was suspected to be the cause of the vitreous hemorrhage in one eye. Finally drugs (3 cases) and systemic diseases (6 cases) seemed to play a role. Visual prognosis is poor in most cases, as the result of the destruction of the macular photoreceptors (six eyes only retained a visual acuity equal or better than 20/400). Laser photocoagulation of the subretinal new vessels was possible for 5 eyes and allowed stabilisation of visual acuity in 2 eyes and improvement in one eye. Vitreous hemorrhage cleared in 16 out of 19 during the follow-up period and vitrectomy was therefore not performed in our series and not indicated at early stages.     

玻璃体腔注射bevacizumab治疗年龄相关性黄斑变性的初步临床观察

目的初步探讨玻璃体腔内注射bevacizumab（Avastin）治疗湿性年龄相关性黄斑变性（ARMD）的临床效果。方法采用单中心非随机对照临床研究方法。收集经荧光素眼底血管造影检查（FFA）、相干光断层成像术（OCT）确诊存在黄斑中心凹下脉络膜新生血管（CNV）的ARMD患者5例,患眼最佳矫正视力均〈0．1,无全身和局部手术禁忌证。患眼行bevacizumab玻璃体腔内注射术,用量为1．5mg（0．06ml）,记录手术前、后患眼的视力、眼压、FFA和OCT的检查结果。术后随访时间4～6个月。结果全部患者均未出现眼内和全身不良反应。1例患者术后第3天出现一过性眼压升高,局部给予降眼压药物治疗后症状得到控制。1例患者术后1周视力由0．1上升至0．4;4例患者术后2个月视力提高1—6行,其中3例于术后4—6个月时视力保持稳定,1例视力下降。3例患者术后1个月黄斑水肿明显改善,黄斑中心凹视网膜厚度较术前减少5．9％～41．4％,3例患者FFA显示CNV渗漏较术前减轻。结论玻璃体腔内注射bevacizumab治疗湿性ARMD安全,副作用少,可改善患者的视功能,减轻黄斑水肿,减少CNV渗漏,有望成为药物治疗ARMD的新方法,但尚需进行多中心大样本临床随机对照研究。     

Further support for the common variants in complement factor H (Y402H) and LOC387715 (A69S) genes as major risk factors for the exudative age-related macular degeneration

In developed countries, age-related macular degeneration (ARMD) is a common cause of blindness in the elderly. It is a clinically complex and genetically heterogeneous disorder. The etiology of the disorder may involve interactions between genetic and environmental factors. Recently it has been reported that a polymorphism in the complement factor H (CFH) and LOC387715 gene may determine the susceptibility of individuals to ARMD. In order to replicate and to determine the frequency of this polymorphism in ARMD patients, we have analyzed two unrelated families having exudative ARMD. Our analysis has identified the same common polymorphism (Y402H) in the CFH gene in one family and the A69S polymorphism in the LOC387715 gene in the second family. These results further support the notion that CFH and LOC387715 genes are the major risk factors for ARMD.     

Changes of serum VEGF concentration after intravitreal injection of Avastin in treatment of diabetic retinopathy

Purpose. Avastin (bevacizumab) intravitreal injections are widely used for treatment of diabetic retinopathy. The aim of our study was to analyze effect of 1.25 mg of intravitreal Avastin on serum concentration of vascular endothelial growth factor (VEGF) in diabetic patients. Methods. Participants were 10 diabetic patients on insulin therapy, without any other eye or systemic disease, and no kidney disfunction. Both eyes of diabetic patients were injected simultaneously with 1.25 mg of intravitreal Avastin, as a first step in treatment of nonproliferative diabetic retinopathy with clinically significant macular edema (4 patients), and of proliferative diabetic retinopathy (6 patients). Fluorescein angiography was performed prior to and laser therapy followed 1 month after Avastin treatment. VEGF concentration in patients serum was measured by ELISA technique: on the day of the Avastin administration, and 1, 7, and 28 days after intravitreal injection. Results. In all analyzed participants, 24 hours after Avastin treatment, serum levels of VEGF were lower then basal (preinjection value). Maximal reduction of serum VEGF was noted on the 7th postoperative day. Twenty-eight days after, VEGF level in serum was raised, without completely reaching basal preoperative concentrations in most patients. Conclusions. Intravitreal injections of anti-VEGF drugs have an effect on decreasing systemic VEGF values. Rhythm of changes in serum VEGF concentrations and lowest detected concentration on the seventh postinjection day are according to pharmacokinetics of Avastin in serum and vitreous, reported by similar studies. The small number of patients involved in this pilot study implicates the need for further studies.     

