Circulating hematopoietic stem cells in patients with neovascular age-related macular degeneration

PURPOSE: Circulating hematopoietic stem cells (HSCs) appear to have roles in the formation of choroidal neovascularization (CNV) in age-related macular degeneration (AMD). This study was conducted to investigate whether the number or function of HSCs plays a role in neovascular AMD. METHODS: Eighty-one patients with neovascular AMD who underwent comprehensive fundus examinations every 3 months were included. The number of CD34(+) HSCs isolated from peripheral blood was counted by flow cytometry. Serum cytokine levels were assessed by enzyme-linked immunosorbent assay. To examine the function of circulating HSCs, mononuclear cells were cultured and then colony forming unit (CFU-EC) and migration were measured. RESULTS: The number of circulating CD34(+) HSCs was significantly increased in the patients with active CNV without major systemic diseases (stable: 3.8 +/- 0.3 cells/microL, active: 5.5 +/- 0.7 cells/microL, stable versus active: P < 0.05). The number of HSCs correlated positively with the erythropoietin serum level (r = 0.47, P = 0.002). Although there was no significant difference in the CFU-EC between the patients with CNV and the control subjects, a significant decrease of CFU-EC was observed in the patients with bilateral or larger CNV. CONCLUSIONS: The findings suggest that CD34(+) HSCs may be recruited from bone marrow through a signal from active CNV. Furthermore, HSCs may play a role in the severity of CNV.     

特发性脉络膜新生血管的治疗

脉络膜新生血管(choroidal neovascularization,CNV)是导致年龄＜50岁的眼病患者中心视力丧失的常见原因,其病因多种多样,常见病因包括病理性近视、特发性CNV(idiopathic choroidal neovascularization,ICNV)、眼拟组织包浆茵病综合征、眼底血管样条纹以及外伤等.其中,年龄＜50岁的CNV患者不伴有明显的眼内炎症反应或存在其他促使新生血管发生的因素,则将此类CNV称为ICNV.ICNV的常见症状包括视物模糊、视物变形、视野固定暗点等.虽然多数患者的自然预后相对良好,但较大面积的CNV常导致中心视力丧失,会严重影响患者生活质量,有必要对其进行及时治疗.目前ICNV的治疗方法包括光动力疗法、抗血管内皮生长因子治疗、激光光凝治疗、手术治疗、经瞳孔温热疗法以及联合治疗等,其中主要治疗方法为光动力疗法和抗血管内皮生长因子治疗.光动力疗法联合皮质类固醇类药物治疗是一种极具前景的治疗方法;对旁中心凹ICNV亦可以考虑进行激光光凝治疗.本文将就ICNV的各项治疗方法做一综述,以期对临床工作有所裨益.     

康柏西普玻璃体内注射治疗特发性脉络膜新生血管

目的探究康柏西普玻璃体内注射治疗特发性脉络膜新生血管(idiopathic choroidal neovascularization,ICNV)的疗效。方法选择2016年1月至2018年1月我院眼科收治的ICNV患者146例(146眼)纳入研究,所有患者均行玻璃体内注射康柏西普治疗,测量治疗前后最佳矫正视力(BCVA)、眼压、黄斑中心凹脉络膜厚度(subfoveal choroidal thickness,SFCT)及上侧脉络膜厚度(superior choroidal thickness,SCT)、下侧脉络膜厚度(inferior choroidal thickness,ICT)、鼻侧脉络膜厚度(nasal choroidal thickness,NCT)、颞侧脉络膜厚度(temporal choroidal thickness,TCT),观察并评价脉络膜新生血管(CNV)渗漏情况,比较患眼治疗前后BCVA、眼压及各区域脉络膜厚度,以及患眼及对侧眼脉络膜厚度差异。结果与治疗前比较,患眼治疗后1 d、1个月时BCVA均显著提高(均为P<0.05)。患眼治疗前后眼压比较差异均无统计...     

