年龄相关性黄斑变性患者中心凹下脉络膜新生血管的verteporfin治疗 关于基线病损组成对视力结果影响的附加信息——TAP报道No.3

目的：探讨在年龄相关性黄斑变性(AMD)治疗及光动力学治疗研究中，行verteporfin(Visudyne)光动力治疗中心凹下脉络膜新生血管(CNV)的AMD患者基线病损组成对视力结果的影响。     

曲安奈德玻璃体内注射联合PDT治疗AMD患者中心凹下脉络膜新生血管[英]Rechtman E…／／Br J Ophthalmol

目前，对年龄相关性黄斑变性(AMD)患者中心凹下脉络膜新生血管(CNV)的治疗，仅维替泊芬(verteporfin)的光动力学疗法(PDT)和激光凝固治疗有确实效果。曲安奈德作为常用类固醇药物，是已知的最具潜力的抗新生血管药物。目前尚鲜见有关曲安奈德玻璃体内注射(intravitreal triamcinolone acetonide，iTAAC)联合PDT治疗AMD患者CNV的报道。     

影响抗血管内皮生成因子治疗渗出型老年性黄斑变性预后的因素

玻璃体腔注射抗血管内皮生长因子(VEGF)药物是治疗渗出型老年性黄斑变性(AMD)脉络膜新生血管(CNV)的安全有效方法.但基线视力、年龄、首发症状、开始治疗的时间、对最初3次治疗的反应以及光相干断层扫描、荧光素眼底血管造影、眼底自身荧光检查结果不同的患者,其治疗预后差异较大;除了上述临床特征和指标外,基因及生物学标记物方面的差异对治疗预后也有影响.探讨影响渗出型AMD患者抗VEGF治疗预后众多相关因素中的主要因素并采取相应的对策,对于提升抗VEGF药物治疗效果具有积极意义.     

光动力疗法在抗血管内皮生长因子时代的存在价值

新生血管类眼底疾病是导致患者中心视力严重丧失的常见原因之一.血管内皮生长因子(VEGF)在病理性新生血管的发病过程中起着非常重要的作用.近年来,抗VEGF药物的研发及广泛的临床应用改变了很多新生血管类疾病的预后,使这类疾病的治疗逐步进入了抗VEGF时代,特别是对以脉络膜新生血管(CNV)为主要病理改变的湿性年龄相关性黄斑变性(wAMD)疾病的治疗取得了突破性的进展,改变了既往以光动力疗法(PDT)为主的wAMD治疗模式.虽然PDT在AMD治疗中退居次要地位,但仍然具有存在的意义,对于特殊情况下的AMD和特殊的CNV病灶,以及一些特定疾病的治疗具有重要价值.     

从VEGF在湿性年龄相关性黄斑变性发病过程中的作用机制看抗VEGF药物治疗

年龄相关性黄斑变性(AMD)的发病机制较复杂,其中湿性AMD对视力的威胁更为严重,其主要病理特征是黄斑区脉络膜的新生血管形成,血管内皮细胞生长因子( VEGF)在发病和新生血管的发展过程中发挥着重要作用.湿性AMD的物理治疗方法较多,但均无法改善患者的视力,近年来拮抗VEGF作用的药物疗法成为湿性AMD治疗的新途径.抗VEGF单克隆抗体是目前临床上应用较多的药物,能够消除新生血管,改善患者视力.针对VEGF其他环节的药物,如VEGF捕获剂、小分子干扰RNA及酪氨酸激酶抑制剂等,正处于试验阶段,其治疗效果值得期待.由于这些药物均为抗VEGF的制剂,因此充分了解VEGF在湿性AMD发病和发展过程中的作用机制有助于合理使用这些药物.     

