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。     

Treatment of dry age-related macular degeneration: A review

Age-related macular degeneration is a global disease with a significant societal impact. The advent of anti-vascular endothelial growth factor therapy (anti-VEGF) has revolutionised the treatment of neovascular age-related macular degeneration (nAMD). Dry age-related macular degeneration (dAMD) is being investigated for possible therapeutic options. The therapeutic categories undergoing clinical trials include complement pathway inhibitors, visual cycle modulators, reduction of toxic byproducts, antioxidative therapy, neuroprotective agents, laser therapy, surgical options, gene therapy, stem cell therapy, and miscellaneous treatments. Two intravitreal anti-complement factors (pegcetacoplan and avacincaptad pegol) have recently shown phase 3 clinical trial evidence of a reduction in the growth of geographic atrophy. In this review, we provide an update on treatment options currently undergoing clinical research trials for the management of dAMD and preventing the progression of Geographic Atrophy (GA).     

年龄相关性黄斑变性的治疗研究进展

年龄相关性黄斑变性(age-related macular degeneration,AMD)又称为老年性黄斑变性,常伴有进行性视力损害,严重影响老年人的生存质量,是全世界第三位不可逆性致盲眼病。虽然AMD目前尚未成为我国人群致盲的首要原因,但是随着社会的老龄化,AMD在我国的发病率也逐渐升高。近年来,国内外学者对AMD进行了大量深入的研究,对本病有了更进一步的认识,现就AMD目前有关的治疗方法及其进展做一综述。     

玻璃体腔内注射Bevacizumab治疗湿性年龄相关性黄斑变性的临床应用

湿性年龄相关性黄斑变性(age-related macular degeneration,AMD)是以黄斑区出现脉络膜新生血管膜(choroidal neovascularization,CNV)为特点,血管内皮生长因子(vascular endothelial growth factor,VEGF)是目前已知促新生血管形成最主要的刺激因子,VEGF抑制剂通过拮抗作用,抑制血管生成、降低血管通透性,促进CNV渗液的吸收.Bevacizumab虽然存在药物标识外使用(off-label)问题,它对湿性AMD仍以相对好的短期治疗效果和低廉的治疗成本在国际眼科界被广泛应用.玻璃体腔内1个月注射1次Bevacizumab(1.25 mg),连续注射3次的方案优于注射1次后再根据病情再次注射的方案.治疗后湿性AMD患者眼底解剖结构和视力均有明显改善.     

潜在抗氧化剂在年龄相关性黄斑变性中应用的研究进展

年龄相关性黄斑变性(AMD)是导致老年人视力严重损害甚至丧失的主要原因。随年龄增长,氧化应激逐渐累积,这是导致AMD发生发展过程中视网膜损伤的关键因素。目前,抗氧化剂已成为AMD防治的重要临床用药,但部分药物对患者视力的改善效果并不明显,且存在一定的副作用。为进一步改善AMD防治效果,研发新的单用、联用药物并制定靶向多机制治疗方案已成为新的研究热点。近年来,一些新型抗氧化剂已进入实验阶段,并在多种视网膜氧化应激模型中表现出一定效果。本文总结了近年来的研究成果,探讨了诸多潜在抗氧化剂在动物或细胞实验中的作用和机制,对临床进一步筛选AMD的防治用药具有重要意义。     

年龄相关性黄斑变性的治疗进展

年龄相关性黄斑变性（ａｇｅ-ｒｅｌａｔｅｄｍａｃｕｌａｒｄｅｇｅｎｅｒａｔｉｏｎ,ＡＭＤ）是致盲的重要疾病,其发生机制尚不明确,通过修正吸烟这一重要环境危险因素及补充抗氧化剂可能干预ＡＭＤ的发生发展。补体抑制、神经保护和视觉周期抑制等干预策略是近年来治疗干性ＡＭＤ的重要研究方向。目前对于湿性ＡＭＤ的治疗已取得重大进展:通过玻璃体内注射抗血管内皮生长因子药物疗效显著,但频繁注射需承担较大手术风险,且受患者经济水平等因素限制,联合治疗似乎可以减少再治疗次数。抗色素上皮衍生因子联合抗血管内皮生长因子治疗及基因治疗可能给未来ＡＭＤ的治疗提供一个长效治疗的新方法。     

