光动力疗法联合玻璃体腔注药术治疗脉络膜新生血管的研究进展

脉络膜新生血管是很多眼底疾病视力下降甚至丧失的重要原因.近年来,以光动力疗法,抗新生血管药物使用为代表的治疗方法取得了较好的效果,能有效的封闭黄斑下脉络膜新生血管并稳定视力.     

光动力疗法在脉络膜新生血管治疗中的应用

光动力疗法(phtotodynamic therapy,PDT)是一种利用光化学反应特异性地阻塞新生血管而达到治疗目的的新技术.近年来对PDT治疗脉络膜新生血管进行了大量研究.本文就光动力疗法的原理、光敏剂种类以及它在脉络膜新生血管治疗上的一些进展作综述.     

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重要的致盲性疾病之一,其主要特点就是黄斑区玻璃膜疣,色素上皮萎缩和脉络膜新生血管形成伴随着中心视力受损.近年对脉络膜-Bruch's膜-色素上皮复合体的病理变化做了大量研究,针对脉络膜新生血管的一些治疗方法如PDT、TTT、对抗新生血管生成疗法,基因疗法也有新的突破.     

年龄相关性黄斑变性脉络膜新生血管的联合治疗

年龄相关性黄斑变性引起的脉络膜新生血管是中老年人群中心视力丧失的常见原因之一,其治疗已成为眼底病领域研究的热点.目前对脉络膜新生血管的治疗方法有多种,然而现有的任一种单一疗法都难以显著提高视力且复发率较高,不能满足患者需要.近年来,随着对脉络膜新生血管发病机制的深入研究,治疗手段逐渐趋于具不同治疗机制的方法联合应用,以求获得最大疗效并 最大可能减少治疗相关的并发症.     

脉络膜新生血管抑制剂最新研究进展

脉络膜新生血管是脉络膜血管病理性增生表现,易伴发出血及渗出,是致盲的主要因素之一.目前针对脉络膜新生血管的治疗成为了研究热点,并且在血管内皮生长因子及其受体抑制剂、内源性血管生成因子抑制剂、氧化还原和炎症反应相关因子抑制剂等研究上取得了一定进展,有关此病的中药治疗也取得相应成就.本文就脉络膜新生血管抑制剂最新研究进展展开综述.     

黄斑中心凹下脉络膜新生血管的光动力学治疗

光动力学疗法 (PDT)是由治疗肿瘤而发展起来的一种新的治疗新生血管的方法。近年来 ,应用于眼科领域治疗眼底脉络膜新生血管 ,在动物实验与临床研究方面都已取得一定的进展。本文介绍了PDT的作用机制 ,PDT的病理组织学改变 ,以及应用PDT治疗黄斑中心凹下脉络膜新生血管的临床研究及最新进展。     

光动力疗法治疗脉络膜新生血管性疾病后导致的脉络膜低灌注

脉络膜新生血管(CNV)是引起多种眼底疾病视力障碍的主要原因.目前临床上有多种治疗方法,如光动力疗法(PDT)、抗血管内皮生长因子(VEGF)疗法、经瞳孔温热疗法(TTT)等,但都不能彻底治愈CNV,需要重复多次治疗.其中,PDT能特异性封闭CNV,但可引起脉络膜低灌注.就PDT治疗后产生的脉络膜低灌注及其影响和应对措施进行综述,回顾PDT治疗后发生脉络膜低灌注的证据,与临床效果之间的关系,评估联合治疗的作用,讨论使用低照度光动力激光治疗减少低灌注的潜力.     

黄斑中心凹下脉络膜新生血管的光动力学治疗

光动力学疗法（PDT）是由治疗肿瘤而发展起来的一种新的治疗新生血管的方法。近年来，应用于眼科领域治疗眼底脉络膜新生血管，在动物实验与临床研究方面都已取得一定的进展。本介绍了PDT的作用机制，PDT的病理组织学改变，以及应用PDT治疗黄斑中心凹下脉络膜新生血管的临床研究及最新进展。     

光动力疗法在脉络膜新生血管治疗中的应用

光动力疗法(photodynamic therapy，PDT)是一种利用光化学反应特异性地阻塞新生血管而达到治疗目的的新技术。近年来对PDT治疗脉络膜新生血管进行了大量研究。本文就光动力疗法的原理、光敏剂种类以及它在脉络膜新生血管治疗上的一些进展作一综述。     