玻璃体腔内注射Bevacizumab联合白内障手术治疗湿性年龄相关性黄斑变性(英文)

目的:探讨玻璃体腔内注射bevacizumab (Avastin)联合白内障手术预防脉络膜新生血管(choroidal neovascularization,CNV)的再次激活及年龄相关性黄斑变性(age-relatedmacular degeneration, AMD)。方法:对12例接受湿性年龄相关变性治疗的白内障患者给予透明角膜切口白内障超声乳化和人工晶状体植入手术,最后予以玻璃体腔内注射1.25mg bevacizumab (0.05mL)。主要评价指标:视力恢复、脉络膜新生血管的再次激活,及相干光断层成相术(OCT)对渗漏液体的评估。结果:患者最佳矫正视力(best-corrected visual acuity, BCVA)术后显著提高(脉络膜新生血管闭合后P<0.01,白内障发生后P=0.049,t检验)。白内障术后平均随访时间为11.8mo(标准差6.1,范围3 ～22mo),随访期内患者未出现脉络膜新生血管的再次激活及新的脉络膜新生血管病变。结论:在给予脉络膜新生血管及年龄相关性黄斑变性治疗的患者,白内障手术联合玻璃体腔内注射bevacizumab可预防脉络膜新生血管的再次激活。     

渗出型老年性黄斑变性治疗药物的研究进展

抗血管内皮生长因子(VEGF)生物制剂ranibizumab(商品名Lucentis)、pegaptanib（商品名Macugen）等的临床应用，改变了渗出型老年性黄斑变性(AMD)等脉络膜新生血管(CNV)疾病药物治疗的格局，但需要长时间反复玻璃体腔注射是其主要缺点。一些新型的VEGF受体融合蛋白、络氨酸激酶抑制剂、RNA干扰分子、调节细胞生长和代谢的sirolimus、整合素(integrin)拮抗剂以及基因治疗均引起了研究者关注，而且有些已经显露出良好的应用前景。随着对眼部新生血管机制研究的进一步深入，有望开发一些针对新生血管整个信号传递多个环节的治疗药物，或通过基因治疗手段在AMD病灶区域长久表达抗血管生成药物，为AMD的药物治疗带来了新的希望。     

年龄相关性黄斑变性脉络膜新生血管的抗VEGF治疗

血管内皮生长因子(VEGF)是最重要的影响新生血管形成的因子，在年龄相关性黄斑变性的脉络膜新生血管形成中有重要作用。抗VEGF药物可抑制CNV的产生，从而起治疗作用。本文就VEGF及其受体的生理及病理作用，以及近两年来出现的抗VGF治疗AMD的进展做一综述。     

与年龄有关的黄斑变性(老年性黄斑变性)脉络膜新生血管化的诊断和激光治疗

与年龄有关的黄斑变性(老年性黄斑变性)是西方国家60岁以上成年人视力丧失的首要原因。本病早期表现为黄斑玻璃膜疣和视网膜色素上皮轻度萎缩,视力可无改变或轻度下降。此期没有专门有效的药物或外科治疗能纠正其视力下降。大多数与年龄有关的黄斑变性(AMD)病人只有轻度视力障碍。有些病人玻璃膜疣及视网膜色素上皮萎缩区融合,并会引起中心视力的严重丧失。约10%AMD 病人视力降至20/200或更差,其病眼只有一些萎缩性改变。而90%的病人视力更严重下降的原因是异常的新生血管从脉络膜长入视网膜(脉络膜新生血管化或新生血管膜)。不经治疗,新生血管膜在黄斑形成瘢痕组织并由此导致中心视力的永久丧失。早期脉络膜新生血管形成引起感觉视网膜浆液性脱离,视网膜下出血和呈灰绿色的视网膜色素上皮脱色改变,硬性渗出(脂质沉着)在此期也很常见。这时作荧光血管造影可见强荧光充盈新生血管膜及渗漏勾画出了新生血管区域的轮廓。如果在新生血管长入中心黄斑区或瘢痕组织形成前就发现,可用激光作光凝治疗。以最近的荧光血管造影为指导,用强激光对整个新生血管区作光凝。在新生血管长入黄斑中心或瘢痕组织形成以前就作激光治疗可使严重视力障碍的危险降低50%以上。应对有发生新生血管危险的病人进行监视,对有新生血管形成早期体征和症状的病人应给予充分评价。     

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.     