玻璃体腔注射Avastin治疗特发性脉络膜新生血管的临床观察

目的 观察玻璃体腔沣射Avastin治疗特发性脉络膜新生血管的临床疗效和安全性.方法 对玻璃体腔注射Avastin治疗特发性脉络膜新生血管16例16只跟进行回顾分析.对比分析治疗前后LogMAR最佳矫正视力(Best corrected visual acuity,BCVA)、光学相干断层扫描(optical coherence tomography ,OCT)、吲哚青绿血管造影(indocyanine green angiography,ICGA)等检查结果.在随访中如有复发者给予重复注药.结果 16例年龄25～42岁,平均(34.50±5.00)岁,随访8～96周,平均(51.50±27.29)周.术前BCVAO～1.69(0.59±0.44),所有病例视力在术后一周时开始提高,4周后趋于稳定,末次随访视力提高1行者1例(6%),3行2例(13%),6行以上者12例(75%),视力无提高但症状改善者1例(6%).术前OCT检查黄斑中心厚度(mean central retinal thickness,CMT)为160～455(291.33±91.72)μm,术后1、2、4、8周及末次CMT分别为152～396(259.67±78.07)μm、123～365(210.50±72.73)μm、1 15～333(167.17±57.56)μm、109～333(151.50±60.13)μm、101～337(150.67±61.95)μm.所有病例在术后一周黄斑区水肿、出血明显消失;治疗后第2个月复查ICGA显示脉络膜新生血管均静止.本组有3例因脉络膜新生血管(CNV)复发,予光动力疗法,并蓖复注射Avastin 1次,其余13例随访期间未见CNV复发.注药前后眼压变化无统计学意义.随访中无全身和眼部并发症发生.结论 玻璃体腔注射Avastin治疗能使脉络膜新生血管迅速消退,较快地提高视力,明显缩短病程,改善预后,且无严重并发症.但其长期疗效和并发症仍需进一步观察.     

玻璃体腔注射Bevacizumab治疗特发性脉络膜新生血管

目的探讨玻璃体腔注射贝伐单抗(Bevacizumab,Avastin)治疗特发性脉络膜新生血管(idiopathic choroidal neovascu-larization,ICNV)的疗效及安全性。方法对32例(32眼)ICNV患者行玻璃体腔注射Avastin1.25mg(0.05mL)。根据复查裂隙灯、眼底检查、光学相干断层扫描、眼底荧光素血管造影(fluorescence fundus angiography,FFA)及最佳矫正视力(best-correctedvisual acuity,BCVA)情况决定是否重复注射。对比观察治疗前后BCVA、黄斑中心凹厚度、眼压及FFA改变情况。结果治疗前BCVA为0.309±0.244,治疗2周后及末次复查时BCVA分别为0.477±0.223、0.670±0.245,差异有显著统计学意义(P<0.001);治疗前黄斑中心凹厚度为(383.280±110.797)μm,治疗2周后及末次复查分别为(296.360±87.850)μm、(264.000±82.978)μm,差异有显著统计学意义(P<0.001);治疗前FFA显示有CNV及荧光渗漏,治疗后新生血管萎缩,无荧光渗漏;治疗前后眼压差异无统计学意义(P>0.05),未发生眼内炎。结论 Avastin是一种安全、有效治疗ICNV的药物。     

特发性脉络膜新生血管患者血清相关因子研究

目的　观察特发性脉络膜新生血管（CNV）患者血清相关因子水平的改变。方法　回顾分析临床确诊为特发性CNV的21例患者21只眼（CNV组）的临床资料。选取20名正常志愿者20只眼作为正常对照组。分别抽取两组受试者静脉血,采用酶联免疫吸附剂测定法和免疫散射比浊法测定血清的血管内皮生长因子（VEGF）,肿瘤坏死因子α（TNFα）,白介素1-β（IL1-β）,免疫球蛋白IgG、IgA、IgM、IgE,总补体CH₅₀、补体C₃、C₄,C反应蛋白（CRP）的浓度。结果　 CNV组血清VEGF浓度显著高于正常对照组(t=2.340,P=0.025),IgE浓度显著低于正常对照组(Z=-2.765,P=0.006);其余血清因子浓度与正常对照组相比,差异均无统计学意义（P＞0.05）。结论　VEGF和IgE可能参与了特发性CNV的形成。     