光动力疗法治疗老年黄斑变性临床初步观察

目的　观察应用光动力疗法 (photodynam ic therapy,PDT )单次治疗渗出型年龄相关性黄斑变性 (age- related m acu-lar degeneration,A MD )并发脉络膜新生血管 (choroidal neovascularization,CN V )的近期治疗效果。方法　以眼底检查、视力、眼底荧光血管造影 (FFA)、吲哚青绿脉络膜血管造影 (ICG)和光学相干断层成像技术 (O CT)等影像学检查为观察指标 ,总结PDT治疗 15例 16眼 A MD合并的典型 CNV后 1周和 1个月随访的短期治疗效果 ,从而评价 PDT治疗 CNV的安全性和短期治疗效果。结果　治疗后 1周和 1个月分别有 6眼和 10眼视力不同程度提高 ,1眼因新出血视力略有下降 ,无证据表明与治疗有关。 15例 16眼治疗后荧光渗漏均有不同程度的减弱或消退 ,其中 7例 8眼渗漏完全消退 ,1月后复查无复发 ;其余 8例8眼荧光渗漏明显减轻。全部 15例治疗过程中未发生任何不良反应 ;仅 3例治疗后主述有一过性轻度视力紊乱。结论　光动力疗法单次治疗渗出型年龄相关性黄斑部变性并发的脉络膜新生血管膜短期疗效满意、安全 ,对视力无损害。     

年龄相关性黄斑变性治疗新进展

年龄相关性黄斑变性是发达国家中老年人群主要致盲眼病,其患病率逐年上升。近年来其治疗方面取得很大进展。预防性治疗以抗氧化剂为代表,近来也出现了一些新的治疗方法,如他汀类药物等。抗CNV的治疗重心由激光治疗转为从转录及表达水平针对VEGF及其受体的治疗。联合治疗是研究CNV治疗新的发展方向,多项试验验证了PDT联合抗VEGF治疗的有效性。但是手术治疗CNV作为一项补充的治疗措施,其疗效需要更多的随机对照临床试验验证。     

老年性黄斑变性的研究进展

综述了老年性黄斑变性（AMD）近几年的研究现状,包括AMD的流行病学,病因学,病理机制和中西医治疗等。其中AMD的发病与年龄,人种,遗传史,吸烟,环境等因素有关;病理机制与视网膜色素上皮的代谢障碍和慢性非特异性炎症性病变有关;治疗方法主要有激光光凝,光动力学,手术,放射,基因,药物等。由于目前对AMD的治疗尚无确切疗法,应用中医药进行治疗是一个值得探索的方向。     

老年黄斑变性的治疗新进展

老年黄斑变性( age-related macular degeneration,AMD)是西方国家白种人不可逆性视力下降的首要原因。目前, AMD的治疗方法主要有抗血管内皮生长因子抗体( Anti-vascular endothelial growth factor,Anti-VEGF)的药物治疗、光动力学疗法( photodynamic therapy,PDT)、局部应用曲安奈德(triamcinolone acetonide,TA)及激光治疗(纳秒激光等)等。本文通过对比分析老年黄斑变性的不同治疗方法的作用原理、治疗效果、副作用、经济成本,为临床治疗提供依据。     

光动力疗法治疗脉络膜新生血管性疾病的初步临床观察

目的:观察使用维替泊芬光动力疗法(photodynamic thera-py,PDT)治疗年龄相关性黄斑变性(age-related maculardegeneration,AMD)、病理性近视和特发性脉络膜新生血管(choroidal neovascularization,CNV)等3种主要的CNV相关疾病的临床效果。方法:对96例(109眼)经临床确诊的上述CNV患者进行PDT治疗,随访1～24(平均9.4)mo。采用最佳矫正视力、荧光素血管造影、吲哚青绿血管造影、光学相干断层成像等指标,观察治疗前后患者的视功能、CNV病灶大小及渗漏情况、以及视网膜水肿变化等,评价PDT治疗CNV的疗效。结果:本组病例包括AMD42例(54眼),病理性近视17例(18眼),特发性CNV患者37例(37眼)。AMD、病理性近视和特发性CNV的平均治疗次数分别为1.2,1.5和1.2次;视力稳定和提高者各组分别为83.3%,83.3%和86.5%;CNV渗漏停止或减少者各组分别为90.7%,83.3%和89.2%:视网膜水肿减轻者各组分别为77.8%,88.9%和86.5%。除3例AMD患者出现眼部严重不良反应外,未发现其他严重不良反应。结论:PDT可有效地改善或稳定AMD、病理性近视和特发性CNV患者的视功能,控制病变进展,近期随访结果安全有效。     

年龄相关性黄斑变性的基因治疗

年龄相关性黄斑变性（AMD）是老年人主要的致盲眼病之一,湿性型AMD危害较大,主要表现为脉络膜新生血管（CNV）的形成,目前尚无理想有效的治疗方法。随着分子生物学技术的发展,基因治疗为AMD的治疗提供了新思路。现已发现许多启动和抑制CNV的基因,以及可能导致AMD发生的基因位点,其中补体因子H（CFH）被认为是引发AMD的关键基因。就目前AMD基因治疗的载体、靶基因的选择以及引发AMD的关键基因进行综述。     