靶分子疗法在脉络膜新生血管治疗中的研究

脉络膜新生血管的发生与新生血管抑制因子和生长因子的失衡有关,近年开展的靶分子疗法是一种新的独特的治疗脉络膜新生血管的方法,包括抗血管内皮生长因子、抗脉络膜新生血管内皮细胞的单克隆抗体、组织蛋白酶抑制剂和色素上皮源性因子等。本文对这些研究的进展进行综述。     

Verteporfin therapy for subfoveal choroidal neovascularization in age-related macular degeneration: From clinical trials to clinical practice

People with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) are at high risk of central vision loss. Until verteporfin therapy became available, there was no safe and effective treatment for a large majority of these people. The phase III clinical trials of verteporfin therapy showed that treatment could safely reduce the risk of vision loss in the majority of patients presenting with either predominantly classic CNV or with occult with no classic CNV, and in selected patients with minimally classic CNV. The decision to treat patients with subfoveal CNV due to AMD using verteporfin therapy, requires an understanding of the outcomes of these clinical trials and of published guidelines. This review presents the key findings of the trials and outlines the factors that should be considered in clinical practice when deciding whether verteporfin therapy is indicated.     

Verteporfin therapy for subfoveal choroidal neovascularization in age-related macular degeneration: from clinical trials to clinical practice

People with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) are at high risk of central vision loss. Until verteporfin therapy became available, there was no safe and effective treatment for a large majority of these people. The phase III clinical trials of verteporfin therapy showed that treatment could safely reduce the risk of vision loss in the majority of patients presenting with either predominantly classic CNV or with occult with no classic CNV, and in selected patients with minimally classic CNV. The decision to treat patients with subfoveal CNV due to AMD using verteporfin therapy, requires an understanding of the outcomes of these clinical trials and of published guidelines. This review presents the key findings of the trials and outlines the factors that should be considered in clinical practice when deciding whether verteporfin therapy is indicated.     

Novel approach for management of age-related macular degeneration--antiangiogenic therapy and retinal regenerative therapy

Age-related macular degeneration (AMD) is a leading cause of legal blindness in developed countries. Even with the recent advent of several treatment options, treatment of exudative AMD, characterized by choroidal neovascularization (CNV), remains difficult. Thus, in this review article, we report on the investigation of novel approaches for the management of AMD, antiangiogenic therapy for CNV, and retinal regenerative therapy. Polyion complex(PIC) micelles have a range in size of several tens of nanometers formed through an electrostatic interaction, and accumulate in solid tumors through an enhanced permeability and retention(EPR) effect. In this study, we examined the distribution of the PIC micelles which encapsulate fluorescein isothiocyanate-labeled poly-L-lysine{FITC-P(Lys)} in experimental CNV in rats, to investigate whether PIC micelles can be used for the treatment of CNV. We demonstrated that PIC micelles accumulate in the CNV lesions and are retained in the lesions for as long as 168 hours after intravenous administration. These results raise the possibility that PIC micelles can be used for achieving an effective drug delivery system against CNV. Although photodynamic therapy (PDT) is a very promising treatment for AMD, most patients require repeated treatments. For effective PDT against AMD, the selective delivery of a photosensitizer to the CNV lesions and an effective photochemical reaction at the CNV site are necessary. The characteristic dendritic structure of the photosensitizer prevents aggregation of its core sensitizer, thereby inducing a highly effective photochemical reaction. We present an effective PDT for AMD employing a supramolecular nanomedical device, i.e., a novel dendritic photosensitizer encapsulated in a polymeric micelle formulation. With its highly selective accumulation in CNV lesions, this treatment resulted in a remarkably efficacious CNV occlusion with minimal unfavorable phototoxicity. Our results will provide a basis for an effective approach to PDT for AMD. Spatial control of gene transfection in the body is a core issue in the gene therapy for ocular diseases including AMD. Photochemical internalization (PCI) is a technology that effects light-induced delivery of DNA directly inside cells. PCI usually requires that a photosensitizer be added to the drug-delivery system to photochemically destabilize the endosomal membrane. We have developed a ternary complex composed of a core containing DNA packaged with cationic peptides and enveloped in the anionic dendrimer, phthalocyanine, which provides the photosensitizing action. Subconjunctival injection of the ternary complex followed by laser irradiation resulted in transgene expression only in the laser-irradiated site in rats. This PCI-mediated gene delivery system is potentially useful in gene therapy for ophthalmic diseases. Accumulation of lipofuscin is related to an increased risk of AMD. We report that a major lipofuscin component, A2E(N-retinyledin-N-retinylethanolamin), activates the retinoic acid receptor (RAR). In vivo experiments suggest that A2E accumulation results in the pro-angiogenic conversion of retinal pigment epithelial(RPE) cell phenotype. This physiological consequence of A2E accumulation may be related to a novel potential therapeutic target for CNV. To recover visual function damaged by AMD, retinal regenerative therapy is essential. We investigated whether subretinal transplantation of bone marrow mesenchymal stem cells(MSCs) promotes photoreceptor survival in a rat model of retinal degeneration. Morphological and functional studies in vivo, including histological analysis and electrophysiological studies, indicate that the subretinal transplantation of MSCs delays retinal degeneration and preserves retinal function. These results suggest that MSC is a useful cell source for cell-transplantation therapy for retinal degeneration. In order to elucidate the molecular mechanisms of development of the fovea, which is composed mainly of cone photoreceptors and is susceptible to injury from AMD, we performed a comparative gene expression analysis between the central and peripheral regions of the monkey retina using monkey (rhesus macaque) genome microarray chips. We then selected the clones which were expressed at significantly higher levels in the central region and confirmed their expression in the monkey retina by section in situ hybridization. This study sheds light on the mechanisms of foveal development and may lead to the development of regenerative medicine for cone photoreceptors.     