特发性脉络膜新生血管采用光动力疗法后视网膜色素上皮损伤的研究

目的探讨特发性脉络膜新生血管（CNV）采用光动力疗法（PDT）后视网膜色素上皮（RPE）损伤的原因。方法对43例（45只眼）接受PDT治疗的特发性CNV患者资料进行回顾性分析,以25例（27只眼）CNV膜大小接近的病理性近视合并CNV患者作为对照。分析治疗后4周的荧光素眼底血管造影图像,判断病灶周围色素上皮的透见荧光情况,探讨治疗后8-12周CNV患者的复发原因。结果特发性CNV患者经初次治疗后,PDT光照区内有21只眼的RPE发生改变,二次治疗后又增加了1只眼,RPE改变的发生率约为48．9％,而病理性近视组仅2只眼经PDT治疗后RPE发生改变。随访期内4例特发性CNV患者经PDT治疗后CNV明显扩大。两组CNV患者男女比例基本相同,其男女RPE改变的发生率差异也无统计学意义（P〉0．05）。与病理性近视的CNV患者相比,特发性CNV患者的发病年龄较轻,而病理性近视的CNV患者经治疗后出现RPE改变的2例患者中,1例为37岁,1例为15岁。结论特发性CNV患者经PDT治疗后病灶周围出现RPE损伤,提示年轻患者易出现治疗后的过度反应。     

Indocyanine green angiographic findings in idiopathic choroidal neovascularization

Purpose. Evaluation of choroidal alterations associated with idiopathic choroidal neovascularization (ICNV) and the possible relation between this affection and Multifocal Choroidopathies (MC). Methods. The authors analysed, using high definition videoangiography, the choroidal findings in 21 consecutive patients affected by ICNV (7 males and 14 females; 19–46 years; mean age: 31.8 years); with a follow-up at 5–30 months (mean 13 months). Moreover, a retrospective study of 20 cases of ICNV (11 males and 9 females; age: 17–39 years; mean age: 29.3 years), with a follow-up at 6–11 years (mean 8.9), was performed. Results. In 7 eyes, the indocyanine green angiography (ICGA) showed choroidal hypofluorescent spots similar to those observed in MC (in 3 cases even in the fellow unaffected eye), in 2 of them the regression of the spots was observed after steroid therapy. In 2 eyes, the ICGA revealed hyperfluorescent spots; in one of them the complete regression of the spots after oral cyprofloxacine was observed. In 6 patients (10 eyes), choroidal permeability alterations could be visualized (in 4 cases even in the unaffected eye). Conclusions. The indocyanine green angiographic findings (hypo and hyperfluorescent spots, choroidal permeability alterations) could support the theory of Gass which considers that ICNV is not idiopathic but secondary to a widespread choroidal inflammatory disease. The similarity of the ICGA alterations in ICNV and MC, the observation that cases of ICNV would become MC in the follow-up, could allow the hypothesis of a close connection between these two affections.     

特发性脉络膜新生血管光动力疗法的疗效观察

目的观察光动力疗法（PDT）对特发性脉络膜新生血管（CNV）的治疗效果。方法对61例（61只眼）经荧光素眼底血管造影（FFA）和吲哚氰绿眼底血管造影（ICGA）确诊的特发性CNV患者行PDT治疗,观察比较治疗前后眼底形态、视力、视网膜厚度、FFA和ICGA图像特征。PDT平均治疗次数为1、2次。随访时间为6～36个月,平均19个月。结果末次随访时,61只眼中,有41只眼视力提高（67.2％）,15只眼视力无明显变化（24.6％）,5只眼视力下降（8.2％）。经治疗后所有患眼黄斑出血及渗出均明显减轻。FFA图像显示38只眼的CNV荧光素渗漏完全消失,CNV闭合或瘢痕形成（62．3％）;4只眼CNV部分闭合（6.6％）,14只眼CNV小部分闭合（23．0％）,5只眼CNV复发（8．2％）。6只眼经1次PDT治疗CNV完全闭合,相干光断层扫描或视网膜厚度检查可见黄斑区神经上皮脱离及视网膜水肿消失,随访时间最长3年,未见CNV复发,视力保持稳定。研究结果经多重线性回归分析,表明治疗效果与年龄有关（t=0．476,P=0．016）,即年龄每提高一岁,治疗后视力平均下降0．008（95％CI为0．002～0．015）。结论PDT对特发性CNV有较好的治疗效果,特别对年轻患者效果更好些。（中华腰科杂志,2007,43：509-513）     

