视网膜血管瘤样增生的诊断与治疗

视网膜血管瘤样增生(retinal angiomatous proliferation,RAP)是湿性老年性黄斑变性(age-related macular degeneration,AMD)隐匿性新生血管的另一种病变形式,起源于黄斑旁视网膜深层毛细血管层,以多发性小灶状视网膜内出血、视网膜色素上皮脱离(pigment epithelial detachment,PED)、视网膜-脉络膜血管吻合(retinal-choroidal anastomosis,RCA)为特点,对视力损害严重。本文对近年来的有关文献进行复习,并就RAP的发病机制、临床分期、诊断特点、治疗及预后进行综述。     

视网膜血管瘤样增生的研究概况

视网膜血管瘤样增生(RAP)是年龄相关性黄斑变性的一种特殊类型,它起源于黄斑旁视网膜深层毛细血管网,并能不断增殖突破视网膜下间隙最终与脉络膜血管吻合.本文就视网膜血管瘤样增生的研究历程、分期、临床表现、诊断及治疗现状作一综述.     

抗眼底新生血管药物的研究进展

视网膜和脉络膜新生血管可引发玻璃体出血、视网膜下出血、牵引性视网膜脱离等,从而危害患眼视力。这类病变常见于老年性黄斑变性(age related macular degeneration,AMD)、糖尿病视网膜病变(diabetic retinopathy,DR)、视网膜静脉阻塞(retinal vein occlusions,RVO)、早产儿视网膜病变(retinopathy of prematurity,ROP)等眼底病。当前,药物治疗新生血管(neovscularization,NV)主要是针对NV生成的不同阶段抑制其生长。本文综述了目前已用于临床及正在进行临床试验的治疗眼底新生血管的药物。     

光动力疗法联合玻璃体腔注射抗血管内皮生长因子单克隆抗体ranibizumab治疗视网膜血管瘤样增生的疗效观察

视网膜血管瘤样增生(RAP)是近年来被认同的一种渗出型老年性黄斑变性( AMD)的特殊类型[1].其表现为深层视网膜内血管异常及视网膜-视网膜或视网膜-脉络膜血管吻合[2-5].RAP自然预后不良,其治疗也尚处于探索阶段.无论是对异常血管团直接激光光凝、激光光凝其滋养血管、光动力疗法(PDT)或经瞳孔温热疗法效果均不理想[6].我们采用PDT联合玻璃体腔注射抗血管内皮生长因子单克隆抗体ranibizumab(商品名Lucentis)对一组RAP患者进行了治疗.现将其结果报道如下.     

视网膜血管瘤样增生的眼底影像特征

自Hartnett等[1]首次描述了发生于老年性黄斑变性(AMD)患者“深层视网膜血管异常复合体”以来,视网膜血管瘤样增生( RAP)逐渐被认可为一种渗出型AMD的特殊类型[2,3].与其他类型的AMD不同,RAP的新生血管来源于视网膜深层毛细血管,并纵行向视网膜下腔发展,形成视网膜脉络膜吻合.Yannuzi等[4 ]研究发现,RAP常发生于白人,亚洲人中并不常见;且国内关于该病的报道也较少.为此,我们观察了一组RAP患者的影像学特征,现将结果报道如下.     

视网膜血管瘤增殖的研究进展

视网膜血管瘤增殖是近年来开始为人们所认识的一类新型新生血管性年龄相关性黄斑变性，它起源于黄斑旁视网膜深层毛细血管网并能不断增殖，向后突破入视网膜下间隙，最终与脉络膜新生血管形成吻合。本文对视网膜血管瘤增殖的分期、临床表现以及治疗方法作一综述。[眼科新进展2007；27（2）：150-154]     

近视性黄斑病变黄斑结构和微循环的变化及其与视力的相关性分析

目的：观察近视性黄斑病变(MM)黄斑区形态结构和微循环的变化,探讨其相关性及对视力的影响。

方法：病例对照研究。选取2016-10/2018-12于眼科检查的高度近视患者165例189眼,健康志愿者(正常对照组)154例154眼纳入研究。根据病理性近视荟萃分析(META-PM)分类方法将患者分为M0组(分类0,41眼),M1组(分类1,53眼),M2组(分类2和分类3,52眼),近视脉络膜新生血管(mCNV)组(43眼)。所有受检者均进行OCTA检查。对比组间视网膜不同分层形态学参数和微循环指标的差异,形态学参数与微循环的相关性采用Pearson相关性分析,多元线性回归分析视力与其他参数的相关性。