Appearance of age‐related macular degeneration in vitrectomized and nonvitrectomized eyes: an intraindividual case study

Purpose: This study analyses the consequences of vitreoretinal traction on the macula and in particular the impact of a vitrectomy on the development of the age‐related macular degeneration (ARMD). Methods: In this retrospective case study, 42 eyes of 21 subjects were examined. The vitreous of one eye must have been removed by vitrectomy at least 8 years ago. At that point in time, the patients had to be at least 50 years old, with a healthy vitreous body of the other eye and a healthy macula in both eyes. Both eyes were examined using an optical coherence tomography (OCT) scan, B‐scan ultrasound, a binocular slit‐lamp funduscopy and a fluorescence angiography (FAG) to evaluate the potential development stage of an ARMD and the vitreous status. Results: In the follow‐up examination, the patients had an average age of 73.6 years. In 0 of 21 vitrectomized eyes (0%), there were signs for an early ARMD. In 5 of 21 nonvitrectomized eyes (23.8%), we found ARMD‐like changes in the angiography and slit‐lamp examinations. Of these 21 eyes, five eyes presented persistent attachment of the posterior vitreous cortex to the macula, while 16 eyes showed complete posterior vitreous detachment. All five eyes (100%) with premonitory signs of an ARMD showed persistent attachment of the posterior vitreous to the macula. Conclusion: We demonstrated a positive relationship between a persistent attachment of the posterior vitreous cortex to the macula and early signs of ARMD. Although the precise mechanism of this relationship remains unclear, the role of chronic low‐grade inflammation, chronic oxidative and mechanical stress and an increase in VEGF is discussed. Persistent vitreous attachment is likely to be another risk factor for ARMD.     

抗VEGF药物在湿性年龄相关性黄斑变性中的应用进展

年龄相关性黄斑变性(ARMD)是导致老年人不可逆失明的主要原因之一,ARMD致失明患者中,以脉络膜新生血管(CNV)为特征的湿性ARMD比例达到90%。随着我国老年人口比例的不断上升,湿性ARMD已经成为一个日益严重的社会医学问题。目前,针对湿性ARMD的治疗方案主要是抗血管内皮生长因子(VEGF)药物的应用,这类药物抑制了CNV的发展,提高了患者视力,改善了预后,降低了致盲率。但是在治疗过程中的无反应、长期用药后的维持和用药后的耐受、不良反应以及用药的经济效益也是我们需要关注的。本文就近年来临床用于治疗湿性ARMD的药物进行综述。     

Nutrition et dégénérescences maculaires liées à l'âge

The pathogenesis of age-related macular degeneration (ARMD) involves nutritional factors related to the oxidative stress. Antioxidant micronutrients, anti-free-radicals and micronutrients that protect from blue light play a role in disease prevention. These nutritional factors are closely related to environmental risk factors such as smoking and chronic blue light exposure. Although experimental and epidemiological data are concordant and coherent, the protective role of these micronutrients is not clearly established and the effective dose devoid of adverse effects remains to be determined. Besides, interventional studies on omega-3 long-chain polyunsaturated fatty acids (LCPFA) supplements constitute a significant advance in terms of primary care prevention. In practice, as primary disease prevention, omega-3 LCPFA supplements may be considered in subjects with a risk for ARMD, while a cocktail of antioxidant and blue-light-protective micronutrients should be considered for patients with grade 3 and grade 4 ARMD, or, as secondary prevention, for subjects with an uncontrolled nutritional status. Of course, such supplements are compatible with simple dietary measures. Their interest might be enhanced by an improved formulation and a dose-optimization of the supplements currently used. Further research and clinical studies remain necessary to definitely validate these formulations and consider them true drugs.