应用光敏剂维速达尔(Visudyne)进行光动力治疗

维速达尔(Visudyne,注射用维替泊芬)(图1)是诺华公司研制的一种来源于卟啉的第二代光敏药物。应用维速达尔的光动力疗法是治疗脉络膜新生血管形成(CNV)的重要进展之一。该产品于1999年12月16日首先在瑞士获得上市许可,2000年4月13日被美国食品和药品管理局(FDA)批准。2005年在中国上市。目前维速达尔已在140多个国家临床应用。     

视网膜静脉阻塞的动物模型

目的：探讨建立猴眼视网膜静脉阻塞模型的方法。方法：应用氩离子激光光凝封闭猕猴视网膜静脉上、下主干，建立视网膜静脉阻塞的模型。对正常猕猴眼底、视网膜静脉激光光凝阻塞后即刻和24小时的眼底分别行眼底彩色照相和荧光素眼底血管照影，并观察视网膜的组织病理学及超微结构改变。结果：视网膜静脉阻塞后即刻见光凝处静脉剧烈收缩变细，血柱变窄以至消失；阻塞后24小时，可见实验动物眼底沿静脉血管分布呈火焰状出血，视网膜严重水肿，尤以后极部为显。其组织病理学和超微结构显示：视网膜组织水肿、增厚，以外丛状层最严重，可达正常的1—2倍，以细胞内水肿为主；胞质内线粒体肿大、内质网轻、中度扩张。结论：单纯激光光凝封闭猴眼视网膜静脉主干可以建立理想的视网膜静脉阻塞的模型。该模型的建立可为视网膜水肿的临床治疗和基础研究提供可能性。     

光化学法诱导兔视网膜静脉阻塞的实验研究

目的应用光化学法建立实验性兔视网膜静脉阻塞（retinal vein occlusion,RVO）模型。方法新西兰白兔10只,静脉注射孟加拉红后,激光照射视网膜静脉诱导兔眼RVO模型。分别于建模后1h、1d、3d行直接眼底镜和眼底荧光血管造影检查（fundus fluorescein angiography,FFA）。3d后摘除实验眼,行组织学检查。结果9只兔眼经光化学法诱导后,直接眼底镜、FFA检查见光凝远端视网膜静脉扩张迂曲、视网膜出血水肿等典型RVO表现;组织学检查证实光凝视网膜静脉有静脉血栓形成。结论应用光化学法能成功建立可复制、稳定的兔RVO模型,应用此动物模型,可进一步探索RVO的药物治疗并评价其疗效。     

视网膜分枝静脉阻塞的光凝和冷凝治疗

应用光凝和联合使用冷凝的方法对２９例视网膜分枝静脉阻塞患者进行了治疗，出院时视力增进者１５例（５２％）、无变化１４例（４８％）。对１７例作了平均２０．５月的随访观察，视力又有６例增进０．２以上，下降者仅１例。在适应症的选择及疗效判定上强调了荧光眼底血管造影的重要性。本文探讨了光凝的方法，联合冷凝的优点和应用国产激光设备在治疗中的一些体会。     

光动力血栓法制作实验性视网膜分支静脉阻塞模型

目的应用光动力血栓法建立实验性视网膜分支静脉阻塞模型。方法12只兔12眼通过静脉内注射孟加拉红,用氪绿激光照射视网膜静脉分支,分别于照射后1h,3、7、15、30d进行眼底观察,荧光素眼底血管造影(FFA)和病理检查。结果12眼均一次造模成功,阻塞点远端静脉充血、迂曲扩张,不同程度视网膜出血和水肿。1d后3眼有视网膜中央静脉阻塞样表现,15d后5眼阻塞血管有不同程度的再通;FFA显示静脉回流障碍伴静脉内暗红色血栓;病理检查证实静脉内血栓形成。结论光动力血栓法能成功建立视网膜静脉阻塞模型并与人视网膜静脉阻塞形成近似。     