结果：M0组、M1组、M2组中心区全层视网膜厚度(FRT),外层视网膜厚度(ORT)均低于正常对照组(均P<0.01),M2组、mCNV组中心区表层视网膜血流密度(SVD)、深层视网膜血流密度(DVD)均低于正常对照组(均P<0.01); M0组、M1组、M2组、mCNV组旁中心区FRT、ORT均低于正常对照组(均P<0.01),M2组、mCNV组旁中心区内层视网膜厚度(IRT)、SVD、DVD均低于正常对照组(均P<0.01); M0组、M1组、M2组、mCNV组黄斑中心凹下脉络膜厚度(SFCT)、脉络膜毛细血管层血流密度(CVD)均低于正常对照组(均P<0.01)。近视性黄斑病变不合并CNV眼中心区视网膜及脉络膜血流密度与对应的视网膜脉络膜厚度呈正相关(均P<0.05)。多因素分析结果显示,轴长(AL)、弥漫性或斑片状脉络膜视网膜萎缩是最佳矫正视力(BCVA)的影响因素(均P<0.01)。

结论：近视性黄斑病变视网膜形态学改变早于微循环改变,且外层视网膜厚度改变早于内层视网膜厚度改变。中心区视网膜和脉络膜血流密度与对应的视网膜脉络膜厚度呈正相关。BCVA的影响因素主要为AL和近视性黄斑病变类型。     

视网膜血管瘤样增生的研究概况

视网膜血管瘤样增生(retinalangiomatousproliferation,RAP)是年龄相关性黄斑变性(ARMD)的一种特殊类型。通常意义上的ARMD起源于脉络膜,而RAP起源于视网膜感觉层毛细血管。这种特殊类型的ARMD最近受到临床医师和研究人员的密切关注。本文就RAP的研究历程、临床表现、病理学特点、形成机制、分期及诊断和治疗现状进行综述。     

年龄相关性黄斑变性视网膜血管瘤性增生的治疗 104例视网膜血管瘤性增生病例

目的：视网膜血管瘤性增生（RAP）是新近描述的一种在年龄相关性黄斑变性患者的视网膜内出现的新生血管性病灶，本文主要报道控制视网膜血管瘤性增生（RAP）的治疗措施。     

骨桥蛋白与眼部新生血管性疾病研究进展

眼部新生血管是眼部疾病中致盲的主要原因之一.常见的致盲眼病,如糖尿病视网膜病变、年龄相关性黄斑变性、感染性角膜炎等均与新生血管存在一定的关系.骨桥蛋白（OPN）是一种能够促进血管再生与组织修复的糖蛋白,在角膜、脉络膜和视网膜新生血管中表达增多,能够促进新生血管的发生.OPN与新生血管的关系为新生血管性疾病的研究和治疗提供了新的方向.从OPN促进角膜新生血管、脉络膜新生血管、视网膜新生血管生成3个方面对OPN与眼部新生血管性疾病的关系研究进展进行综述.     

Nature and risk of neovascularization in the fellow eye of patients with unilateral retinal angiomatous proliferation

PURPOSE: To determine the nature and risk of neovascularization in the fellow eyes of patients with unilateral retinal angiomatous proliferation (RAP), a neovascular form of age-related macular degeneration (AMD). METHODS: A consecutive series of 52 patients diagnosed with unilateral RAP were studied retrospectively. Clinical biomicroscopic examination, fluorescein angiography, and indocyanine green angiography were used to evaluate all patients for the development of neovascular manifestations in the fellow eye. RESULTS: Neovascularization developed in the fellow eye in 52 patients over the follow-up period (range, 2-36 months). All patients developed neovascular manifestations of RAP in the fellow eye. Twenty-one patients (40%) developed a RAP lesion within 1 year; 29 (56%), within 2 years; and 52 (100%), within 3 years. At the time of diagnosis of neovascularization in the fellow eye, 8 patients (15%) had a stage I RAP lesion, 36 (70%) had a stage II RAP lesion, and 8 (15%) had a stage III RAP lesion. Other characteristic findings in these patients included the presence of preretinal, intraretinal, and subretinal hemorrhages in 49 patients (94%) and pigment epithelial detachments in 41 patients (79%). CONCLUSIONS: In patients diagnosed with unilateral RAP lesions, the form of neovascularization that develops in the fellow eye is virtually always RAP. The annual and accumulative risk of neovascularization in the fellow eye is higher in patients with RAP than in those with other forms of neovascular AMD. These new findings enhance our understanding of the clinical spectrum of RAP in terms of its natural course and visual prognosis and may possibly offer useful information to establish future treatment options.     