Verteporfin PDT for non-standard indications—a review of current literature

Background  

Verteporfin photodynamic therapy (PDT) is approved for the treatment of predominantly classic subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD), as well as for subfoveal CNV due to pathologic myopia and ocular histoplasmosis syndrome. Verteporfin PDT addresses the underlying pathology of ocular vascular disorders through its angio-occlusive mechanism of action, which reduces both visual acuity loss and the underlying leakage associated with lesions. Verteporfin PDT has also been associated with encouraging treatment outcomes in case studies involving patients with choroidal vascular disorders such as polypoidal choroidal vasculopathy, central serous chorioretinopathy, choroidal haemangioma, angioid streaks, and inflammatory CNV, i.e. conditions currently considered as non-standard indications of verteporfin PDT. In many studies, outcomes were better than expected based on the natural courses of each of these conditions. Although the anti-vascular endothelial growth factor (VEGF) therapies, ranibizumab and pegaptanib, have been approved for CNV due to AMD, their role in these other choroidal vascular disorders remains to be established. We summarize current literature that has documented the use of verteporfin PDT in these conditions.     

Photodynamic therapy for choroidal neovascular disease: photosensitizers and clinical trials

Photodynamic therapy with visudyne for choroidal neovascular disease (CNV) has proved effective at preventing moderate to severe visual loss in eyes with subfoveal predominantly classic CNV or occult-only CNV caused by age-related macular degeneration (AMD) and in eyes with subfoveal CNV caused by pathologic myopia. PDT is not meant to improve visual acuity. It should, therefore, be used in eyes with potentially useful macular vision. Clinical trials are under way to evaluate the usefulness of early retreatment with PDT and visudyne at 6 weeks for reducing the risk for moderate visual loss in eyes with predominantly classic CNV, the efficacy of PDT with visudyne for the treatment of AMD in eyes with minimally classic CNV, and the efficacy of PDT for use with SnET2, lutetium texaphyrin, and Npe6.     

Use of intravitreal injection of triamcinolone acetonide in the treatment of age-related macular degeneration

Age-related macular degeneration (AMD) is now considered an important and leading cause of blindness among elderly patients in developed and developing countries. AMD has two forms, dry and wet; both can lead to visual loss. However, occurrence of subfoveal choroidal neovascular (CNV) membrane in the wet form results in severe visual impairment. Treatment options for choroidal neovascularization are available in order to maintain and in some cases improve vision. Photodynamic therapy (PDT) has been used to treat both classic and occult membranes. It has known to cause choroidal hypoperfusion and production of vascular endothelial growth factor. Intravitreal steroid can possibly reduce the damage caused due to these undesirable effects. In the recent past, intravitreal injection of triamcinolone acetonide (IVTA) has been used extensively as an adjunct to PDT in AMD in order to reduce the number of PDT sessions and evaluate possible beneficial effects on vision. This article reviews the pharmacological attributes of triamcinolone, available evidence of its use as monotherapy or combination therapy to treat AMD, ocular side-effects thereof and ongoing clinical trials on IVTA.     

Macular microcirculation blood flow in patients with age related macular degeneration treated with photodynamic therapy and transpupillary thermotherapy