视网膜静脉阻塞动物模型的制作

视网膜静脉阻塞是临床上常见的视网膜疾病,常因严重的并发症导致视力下降甚至失明,位于致盲性视网膜血管病的第二位,随着对本病的重视,国内外学者制作数种动物模型,进行病因、病理学和治疗学上的研究。本文综述了视网膜静脉阻塞动物模型制作的现状,其中包括光化学法、激光光凝法、经玻璃体眼内电凝视网膜静脉法、凝血酶静脉滴注法和玻璃体内注入内皮素-1法等;并探讨各种动物模型中,动物来源是否易获得,是否容易饲养,管理;模型制作的可操作性及与人体机能、代谢形态相似性。     

视网膜静脉阻塞动物模型的制作方法

视网膜静脉阻塞(RVO)分为视网膜分支静脉阻塞和视网膜中央静脉阻塞,是以视网膜静脉扩张迂曲、血流瘀滞、出血和水肿为特征的病变,常并发黄斑水肿和新生血管,新生血管型青光眼是其最严重的并发症。视网膜静脉阻塞对视力危害较大,是仅次于糖尿病性视网膜病变的第二大致盲性眼病。目前为止,视网膜静脉阻塞的患病人数增多,但其发病机制尚未完全明了,而且也无长久有效的治疗方法。实验室中动物模型对视网膜静脉阻塞发病机制和治疗方法的研究至关重要,因此本文对视网膜静脉阻塞实验中使用的动物及模型的制作方法做了简要综述,并对各种视网膜静脉阻塞动物模型的优缺点进行讨论。     

猫眼视网膜静脉阻塞模型的建立

目的:建立类似人类视网膜中央静脉阻塞的动物模型.方法:采用光动力法阻塞猫视网膜3支主干静脉建立模型,建模前、建模后1,3,7,14,28d行眼底照相和荧光素眼底血管造影(fundus fluorescein angiography,FFA)检查.结果:成功建立并观察视网膜静脉阻塞眼42只.建模后1～3 d,视网膜静脉迂曲扩张、出血水肿加重,静脉充盈延迟,毛细血管扩张渗漏,7～14 d部分模型伴随血管再通或侧枝血管形成,上述表现减轻较快,至28d所有模型阻塞静脉均再通,视网膜仍留有色素紊乱,动静脉管径变细不规则,有的可见大片毛细血管无灌注区.结论:采用光动力法阻塞猫视网膜3支主干静脉建立的模型近似模拟了人类视网膜中央静脉阻塞的发展过程.     

Verteporfin photodynamic therapy for anterior segment neovascularization secondary to ischaemic central retinal vein occlusion

Purpose: To evaluate the efficacy of photodynamic therapy (PDT) with verteporfin for anterior segment neovascularizations (ASNVs) in patients affected by ischaemic form of central retinal vein occlusion (CRVO). Methods: Prospective non‐comparative case series including 10 consecutive patients (10 eyes) affected by ischaemic CRVO. Main outcome measure was the obliteration of ASNV. Results: One month after PDT, biomicroscopic examination showed partial obliteration of iris new vessels and complete closure of angle neovascularization. Iris fluorescein angiography performed 1 week after treatment showed partial closure of the iris new vessels with no evidence of leakage in the late phases. During the subsequent examinations, a partial reopening of the iris and angle new vessels in association with dye leakage on fluorescein angiography was evident. In any case, the fluorescein leakage turned out to be still reduced with respect to the baseline aspects. Conclusions: Our results show that PDT with verteporfin can partially obliterate ASNVs in eyes affected by ischaemic CRVO preventing from the evolution towards advanced stages of neovascular glaucoma, but is not effective in cases with complete angle synechial closure.     

应用光动力学方法制作实验性视网膜静脉阻塞模型

目的 应用光动力学方法制备实验性视网膜静脉阻塞模型,以观察眼底形态学和病理学改变。方法 取小型猪15只,随机取单眼为实验组,静脉推入孟加拉玫红(20mg／kg),1min后采用玻璃体切割机眼内照明的导光纤维直接照射视盘上方0．5～1．0PD的视网膜主干静脉15min;分别于血栓形成后1h、3d、7d、14d、21d及28d进行间接眼底镜观察、荧光素眼底血管造影检查,取静脉阻塞区视网膜及血管行光镜和透射电子显微镜观察。对照组对侧眼不注射盂加拉玫红,直接用光导纤维照射靶血管20min,取出光导纤维,缝合切口。分别于光导纤维照射后1h、24h、3d后观察眼底改变,同时摘除眼球,行光镜及电镜观察。结果 视网膜静脉血栓形成可靠,可见视网膜静脉纡曲扩张、广泛出血及水肿等典型病理改变。结论 利用导光纤维眼内照明技术与化学光敏剂方法制作的实验性视网膜静脉阻塞模型,是一种操作简单、定位准确、血栓形成可靠的实验技术。     