Optical coherence tomography (OCT) angiomatous prolifieration (RAP) in retinal

PURPOSE: To verify the utility of optical coherence tomography (OCT) for diagnosing retinal angiomatous proliferations (RAP) in patients with exudative age-related macular degeneration (AMD). METHODS: Multiple cross-sections were taken with OCT from 41 eyes of 39 consecutive patients with AMD and RAP. The presence and the location of the angiomatous complexes had already been documented by fluorescein angiography (FA) and high-speed confocal indocyanine green videoangiography (ICGA). RESULTS: RAP was detectable by OCT scans in all 41 eyes, appearing as a focal hyper-reflecting area in the neuroretinal layers; it was frequently located close to the inner surface of the retinal pigment epithelium (29 eyes [70. 7%]). All eyes had either no or only a low-reflecting OCTsignal surrounding the RAP, caused by serous intraretinal edema. Only 13 eyes (31.7%), however, had large serous retinal detachment (SRD). OCT detected pigment epithelium detachment in 31 eyes (75.6%), but none had underlying choroidal neovascularization. CONCLUSIONS: OCT findings confirm the intraretinal localization of the RAP which are always associated with impressive exudative phenomena. OCT is therefore a useful diagnostic tool, adding information to FA and high-speed ICGA.     

Retinal angiomatous proliferation with a cilioretinal artery anastomosis: an unusual presentation

Purpose To report an unusual phenotype of retinal angiomatous proliferation (RAP) in age-related macular degeneration (AMD) and its short-term response to laser photocoagulation.Methods Case report.Results An 85-year-old woman was found to have an unusual RAP with a major feeder vessel originating from a cilioretinal artery and associated with a cilioretinal–retinal anastomosis (C-RRA). Diffuse cystoid macular edema (CME), intraretinal hard exudates in a circinate pattern, and a fibrovascular pigment epithelial detachment (PED) were present. Laser photocoagulation was performed and led to occlusion of the cilioretinal feeder vessel and angiomatous lesion, with less CME. The other (retinal) arm of the C-RRA became more engorged and a new cilioretinal feeder developed, and both were associated with intraretinal hemorrhages. Visual acuity was stable and the PED persisted throughout follow-up.Conclusions We report an unusual phenotype of RAP that is associated with a major cilioretinal feeder vessel and comment on the possible effect of such an association on the response to laser treatment.     

Surgical ablation of retinal angiomatous proliferation

Age-related macular degeneration (AMD) remains the leading cause of visual loss in adults older than 65 years. Retinal angiomatous proliferation (RAP) is a newly recognized manifestation of exudative AMD that has a poor natural history and demonstrated resistance to treatment with conventional laser photocoagulation. A novel surgical technique has been developed in this pilot series that shows promise in the treatment of this subtype of neovascular lesions. Through specific surgical lysis of the feeding arteriole and draining venule of an RAP lesion, improvement in visual acuity has been noted. This has been correlated with resolution of intraretinal edema and flattening of associated pigment epithelial detachment, which was confirmed by fluorescein angiography, optical coherence tomography, and high-speed indocyanine green angiography.     

Clinicopathological findings of retinal angiomatous proliferation

Background Neovascular membranes obtained from surgical excision of neovascularization for retinal angiomatous proliferation (RAP) were examined histopathologically in an attempt to elucidate the pathogenic mechanism of RAP. Methods Nine eyes of eight patients (mean age, 79±6 years) who underwent neovascularization excision were studied. Three eyes had stage II with RPE detachment, six had stage III. Immunohistochemical studies were performed to identify von Willebrand factor, vascular endothelial factor (VEGF), CD68 and hypoxia inducible factors (HIF-1 alpha and HIF-2 alpha). Results Multiple soft drusen were present in the macular area in all patients. In one stage II eye, we observed intraretinal neovascularization as a VEGF-positive mass, CD68-positive macrophage migration and HIF expression. In another stage II eye, neovascularization had extended above the RPE, while VEGF-positive fibroblasts were observed below the RPE. Therefore, in stage II, neither angiographic nor histopathological examinations identified choroidal neovascularization. In one phase III eye, angiography demonstrated choroidal neovascularization and chorioretinal anastomosis. Histopathologically, chorio-retinal communication was observed in the region where the RPE was destroyed, and VEGF-positive neovascularization was also seen below the RPE. Conclusions The findings of multiple drusen in elderly patients together with macrophage migration and HIF expression surrounding VEGF-positive retinal neovascularization suggest ischemic and inflammatory factors to be associated with the development and progression of RAP.     