PURPOSE: To assess the macular retinal and choroidal microcirculation blood flow in patients with exudative age related macular degeneration before and after photodynamic therapy (PDT) or transpupillary thermotherapy (TTT) with Doppler laser scanning (HRF--Heidelberg retinal flowmeter). MATERIAL AND METHODS: Thirty patients with exudative age-related macular degeneration were included in a prospective study. The diagnosis was established based on ophthalmic examination and fluorescein angiography results. In all cases the subfoveal choroidal neovascularization (CNV) was present. Control group consists of the fellow eyes with early stage of AMD (19 eyes) or with disciform scar (11 eyes). In 15 eyes with active CNV PDT was performed and in remaining 15--TTT. In all cases the macular blood flow was measured with Heidelberg retina flowmeter (HRF) before therapy and then 1 week, 4 weeks and 10-12 weeks after treatment. RESULTS: At the baseline examination in a group of eyes with active CNV the mean values of macular blood flow were significantly higher comparing to the fellow eyes and reached respectively: 678.6 +/- 125.0 AU and 298.4 +/- 79.2 AU (p=0.001). Four weeks after treatment all eyes showed the reduction of macular blood flow comparing to the baseline values (p=0.001). Ten to twelve weeks after laser therapy in all cases the increased macular blood flow was detected comparing to the previous examination (p=0.01). During the follow-up period the macular blood flow in the fellow eyes were significantly lower than in treated eyes. CONCLUSIONS: The measurement of macular blood flow using Doppler scanning laser (HRF--Heidelberg retinal flowmeter) may act as a non-invasive and useful diagnostic tool in assessment of CNV activity in patients with exudative age-related degeneration before and after PDT or TTT.     

Serous Retinal Detachment Following Combined Photodynamic Therapy and Intravitreal Bevacizumab Injection

We report a case of serous retinal detachment following combined photodynamic therapy (PDT) and intravitreal bevacizumab injection in subfoveal choroidal neovascularization (CNV).A 53-year-old woman was diagnosed with subfoveal CNV secondary to age-related macular degeneration (AMD) and treated with combined PDT and intravitreal bevacizumab injection. One day after treatment, the patient experienced a sudden decline of vision and optical coherence tomography (OCT) showed serous retinal detachment involving the macula. She was managed conservatively with an oral steroid beginning on the second day of the combined treatment and the subretinal fluid started to decrease one week following the initiation of steroids.This case suggests that combined PDT and intravitreal injection of bevacizumab can be associated with serous retinal detachment. Additional studies are needed to establish the safety and complications following this treatment regimen.     

Photodynamic therapy. Minimally invasive treatment of choroidal neovascularization

Summary The exudative stage of age-related macular degeneration (AMD) with choroidal neovascularization (CNV) commonly leads to rapidly progressive visual loss. Conventional laser coagulation with its unspecific destruction of the CNV, including adjacent retinal structures, often causes an additional reduction in visual acuity, particularly in cases with central localization of the pathological process. Photodynamic therapy (PDT) induces selective occlusion of CNV via light-induced pharmacological thrombosis without any damage to the retina in the macular area. Pilot studies have demonstrated complete occlusion of CNV with subsequent restoration of retinal function. Even repeated application was not associated with any alteration of the photoreceptor layer. The treatment strategy in PDT consists of repetitive thrombosis of CNV with progressive occlusion of the exudative lesion adjusted to the angiographic appearance. A randomized multicenter trial is currently underway and is evaluating the long-term visual results documented in 609 patients with subfoveal CNV who underwent control and eventual PDT at 3-month intervals. If PDT proves to be beneficial, an easy and non-invasive treatment modality could be offerted to numerous patients who demonstrated occult classic CNV and are otherwise facing an extremely poor prognosis.      

Case series outcomes at 1 week following verteporfin photodynamic therapy.

PURPOSE: To examine the choroidal neovascularization (CNV) fluorescein angiographic perfusion and visual acuity 1 week after photodynamic therapy (PDT) with verteporfin (Visudyne, Novartis AG, Switzerland) on predominantly classic, subfoveal lesions in age-related macular degeneration (AMD). METHOD: A retrospective case series study was conducted on the 1-week outcome of PDT treatment of 76 of 79 consecutive patients with the subfoveal, predominantly classic CNV form of AMD. Leakage from CNV was assessed by fluorescein angiography and best-corrected visual acuity determined on projected Snellen charts using a standardized protocol. RESULTS: One week after PDT treatment, absence of fluorescein leakage from CNV was observed in 100% of the 76 patients. Visual acuity improved (at least a three-line gain) in 11 patients (15%), remained unchanged (less than a three-line gain or loss) in 64 patients (84%), and deteriorated (at least a three-line loss) in only one patient (1%). CONCLUSION: The absence of fluorescein leakage from classic CNV at 1 week in all cases was consistent with the published outcome of the clinical Phase I and II PDT trials. Further, vision loss 1 week after PDT for predominantly classic CNV was very uncommon. Therefore 1-week post-PDT angiography is unnecessary for predominantly classic CNV in patients with AMD.     