Clinical effects of photodynamic therapy with Verteporfin for age-related macular degeneration 1: three-month results

PURPOSE: To evaluate the 3-month effects after one-time photodynamic therapy (PDT) for subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (AMD). SUBJECTS AND METHODS: The subjects were 122 patients with subfoveal CNV due to AMD detected by fluorescein angiography (FA). FA, indocyanine-green angiography (IA), and the examination of visual acuity were done before and 3 months after PDT. The diameter of CNV in FA was compared, and ophthalmological examination before the treatment determined whether there were any factors associated with a reduction or suppression of CNV. RESULTS: 3 months after PDT, 89 eyes had a significant (p < 0.001) reduction of CNV (41 eyes had blockage of CNV). In case of polypoidal choroidal vasculopathy (PCV) detected by IA, CNV was significantly reduced compared with the effects of other types of therapy (p = 0.032). Moreover, CNV was blocked significantly when fibrin tissue was present on a part of CNV before treatment (p = 0.026). Visual acuity was maintained or improved in 96 eyes. CONCLUSION: One-time PDT was effective in reducing or suppressing CNV as confirmed by FA.     

光动力治疗年龄相关性黄斑变性的联合用药研究进展

年龄相关性黄斑变性(age-related macular degeneration,AMD)是目前老年人的主要致盲因素。近90%AMD患者的严重视力丧失是由脉络膜新生血管(choroidal neovascularization,CNV)所引起。维替泊芬(verteporfin)是目前唯一被批准用于光动力疗法(photodynamic therapy,PDT)治疗新生血管性AMD的光敏剂。本文综述了近年来维替泊芬和抗血管生成药物联合治疗新生血管性AMD的新进展,并探讨其治疗效果的差异和视力恢复情况。     

Early detection, diagnosis and management of choroidal neovascularization in age-related macular degeneration: the role of ophthalmologists

Choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) is a serious condition which, if unrecognized and untreated, can result in the rapid deterioration of vision. Early detection and prompt referral to a retina specialist may potentially reduce the high risk of severe vision loss. The majority of AMD patients with CNV who present to an ophthalmologist will have been referred by either a primary care physician or an optometrist. Following referral, ophthalmologists will confirm diagnosis and identify the location and composition of the CNV. This information will provide the basis for a decision on what treatment, if any, is indicated. Until last year, laser photocoagulation was the only clinically-proven treatment option for neovascular AMD in large-scale randomized clinical trials, although many patients were not eligible for this treatment. Verteporfin (Visudyne(TM)) therapy is a new treatment option that uses photodynamic therapy in patients with predominantly classic subfoveal CNV secondary to AMD. Retrospective analyses show that the introduction of verteporfin therapy is likely to increase the number of patients with neovascular AMD who can be treated. Early detection, prompt referral and treatment, together with appropriate use of low vision aids, will help to optimize patient outcomes and quality of life.     