High resolution Fourier-domain optical coherence tomography of retinal angiomatous proliferation

PURPOSE: To study the anatomic details of retinal angiomatous proliferation (RAP) in patients with age-related macular degeneration (AMD) using high-resolution Fourier-domain optical coherence tomography (Fd-OCT) and its three-dimensional reconstructions. METHODS: A Fd-OCT instrument was used to image five patients clinically diagnosed with RAP. A series of 100 raster-scanned B-scans centered over the macula was registered and rendered as a three-dimensional volume. These retinal structures were analyzed for anatomic details of the RAP lesions. RESULTS: The RAP lesion could be identified within the retina on Fd-OCT in all five cases. Fd-OCT images of the first four cases revealed areas of intraretinal neovascularization (IRN) in the deep retina adjacent to a pigment epithelial detachment (PED). There was neovascular proliferation anteriorly and posteriorly through a break in the retinal pigment epithelium (RPE). In three of the four cases, Bruch membrane remained intact. There was no identifiable choroidal neovascularization (CNV). The fifth case had both subretinal and sub-RPE neovascular membranes without a PED. CONCLUSION: Fd-OCT provides unprecedented in vivo detail of the anatomy of RAP lesions that nearly resembles histologic specimens. This study suggests that the initial neovascular process in RAP can originate either within the retina or in the sub-RPE space.     

年龄相关性黄斑变性脉络膜新生血管治疗的几个重要问题

近年来,在治疗年龄相关性黄斑变性导致的脉络膜新生血管方面取得了很大进展.但是,要取得良好的治疗效果,有几个问题必须明确.即典型性脉络膜新生血管还是隐匿性脉络膜新生血管,是否是息肉状脉络膜血管病变或是视网膜血管瘤样增生,治疗时选择光动力疗法还是抗血管内皮细胞生长因子疗法等.临床医师需对脉络膜新生血管各种治疗方法 的疗效和安全性有准确、全面的了解,才能取得满意的效果.(中华眼科杂志,2008,44:196-199)     

Subtype lesions of neovascular age-related macular degeneration in Chinese patients

Purpose To identify the subtype frequency and clinical features of neovascular age-related macular degeneration (AMD) in Chinese patients. Methods From January 2003 to August 2006, we investigated prospectively 155 newly diagnosed patients with presumed neovascular AMD. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed in both eyes of all patients. Subtype frequency and clinical features were recorded according to their angiograms. Results Three subtypes of lesion were noted, which were polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP) and mixed lesions. Of the 155 patients, 105 (67.7%) had choroidal neovascularization (CNV) of the typical type seen in AMD, 38 (24.5%) had PCV and seven (4.5%) had RAP. In five (3.2%) additional cases, mixed lesions were noted. In 38 cases (47 eyes) with PCV, the rates of subfoveal, juxtafoveal and extrafoveal lesion were respectively 29.8% (14 eyes), 8.5% (four eyes), and 61.7% (29 eyes), compared with 75.6%, 14.6% and 9.8% for CNV lesion (P < 0.01). The percentage of subfoveal lesion in PCV group was significantly lower than that in the CNV group (P < 0.01). The location of the RAP lesion was subfoveal in two (28.6%) eyes, juxtafoveal in three (42.9%) eyes and extrafoveal in two (28.6%) eyes. The five eyes with mixed lesions were all PCV coexisting with CNV at the same eye, and in all of the five cases, CNV was subfoveal while PCV was extrafoveal. Conclusions In this hospital-based study, PCV accounts for 24.5% of neovascular AMD and is the most common subtype, RAP is less frequent (4.5%), and mixed lesions are much less common in Chinese patients. PCV is least likely to involve the fovea in neovascular AMD. The authors have no proprietary interest. This study was supported by the Natural Science Foundation of Guangdong Province (grant no. 04009333) and the Research Fund of Guangdong Bureau of Chinese Medicine (grant no.20030086).