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]     

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。     

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。     

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。     

年龄相关性黄斑变性的药物治疗进展

年龄相关性黄斑变性（ ARMD）是发达国家中老年人群主要致盲眼病,其患病率逐年上升趋势。主要由视网膜色素上皮细胞和视网膜退行性变而引起的不可逆性的中心视力下降或丧失。近年来,对多种类型年龄相关性黄斑变性尤其是新生血管型的治疗已经进行了大量的多中心的临床实验观察,涌现出光动力疗法、激光光凝、黄斑下手术、经瞳孔温热治疗、放射治疗、中医药治疗等方法,本文就ARMD目前有关的药物治疗方法及其进展做一综述。     

年龄相关性黄斑变性治疗的研究进展

年龄相关性黄斑变性(age-relatecll macular degeneration,AMD)是发达国家老年人群的主要致盲性眼病,可能与遗传因素、环境因素等有关.随着人口老龄化的发展趋势,相关研究表明AMD逐渐成为我国主要的致盲性眼病.近年来出现了许多新的治疗方法.如抗血管内皮生长因子、光动力疗法、经瞳孔温热疗法、预防性治疗及基因治疗等.本文对近年治疗AMD的相关文献进行综述.     

渗出型年龄相关性黄斑变性治疗进展

年龄相关性黄斑变性(age-related macular degeneration,AMD)是老年人致盲和严重视力丧失的主要原因之一.AMD有萎缩型和渗出型2种,渗出型AMD的主要特征为脉络膜新生血管形成.目前,针对脉络膜新生血管的有效治疗措施主要包括激光治疗、放射疗法、糖皮质激素和抗新生血管因子玻璃体腔内注射、外科手术等.临床试验和病例报道广泛证实了这些方法的有效性.本文综述了治疗渗出型AMD的主要药物和方法的进展.     

年龄相关性黄斑变性治疗方法研究

年龄相关性黄斑变性(age-related macular degeneration,AMD)是一种导致老年人视力减退和失明的主要疾病,对老年人及其家庭成员的身心健康产生严重影响。我们在分析AMD临床特点及发病机制基础上,对目前应用于临床的最新AMD治疗方法进行综述,并对各种治疗方法的适应性和局限性进行阐述和说明。     

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.     

年龄相关性黄斑变性的治疗研究新进展

年龄相关性黄斑变性是一种随年龄增长而发病率逐渐上升的黄斑部疾病。主要由视网膜色素上皮细胞和视网膜退行性变而引起的不可逆性的中心视力下降或丧失。近年来,对多种类型年龄相关性黄斑变性尤其是新生血管型(age-related macular degeneration,ARMD)的治疗已经进行了大量的多中心的临床实验观察,涌现出光动力疗法、药物治疗、放射治疗、激光光凝、黄斑下手术、经瞳孔温热治疗、中医药治疗等方法,本文就ARMD目前有关的治疗方法及其进展做一综述。     

The prevalence of retinal angiomatous proliferation in age-related macular degeneration with occult choroidal neovascularization

Background The purpose of the study was to ascertain the prevalence of retinal angiomatous proliferation (RAP) by means of dynamic indocyanine green angiography (d-ICGA) in patients with newly diagnosed fibrovascular pigment epithelium detachment (type 1) or late leakage of undetermined source (type 2) occult choroidal neovascularization (CNV) on fluorescein angiography. Methods We carried out a review of digital fluorescein and ICG angiograms obtained by confocal scanning laser ophthalmoscope (HRA; Heidelberg Engineering GmbH, Dossenheim, Germany) in 253 consecutive patients (270 eyes) with a clinical diagnosis of type 1 or type 2 occult CNV on fluorescein angiography (1998 through 2003). Results Sixty eyes had type 1 and 210 eyes type 2 occult CNV on fluorescein angiography. Overall, 57 cases of RAP were identified in 54 eyes (20%) with d-ICGA. RAP was present in 6 out of 60 eyes with type 1 (10%) and in 51 out of 210 eyes with type 2 occult CNV (24%). Mean distance of the lesion from the fovea was 682 ± 304 μm (mean ± SD). Conclusions d-ICGA is invaluable for early diagnosis of RAP in exudative age-related macular degeneration (ARMD). In our series, up to one fourth of type 2 occult CNV were in fact RAP. Presented in part at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting, 2004, Fort Lauderdale, Florida, USA.     