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.     

渗出型老年性黄斑变性患者光动力疗法治疗前后视功能变化

目的 观察渗出型老年性黄斑变性（AMD）患者光动力疗法（PDT） 治疗前后的视功能变化。 方法 对经临床眼底检查、荧光素眼底血管造影（FFA）、吲哚青绿血管造影（ICGA）和光相干断层扫描（OCT）检查确诊的AMD患者25例34只眼采取PDT治疗，治疗后随访4个月～2年，平均随访观察时间9.2个月。对比分析治疗前以及治疗后定期随诊观察的最佳视力［采用最小分辨角度的对数视力(logMRA)统计平均视力］、视物变形及中心暗点、对比敏感度、双眼单视功能和立体视功能、以及色觉辨认等的变化情况。 结果 PDT治疗前患眼平均视力为logMAR 0.73±0. 37，治疗后不同时期的平均视力较治疗前提高，尤其在3个月时较明显，其平均视力logMAR 0.59±0.45。治疗前后比较，差异无显著性的意义（P＞0.05）；其中视力提高者13只眼 ，占38.24%；无变化15只眼，占44.12%；下降6只眼，占17.65%。Amsler方格表检查视物变形和中心暗点均较治疗前范围缩小，但差异无显著性的意义（P＞0.05）。治疗后各频区的对比敏感度值均较治疗前呈现不同程度提高，低频区（1.5 c/d）差异有显著性的意义（P＜0.05） 。患者的双眼同时视功能、融合功能、立体视功能以及色觉辨认功能均较治疗前有轻度改善 （P＞0.05）。 结论 渗出型AMD患者的视功能变化是多方面的，PDT 治疗可改善患者的部分视功能. （中华眼底病杂志，2004，20：289-291）     

Photodynamic therapy with verteporfin in age‐related macular degeneration: a systematic review of efficacy,safety, treatment modifications and pharmacoeconomic properties

Photodynamic therapy (PDT) with verteporfin has been used less comprehensively in the treatment of exudative age‐related macular degeneration (AMD), and specifically of choroidal neovascularization (CNV), since the advent of antiangiogenic therapies. Recently, there has been a renewed interest in PDT as an adjunct to these and other agents in the treatment of neovascular AMD. In light of this new development and the European Medicines Evaluation Agency’s (EMEA) recent labelling decision to rescind approval for the use of PDT in occult CNV lesions, the present systematic review was undertaken to revisit the evidence supporting its clinical application. Photodynamic therapy provided the first pharmacological treatment for patients suffering from subfoveal CNV, the major cause of severe vision loss in AMD. Key clinical trials evaluating efficacy and safety have examined patients with all lesion subtypes, with the primary labelled indication (i.e. lesions containing a classic component of ≥ 50% ) deriving from the results of the Treatment of Age‐related Macular Degeneration with Photodynamic Therapy (TAP) Study. The subsequent TAP Study Group post hoc categorization of lesions as predominantly classic is open to question, however, as it appears that the overall efficacy in this group only may have reflected the especially strong response in 100% classic lesions. Based on a subgroup analysis of the Verteporfin in Photodynamic Therapy Study, the indication for PDT subsequently was expanded in some jurisdictions, including that of the EMEA, to include occult lesions with no classic component. However, the subsequent Visudyne in Occult Study found no benefit in 100% occult lesions, resulting in the EMEA rescinding its approval for this indication.