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。     

Use of fluorescein and indocyanine green angiography in polypoidal choroidal vasculopathy patients following photodynamic therapy

Background: Exudative age-related macular degeneration (AMD) is a sight-threatening event in many elderly people. Some patients have a much better outcome in visual acuity (VA) than others after treatment with photodynamic therapy (PDT) with verteporfin. The combination of fluorescein angiography (FA) and indocyanine green (ICG) angiography using the Heidelberg Retina Angiograph II (HRA 2) should make a delineation of distinct pattern(s) possible in order to better select and assess therapy.Methods: This is a retrospective, case-control, single-centre study. We identified a total of 168 eyes of 168 patients from July 2003 to June 2006, including 30 eyes of 30 patients with better visual outcome, defined in this study as VA ≤0.48 logMAR (≥20/60 Snellen chart) at the end of the study. Best-corrected VA, maximal central retinal thickness as measured by optical coherence tomography, and results of the FA/ICG angiography using the HRA 2 were analyzed. In this article, we discuss patients with polypoidal choroidal vasculopathy (PCV) and their characteristics.Results: The average follow-up time was 15.3 months (range 4–28 months). Seventeen (57%) of the 30 patients with better visual outcome had PCV. All patients in the group with better visual outcome needed fewer PDT treatments compared with our control group of patients with an exudative AMD.Interpretation: Simultaneous FA/ICG angiography using the HRA 2 allowed delineation of a subgroup of patients with PCV who showed a better visual outcome compared with those with other types of exudative AMD, after treatment with PDT.     

Lucentis治疗黄斑脉络膜新生血管1年的临床疗效观察

目的 采用1+ PRN的方案治疗年龄相关性黄斑变性(age-related macular degeneration,AMD)及高度近视黄斑脉络膜新生血管(choroidal neovascularization,CNV),观察其1 a疗效.方法 收集2012年7月至2014年4月在我院眼科就诊,确诊为黄斑区CNV(继发于AMD或高度近视者)并接受单一的玻璃体内注射Lucentis(单次剂量0.5 mg/0.05 mL)的73例(79眼;其中AMD患者38眼,高度近视黄斑CNV患者41眼)患者的临床资料.记录治疗后1d、1周及1 a内每月的最佳矫正视力(best corrected visual acuity,BCVA)、黄斑中心视网膜厚度(central retina thickness,CRT)以及1 a后地图状萎缩进展情况.结果 治疗后不同时间点AMD与高度近视患者的平均BCVA均较治疗前提高,差异均有统计学意义(均为P＜0.05),其中治疗后1周～3个月提高幅度最明显,治疗后3个月～1 a基本保持平稳.CRT变化情况与BCVA一致.1 a观察终点时,所有患者中治疗眼与非治疗眼地图状萎缩的发展并无明显差异.随访期内,10眼结膜下出血,1眼虹膜色素脱失,1眼轻度视网膜劈裂,未发现眼压升高、视网膜脱离、眼内炎等其他局部并发症及全身不良反应.结论 采用1+ PRN治疗方案治疗AMD与高度近视黄斑CNV在1 a期间是安全有效的,注射次数较少的情况下对患者地图状萎缩进展影响不大.     

光动力学疗法治疗AMD后OCT检查的特征性改变

目的：通过前瞻性观察PDT治疗湿性年龄相关性黄斑变性（aged-related macular degeneration,AMD）前后不同随访时间点光学相干断层成像（optical coherence tomography, OCT）的特征性改变,旨在更好地反馈PDT治疗后黄斑区结构的变化过程。方法：将在本院接受PDT治疗的26例30眼湿性AMD患者纳入本研究。维速达尔用量根据厂家推荐方法计算。治疗前后均行FFA,ICG,OCT及最佳矫正视力等相关临床检查,术后随访日期为术后2wk; 1,2,3mo。傅立叶OCT扫描以标准五线结合六线扫描,覆盖病变的关键部位并保持前后扫描位置的一致性。重点观察黄斑中心凹层间厚度、外层高反射带高度、囊肿（包括视网膜下积液和视网膜内积液）的总面积。分析这些变化与随访时间的依赖关系。统计分析使用SPSS 13.0软件。结果：至治疗后3mo,PDT治疗后22眼（73%）视力提高两行以上,3眼视力无明显改变,3眼视力下降,2例患者因故失访。视力提高的22眼治疗前平均黄斑厚度为 722.5±55.6μm,治疗后2wk,平均黄斑层间厚度为708.3±45.3μm,1mo 为584.4±49.3μm,2mo为430.7±50.2μm,3mo为 180.6±36.3μm。治疗前和治疗后外层高反射带厚度分别为302.3±50.2,277.5±42.3,202.7±40.1,180.6±35.7,100.8±22.9μm,囊肿的总面积为0.34±0.12,0.25±0.07,0.10±0.05,0.08±0.04,0.05±0.01mm2。结论：AMD患者在PDT治疗后1mo黄斑区视网膜下液有显著吸收,视网膜水肿显著吸收,黄斑中心凹层间厚度、外层高反射厚度也有明显变薄倾向。     