经瞳孔温热疗法治疗年龄相关性黄斑变性

年龄相关性黄斑变性（AMD）是老年人致盲的常见原因。根据其临床表现可分为干性和湿性。湿性AMD以视网膜色素上皮（RPE）下有活跃的脉络膜新生血管（CNV）为主要特征，而引起视力下降的主要原因是CNV引起的黄斑区反复出血、渗出、瘢痕改变，视力预后极差。经瞳孔温热疗法（TTT）是一种治疗继发于AMD的CNV的较新方法，采用直径可调节的大光斑，穿透深的激光连续照射，使靶组织缓慢升温，在消除CNV病灶的同时又相对保存病变表面视网膜的结构和功能。就TTT治疗AMD的应用发展、特点、临床疗效、治疗方法以及可能出现的并发症等作一综述。     

Treatment according to "evidence-based medicine" of aged-related exudative age-related macular degeneration (laser photocoagulation and photodynamic therapy)]

INTRODUCTION: Age related macular degeneration (AMD) is actually the leading cause of severe visual acuity loss in people over 65 in the Western World. Most of the visual loss is due to choroidal neovascularization (CNV). METHODS: Review of the literature. RESULTS: For more then 10 years laser photocoagulation was the only proven treatment for selected cases of AMD according to the evidence based medicine criteria. In 1999 photodynamic therapy was proven to be efficient for the treatment of predominantly classic subfoveal CNV. CONCLUSION: Laser photocoagulation and photodynamic therapy constitute therefore the only evidence based medicine treatment available for CNV in AMD.     

光动力疗法治疗渗出型老年性黄斑变性的初步报告

目的 观察单次光动力治疗(photodynamic therapy,PDT)对渗出型老年性黄斑变性(age-related macular degeneration,AMD)脉络膜新生血管(choroidal neovascularization,CNV)的近期治疗效果。 方法 回顾分析经荧光素眼底血管造影(fundus fluorescein angiography, FFA)、吲哚青绿脉络膜血管造影(indocyanine green angiography, ICGA)以及光学相干断层扫描(optic coherence tomography,OCT)检查确诊的5例渗出型AMD患者的7只患眼行PDT治疗前及治疗后随访观察1周和1个月时的临床资料,主要以视力、FFA及(或)ICGA、OCT的改变为观察指标,评价PDT对渗出型AMD的治疗效果。 结果 7只患眼在治疗后1个月视力均无下降。治疗后1周时除1只眼在ICGA后期仍可观察到CNV有轻微渗漏外,其余6只眼FFA及(或)ICGA均显示CNV渗漏停止;OCT检查显示CNV有不同程度缩小,CNV周围视网膜脉络膜水肿及神经上皮脱离明显好转。但在治疗后1个月时观察到有2只眼在原渗漏病灶处又有渗漏灶出现。 结论PDT 治疗可以在短期内封闭AMD的CNV,使其停止渗漏,且不影响视力。(中华眼底病杂志,2000,16:213-216)     

光动力疗法治疗老年性黄斑变性合并脉络膜新生血管的临床观察

目的 观察单次光动力疗法(photodynamic therapy, PDT)治疗渗出型老年性黄斑变性(age-related macular degeneration, AMD)合并脉络膜新生血管(choroidal neovascularization, CNV)的短期治疗效果。 方法 回顾分析经荧光素眼底血管造影(fundus fluorescein angiography, FFA)、吲哚青绿血管造影(indocyanine green angiography,ICGA)和光相干断层成像术(optic coherence tomography, OCT)等检查确诊的30例渗出型AMD患者的35只患眼行PDT治疗前和治疗后1周,1、3个月的临床资料，以视力、FFA、ICGA和OCT检查结果为观察指标，评价PDT对渗出型AMD的短期治疗效果。 结果 治疗后3 个月内有34只眼视力不变或提高，1只眼因出血而视力下降；FFA检查显示有19只眼荧光素渗漏减轻或完全消退；OCT检查显示视网膜水肿和浆液性脱离明显好转。全部患者治疗过程中未发生任何不良反应；治疗后3例患者主诉有一过性视物变暗，2例主诉轻微背痛。 结论 PDT治疗渗出型AMD时，可短期封闭CNV，使渗漏减轻或消退，对视力无损害。 (中华眼底病杂志, 2002, 18: 171-174)