半剂量维替泊芬光动力疗法治疗慢性CSCR的回顾性研究

目的：探讨半剂量维替泊芬光动力疗法(photodynamic therapy,PDT)对慢性中心性浆液性脉络膜视网膜病变(central serous chororetinopathy,CSCR)的治疗效果。

方法：病例回顾研究。选择14例19眼已确诊的CSCR患者,所有患者均行Snellen视力表最佳矫正视力(best corrected visual acuity,BCVA)、直接检眼镜眼底检查、荧光素眼底血管造影(fundus fluorescein angiography,FFA)和光相干断层扫描(optical coherence tomography,OCT)检查。病程6～12mo,进行半剂量维替泊芬PDT治疗。治疗后随访6～12mo,观察患者病变区结构和功能改变。对患者治疗前后BCVA和黄斑中心凹区视网膜厚度(central foveal thickness,CFT)进行比较,采用配对t检验。

结果：患者14例19眼经PDT治疗后末次随访时BCVA为0.57±0.08,与治疗前BCVA比较,差异有显著统计学意义(t=2.110,P<0.01)。末次随访时的BCVA与治疗前相比,19眼中有17眼(89.5%)视力改善,2眼(10.5%)视力不变。患者治疗后末次随访时CFT为228.44±56.88μm,与治疗前(368.67±32.18μm)比较,差异有显著统计学意义(t=2.110,P<0.01)。末次随访时OCT检查显示视网膜下液完全吸收17眼(89.5%),部分吸收者2眼(10.5%),随访期间病变无复发。

结论：半剂量维替泊芬光动力疗法对慢性CSCR患者的治疗安全有效。     

Bilateral retinal venous occlusion in pigmentary glaucoma

Background The association of central retinal vein occlusion with primary open angle glaucoma is well known. This communication reports the occurrence of branch retinal vein occlusion and central retinal vein occlusion in a case of pigmentary glaucoma.Methods A 32-year-old man presented with old branch retinal vein occlusion in one eye and resolving central retinal vein occlusion in the other eye. Examination revealed bilateral Krukenbergs spindle and hyperpigmented trabecular meshwork. Intraocular pressure was 30 mmHg OU. Topical antiglaucoma medication was prescribed.Results Intraocular pressure was controlled with topical antiglaucoma medication.Conclusion The present report suggests that intraocular pressure monitoring is important in eyes even with branch retinal vein occlusion. Pigment dispersion may be the underlying cause for bilateral retinal vein occlusion, especially in young patients.     

Photodynamic therapy with verteporfin to induce regression of aggressive retinal astrocytomas

Purpose: To evaluate the effect of photodynamic therapy (PDT) with verteporfin on symptomatic, aggressive retinal astrocytomas. Methods: A prospective, interventional study in a tertiary referral centre. Two patients were treated with a single session of PDT using the standard parameters of the Verteporfin in Photodynamic Therapy (VIP) study: a 34‐year‐old man whose previously stationary juxtapapillary retinal astrocytoma, secondary to tuberous sclerosis, progressed within 7 months to involve the foveola; and a 68‐year‐old man whose acquired retinal astrocytoma progressed over 18 months in spite of standard photocoagulation. Both tumours were vascularized and had caused secondary lipid exudation and an exudative retinal detachment. Outcome measures were visual acuity, resorption of subretinal fluid, tumour height and fluorescein angiography. Results: The progressing, vascularized part of both retinal astrocytomas regressed, with little change in the poorly vascularized, stationary part of the congenital hamartoma. Visual acuity improved in the first patient and was unchanged in the second by 3 months, with stable vision in both and no sign of recurrence at 2 years. The exudative retinal detachments resolved completely. Tumour height reduced a median of 30%. Regression was associated with obliteration of tumour vessels within the progressing part of the lesion, with closure of some of the dilated retinal capillaries over the tumour. Intraretinal microvascular abnormalities and scattered haemorrhages appeared outside the treated area in the first patient. Conclusion: PDT with verteporfin can induce regression of progressive, vascularized, aggressive retinal astrocytomas and may prevent typical progression to total retinal detachment and enucleation, whether the astrocytoma is associated with tuberous sclerosis or not. PDT may be considered a first‐line treatment for aggressive retinal astrocytomas.     