Choroidal circulatory disturbances associated with retinal angiomatous proliferation on indocyanine green angiography

Purpose To investigate the association between choroidal perfusion and retinal angiomatous proliferation (RAP). Methods We performed indocyanine green angiography (ICGA) on 26 eyes of 13 consecutive patients with RAP, and 17 eyes of 17 age-matched controls without age-related macular degeneration. In eyes with RAP and concurrent pigment epithelial detachments (PEDs), we evaluated ICGA images obtained after the PEDs resolved following treatment. Of the 26 eyes in the study group, five eyes with stage 3 RAP or a disciform scar and two eyes that underwent photodynamic therapy were excluded from further evaluation, leaving 19 eyes (11 eyes with stage 1 or 2 RAP and eight fellow eyes without RAP). Results Early decreased choroidal filling (EDCF) was observed in nine (81.8%) of 11 eyes with RAP and five (62.5%) of eight fellow eyes without RAP. Late decreased choroidal filling (LDCF) occurred in nine (81.8%) of 11 eyes with RAP and four (50%) of eight fellow eyes without RAP. The incidence of EDCF and LDCF was significantly higher in eyes with RAP than in the control eyes (p < 0.05, p < 0.01, respectively). Conclusions Persistent decreased choroidal filling is common in early-stage RAP. Clinicians should be aware of this, especially when considering treatment. The authors have no financial interest in any aspect of this study.     

Subretinal surgery and transplantation of autologous pigment epithelial cells in retinal angiomatous proliferation

Purpose: The aim of this study was to examine whether the presence of retinal angiomatous proliferation (RAP) is a prognostic factor in subretinal surgery with transplantation of a suspension of autologous retinal pigment epithelial (RPE) cells. Methods: Eyes that had been followed for at least 12 months after subretinal surgery were reviewed retrospectively and assigned to group 1 (presence of RAP) or group 2 (lesions without RAP). Main outcome measures were logMAR distance acuity and lesion size at 12 months. Results: A total of 68 eyes of 68 patients were included; 28 were assigned to group 1 and 40 to group 2. A total of 43% of patients were male and 57% were female. Their mean age was 77.8 years. Mean distance acuity was 1.02 logMAR at baseline and 1.06 logMAR at month 12. Mean lesion size was 27.9 mm² at baseline and 29.9 mm² at month 12. The differences between the groups were not significant. Conclusions: The presence of RAP did not significantly influence the outcome after subretinal surgery with transplantation of autologous RPE cells. Other than age, preoperative lesion size and distance acuity were the only predictive factors for postoperative results.     

多次经瞳孔温热疗法的湿性年龄相关性黄斑变性视网膜色素上皮和脉络膜萎缩:病例报告

目的:报告1例湿性年龄相关性黄斑变性(AMD)在多次经瞳孔温热疗法(TTT)后,脉络膜新生血管(CNV)消退,但发生了视网膜色素上皮(PRE)和脉络膜的萎缩并伴低视力.方法:复习包括眼底照相、眼底荧光素血管造影(FFA)、靛青绿血管造影和干涉光断层扫描在内的临床资料.结果:男性72岁主诉左眼视物模糊,FFA证实为黄斑部息肉状脉络膜血管病变.其左眼的CNV未经任何治疗在6 a间保持0.1的视力.约2 a后,右眼出现一片CNV.在此后3a内,病灶保持或大(3×5 PD)或小(1×2 PD)并伴有明显渗出和出血,先后做了7次TTT,参数为80～280 mW、2 mm光斑、曝光60 s,每次间隔3 mo以上.CNV病灶最终消退,但黄斑部遗留白色区,视力由0.3降至0.04.结论:TTT可使CNV病灶消退,但可发生明显的RPE和脉络膜萎缩,这无益于视力.如果对亚洲患者应用TTT,其参数可低于120 mW/mm,限于2次.     