干性年龄相关性黄斑变性患者视网膜色素上皮细胞损伤机制

年龄相关性黄斑变性(age-related macular degeneration,AMD)是中老年人视力障碍的重要原因之一。AMD分为2型:萎缩型(干性)和渗出型(湿性)。本文从光照损伤、脂褐素积累、氧化损伤、内质网应激4个方面,综述了干性AMD研究中基于视网膜色素上皮细胞损伤的相关研究进展,为进一步探索其发病机制提供依据和方向。     

老年黄斑变性外周血中视网膜抗体的研究

目的 探索老年黄斑变性（ＡＭＤ）的免疫发病机理。方法 运用ＳＤＳ－ＰＡＧＥ电泳、免疫印迹技术检测老年黄斑变性患者外周血中视网膜抗体;运用免疫组化法组织定位。结果 老年黄斑变性患者外周血中存在显著高于正常对照组的视网膜抗体,其相应抗原相对分子质量为２７０００～３５０００,４３０００～５００００,５６０００～６７０００,８００００～９００００,抗原定位在视网膜光感受器外节和神经元的胞核。结论 自身免疫反应是老年黄斑变性发生、发展的一个重要因素。     

Combination of ranibizumab with photodynamic therapy vs ranibizumab monotherapy in the treatment of age-related macular degeneration:a systematic review and meta-analysis of randomized controlled trials

AIM:To compare the efficacy and safety of combination of ranibizumab with photodynamic therapy (PDT) vs ranibizumab monotherapy in the treatment of age-related macular degeneration (AMD).METHODS:The Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Pubmed, and Embase were searched. There were no language or data restrictions in the search for trials. Only randomized controlled trials (RCTs) were included. Methodological quality of the literatures was evaluated according to the Jadad Score. RevMan 5.2.6 software was used to do the meta-analysis.RESULTS:Seven studies were included in our systematic review, among which four of them were included in quantitative analysis. The result shows that the ranibizumab monotherapy group had a better mean best corrected visual acuity (BCVA) change vs baseline at month 12 compared with that of the combination treatment group, and the statistical difference was significant (WMD, -2.61; 95% CI, -5.08 to -0.13; P=0.04). However, after the removal of one study, the difference between the two groups showed no significant difference (WMD, -2.29; 95% CI, -4.81 to 0.23; P=0.07). Meanwhile, no significant central retinal thickness (CRT) reduction was found in the combination treatment group and the ranibizumab monotherapy group at 12 months follow-up. Nevertheless, the combination group tended to have a greater reduction in CRT (WMD, -4.13μm; 95%CI, -25.88 to 17.63, P=0.71). The proportion of patients gaining more than 3 lines at month 12 in the ranibizumab group was higher than in the combination group and there was a significant difference (RR, 0.72; 95% CI, 0.54 to 0.95; P=0.02). Whereas there was no significant difference for the proportion of patients gaining more than 0 line at month 12 between the two groups (RR, 0.93; 95% CI, 0.76 to 1.15; P=0.52). The general tendency shows a reduction in ranibizumab retreatment number in the combination treatment group compared with the ranibizumab monotherapy group. As major adverse events, the differences in the number of eye pain, endophthalmitis, hypertension and arterial thromboembolic events were not significant between the two groups, and the incidence of serious adverse events in the two groups was very low.CONCLUSION:For the maintenance of vision, the comparison of the combination of ranibizumab with PDT vs ranibizumab monotherapy shows no apparent difference. Compared with the combination of ranibizumab and PDT, patients treated with ranibizumab monothearpy may gain more visual acuity (VA) improvement. The combination treatment group had a tendency to reduce the number of ranibizumab retreatment. Both the two treatment strategies were well tolerated.     

治疗湿性年龄相关性黄斑变性的抗VEGF药物研究进展

湿性年龄相关性黄斑变性( wet age-related macular degeneration,wet-AMD)是引起视力不可逆损伤的重要原因,目前公认的一线治疗方式为抗VEGF治疗,但有部分患者即使反复接受抗VEGF治疗,视力仍无法提高或稳定维持。为了进一步提高湿性AMD患者有效视力,衍生出了多种新的治疗方式,包括通过相同或不同的抗新生血管靶点发挥作用、联合治疗巩固提高抗VEGF的功能、改变或简化给药方式等,本文就治疗湿性AMD的抗VEGF药物研究进展做一简要综述。