Natural course of experimental retinal vein occlusion in rabbit; arterial occlusion following venous photothrombosis

BACKGROUND: Retinal vein occlusion (RVO) is the second leading cause of vascular eye disease. Currently there is no definite treatment for this condition. Animal models could be potentially helpful in developing new treatments; however, it is essential to understand the differences these models may have with human RVO. The aim of our study was to examine the course of experimentally created retinal vein occlusion (RVO) in rabbits. METHODS: Twenty-nine pigmented rabbits were included in the study. RVO was created in all using an argon green laser following intravenous injection of Rose Bengal. A laser was applied to all major veins at the optic disc margin to mimic central retinal vein occlusion. Animals were followed-up for a maximum of 2 months. RESULTS: Immediately following laser application, blood flow ceased or the flow was extremely slow in the retinal veins in all cases. At day 2 post laser, 86% showed significant retinal hemorrhages. On FA, no retinal blood flow was observed in the eye (neither arteries nor veins) in the majority of rabbits. Between weeks 1 and 3, laser sites reopened and partial or complete revascularization of both retinal arteries and veins occurred; however, the vascular pattern was abnormal. CONCLUSIONS: RVO in rabbits has a different course than in human and it can be classified into three stages. At stage 1 (the first few days after laser photothrombosis), there is a retrograde propagation of the blood clot in the retinal veins that extends to the retinal arteries and choriocapillaries. As a result, there is no retinal blood flow at this stage in most cases. At stage 2 (between weeks 1 and 3), partial or complete revascularization occurs but the vessels have an abnormal pattern. At stage 3 (after week 3) no significant change takes place.     

半剂量维替泊芬与半能量光动力疗法治疗慢性中心性浆液性脉络膜视网膜病变

目的 比较半剂量维替泊芬光动力与半能量光动力疗法(photodynamic therapy,PDT)对慢性中心性浆液性脉络膜视网膜病变(central serous chorioretinopathy,CSC)治疗的有效性和安全性.方法 回顾性队列病例研究.将我院门诊确诊为慢性CSC患者42例(42眼)纳入研究.根据患者PDT治疗过程中所接受的药物剂量和激光参数的不同分为半剂量和半能量组.半剂量组22例(22眼)接受半剂量维替泊芬(3 mg· m-2)和标准能量PDT(83 s,50 J·cm-2)治疗.半能量组20例(20眼)接受全剂量维替泊芬(6 mg·m-2)和半能量PDT (42 s,25 J·cm-2)治疗.PDT治疗后1、3、6个月随访,观察两组患者视网膜下液(subretinal fluid,SRF)完全吸收的比例,最佳矫正视力(best corrected visual acuity,BCVA)变化和黄斑部视网膜厚度(central macular thickness,CMT)的变化.结果 治疗后6个月,半剂量组患者22眼(100％) SRF完全吸收,半能量患者19例(95％)SRF完全吸收,两组间治愈率比较差异无统计学意义(P＞0.05);治疗后6个月,半剂量组BCVA提高7.2字母,半能量组BCVA提高6.7个字母,BCVA提高字母数两组间比较差异无统计学意义(P＞0.05).治疗前半剂量组CMT为(351±90) μm,治疗后6个月降至(178±55) μm,治疗前后比较差异有统计学意义(P＜0.05),半能量组CMT治疗前为(322±96) μm,治疗后6个月降至(181±47) μm,治疗前后比较差异有统计学意义(P＜0.05).所有患者均未出现视网膜色素上皮萎缩、脉络膜新生血管形成等并发症.结论 半剂量维替泊芬光动力和PDT治疗慢性CSC同样安全有效.