Retinal venular calibre dilatation after intravitreal ranibizumab treatment for neovascular age-related macular degeneration

Background: To describe the changes in retinal vascular calibre in response to intravitreal ranibizumab injections in patients with neovascular age‐related macular degeneration. Design: Prospective interventional case series. Participants: Treatment naïve patients with neovascular age‐related macular degeneration were recruited over a 1‐year period. Methods: Each patient received three monthly intravitreal injections according to a ‘loading dose’. Retinal arteriolar and venular calibre was measured from digital fundus photographs and summarized as central retinal artery equivalent and central retinal vein equivalent at baseline and 3 months. Main Outcome Measure: Central retinal artery equivalent and central retinal vein equivalent changes from baseline to 3 months. Results: Seventy‐four eyes of 71 patients had good quality images for grading vessel calibre at baseline and at 3 months in treated (study) eyes and 51 eyes of 51 patients had good quality images in fellow (control) eyes. Over 3 months, in study eyes treated with ranibizumab, there was a significant increase in central retinal vein equivalent over baseline (+6.20 µm, P = 0.005), but no significant change in central retinal artery equivalent (+0.86 µm, P = 0.55). In control eyes, there was no change in central retinal vein equivalent (?0.82 µm, P = 0.70) or central retinal artery equivalent (0.34 µm, P = 0.75). Conclusion: Intravitreal ranibizumab has a significant vasodilational effect on retinal venular calibre in eyes treated for neovascular age‐related macular degeneration. The reason for this change is unclear, but may relate to changes in blood flow or inflammatory changes within the retina.     

Combination of AIBP,apoA-I,and Aflibercept Overcomes Anti-VEGF Resistance in Neovascular AMD by Inhibiting Arteriolar Choroidal Neovascularization

PurposeAnti-VEGF resistance represents a major unmet clinical need in the management of choroidal neovascularization (CNV). We have previously reported that a combination of AIBP, apoA-I, and an anti-VEGF antibody overcomes anti-VEGF resistance in laser-induced CNV in old mice in prevention experiments. The purpose of this work is to conduct a more clinically relevant study to assess the efficacy of the combination of AIBP, apoA-I, and aflibercept in the treatment of anti-VEGF resistance of experimental CNV at different time points after laser photocoagulation.MethodsTo understand the pathobiology of anti-VEGF resistance, we performed comprehensive examinations of the vascular morphology of laser-induced CNV in young mice that are highly responsive to anti-VEGF treatment, and in old mice that are resistant to anti-VEGF therapy by indocyanine green angiography (ICGA), fluorescein angiography (FA), optical coherence tomography (OCT), and Alexa 568 isolectin labeled choroid flatmounts. We examined the efficacy of the combination therapy of AIBP, apoA-I, and aflibercept intravitreally delivered at 2, 4, and 7 days after laser photocoagulation in the treatment of CNV in old mice.ResultsLaser-induced CNV in young and old mice exhibited cardinal features of capillary and arteriolar CNV, respectively. The combination therapy and the aflibercept monotherapy were equally effective in treating capillary CNV in young mice. In old mice, the combination therapy was effective in treating anti-VEGF resistance by potently inhibiting arteriolar CNV, whereas aflibercept monotherapy was ineffective.ConclusionsCombination therapy of AIBP, apoA-I, and aflibercept overcomes anti-VEGF resistance in experimental CNV in old mice by inhibiting arteriolar CNV.     

Photodynamic therapy with verteporfin in Japanese patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD): Results of the Japanese AMD Trial (JAT) extension

Purpose To evaluate the longer term safety of verteporfin therapy in Japanese patients with subfoveal classic choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). Methods Patients completing 12 months of the Japanese AMD Trial (JAT) were eligible to enter the extension phase if the investigator judged they would potentially benefit from further verteporfin therapy. Patients had follow-up visits every 3 months, receiving verteporfin therapy in the study eye if leakage from CNV was observed on fluorescein angiography. Mean change from baseline in best-corrected visual acuity was a safety variable in the extension. Results Of the 51 patients entering the study extension, 46 (90%) completed 24 months. Adverse events were similar to those in the first 12 months of JAT; no cumulative toxic effect of verteporfin therapy was identified. Mean visual acuity letter score in the study eye increased from 50.8 (20/100⁺¹ at baseline to 54.0 (20/80⁻¹) at month 24. At month 24, six patients (13%) had lost 15 or more letters of visual acuity, of whom four (9%) had lost 30 or more letters. Conclusion Verteporfin therapy was shown to be safe and effective through 24 months in Japanese patients with subfoveal CNV due to AMD, supporting its long-term use in these patients. A complete list of the participants in the Japanes Age-Related Macular Degeneration Trial Study Group is available in Am J Ophthalmol 2003;136:1049–1061.     

Retinal angiomatous proliferation responds safely to a double dose (1.0 mg) of ranibizumab

A 77‐year‐old man presented with sudden foggy central vision in the right eye. The visual acuity (VA) was 6/60 (R) and 6/6 (L). Funduscopy revealed superficial macular haemorrhage in the right eye. Using fluorescein angiography and indocyanine green angiography, retinal angiomatous proliferation was confirmed. Two intra‐vitreal injections of bevacizumab were given but the VA did not improve. Following this, he received an intra‐vitreal injection of ranibizumab. Regression of the retinal angiomatous proliferation was observed and the VA of the right eye returned to 6/10. Simultaneously, his left eye suffered from sudden visual loss and retinal angiomatous proliferation was diagnosed. Three intra‐vitreal injections of ranibizumab were given. Regression of the retinal angiomatous proliferation was observed and the VA of the left eye was stabilised. Another 80‐year‐old man complained of sudden distorted vision in his left eye. Funduscopy and optical coherence tomography (OCT) revealed superficial macular haemorrhage and retinal pigment epithelial detachment (RPED). The VA was 6/12 and retinal angiomatous proliferation was diagnosed. He received an intra‐vitreous injection of bevacizumab followed by photodynamic therapy (PDT). The RPED was resolved; however, the VA dropped to 2/60. Optical coherent tomography, fluorescein angiography and indocyanine green angiography were used to indentify retinal angiomatous proliferation. Intra‐vitreal injection(s) of a double dose (1 mg) of ranibizumab is a worthwhile treatment, as it can stabilise and even improve the VA without significant side effects.     

The Role of Eye Movements During Reading in Patients with Age-Related Macular Degeneration (AMD)

AMD patients often have particular difficulty reading, even when the text is magnified to compensate for reduced visual acuity. This study explores whether reading performance can be explained by eye movement factors. Forty patients with advanced AMD were tested with a high-speed video eye tracker to evaluate fixation stability and saccadic eye movements. Reading speed was measured for standardized texts viewed at the critical print size. Visual acuity and contrast sensitivity were unrelated to reading speed, but fixation stability, proportion of regressive saccades and size of forward saccades were all significantly associated with reading performance, accounting for 74% of the variance. The implications of these findings for low-vision training programmes are discussed.     

Effect of viagra on retinal vein diameter in AMD patients

The aim of the present study was to investigate the effect of sildenafil citrate (viagra) on retinal venous diameter in patients with age-related macular degeneration (AMD). We investigated 14 male patients in a double-masked, randomized, placebo-controlled, crossover study. In each subject, one eye with typical non-exudative AMD fundus features was studied. Each of the subjects received 100 mg dose of sildenafil or matching placebo on two separate study visits. Monochromatic fundus photographs were obtained in the study eye before dosing and then 30, 90, 180 and 300 min later. Measurements of the diameter of the major retinal veins from digitized negatives were carried out using "Vessel map" static vessel analysis program (IMEDOS GmbH, Weimar, Germany). Statistical analysis of the data comparing the effect of sildenafil and placebo on venous diameters was performed using analysis of variance (ANOVA) for repeated measures. An analysis of variance (ANOVA) comparing the effects of sildenafil citrate and placebo on retinal vein diameters showed a significant interaction between time and treatment (P = 0.03). In comparison to placebo, sildenafil citrate produced a statistically significant vasodilatation of major retinal veins of 4.7% at 90 min (P = 0.004), 5.5% at 180 min (P < 0.0001) and 5.8% at 300 min (P < 0.0001). At 30 min there was a 2.2% difference, which was not statistically significant (P=0.14). Our results suggest that in patients with age-related macular degeneration, sildenafil citrate (viagra) produces a statistically significant vasodilatation of major retinal veins that is similar to what has been reported in normal subjects. Whether this vasodilatation is associated with changes in retinal blood flow needs to be further investigated.