玻璃体腔注射Bevacizumab治疗特发性脉络膜新生血管的临床观察

目的观察玻璃体腔注射Bevacizumab治疗特发性脉络膜新生血管的临床效果。方法采用非随机对照临床回顾性研究,对经直接或间接检眼镜、荧光素眼底血管造影和吲哚青绿脉络膜血管造影以及光学相干断层扫描检查确诊的特发性脉络膜新生血管患者共32例(32眼),病程10d～1a,行玻璃体腔注射25g.L-1Bevacizumab治疗,注射次数为1～3次,间隔4周,治疗后随访4～18个月,对比分析术前与末次随访的视力、眼底、荧光素眼底血管造影和吲哚青绿脉络膜造影检查显示的渗漏以及光学相干断层扫描检查显示的平均中央视网膜厚度的变化。结果术前和末次随访时平均logMAR视力分别为0.23590±0.19751和0.39750±0.27287,治疗前后比较差异有显著统计学意义(t=-5.530,P<0.001)。OCT显示术前平均中央视网膜厚度为(317.72±75.01)μm,末次随访为(206.28±31.56)μm,治疗前后比较差异有显著统计学意义(t=8.857,P<0.001)。造影显示渗漏消失者18眼,减少者12眼,渗漏持续者2眼。随访期间有5眼出现小片结膜下出血,1眼出现少量玻璃体腔出血,注射后第2天3眼眼压有明显下降,未见其他并发症。2例病情复发,复发率为6.25%,复发病例进行再次注射治疗仍有疗效。结论玻璃体腔注射Bevacizumab治疗特发性脉络膜新生血管安全有效,但其长期的疗效和安全性评价尚需进行多中心、大样本的临床随机对照研究。     

Transpupillary thermotherapy for idiopathic subfoveal choroidal neovascularization

PURPOSE: To assess the efficacy of transpupillary thermotherapy (TTT) for the management of idiopathic subfoveal choroidal neovascularization (CNV). METHODS: This was a prospective, non-controlled, clinical case trial involving 21 eyes of 21 patients with a mean age of 36 years. All 21 eyes had idiopathic subfoveal CNV and were subjected to diode laser TTT. Laser beam size ranged from 1.2 mm to 3.0 mm and power settings ranged between 300 mW and 600 mW. The end-point was an area of no visible colour change. Pre- and post-laser evaluations of ETDRS visual acuity, contrast sensitivity, slit-lamp biomicroscopy and fluorescein angiography were carried out. RESULTS: The nine predominantly occult and 12 predominantly classic subfoveal membranes were followed-up for a mean of 5.1 months after TTT. Overall, 17 eyes (81%) showed improvement or stabilization in ETDRS visual acuity. Contrast sensitivity improved in 17 eyes (81%). Reading speed improved in 15 eyes (71%). Retreatment was needed in three eyes (14%). CONCLUSION: Transpupillary thermotherapy treatment is a potential strategy for treating idiopathic subfoveal CNV in both its classic and occult forms.     

The role of adult bone marrow-derived stem cells in choroidal neovascularization

PURPOSE: Age-related macular degeneration (ARMD) is the primary cause of blindness in people aged of 50 years or more. The wet form leads to severe loss of central vision. Recent evidence supports that adult hematopoietic stem cells (HSCs) contribute to preretinal neovascularization. In the current study, it was determined whether HSCs, by producing both blood and blood vessels, provide functional hemangioblast activity during choroidal neovascularization (CNV) in mice. METHODS: Gfp chimeric mice were developed by bone marrow ablation of C57BL/6J mice and reconstitution with donor tissue from gfp(+/+) transgenic mice. Gfp chimeric mice underwent laser rupture of Bruch's membrane and were killed and eyes enucleated at 1, 2, 3, and 4 weeks after laser injury. CNV was examined by confocal microscopy of retinal flatmounts. Because endothelial progenitor cells (EPCs) derive from HSCs, immunocytochemistry was used to quantify relative the EPC contribution to CNV. RESULTS: Laser injury alone was sufficient to induce stem cell recruitment and subsequent CNV. Gfp+ cells formed part of the functional vasculature in the choroid as early as 1 week after injury and were present for the duration of the study. The relative EPC contribution to CNV remained fairly constant throughout the study and constituted almost 50% of the total vasculature. CONCLUSIONS: Adult stem cells are recruited to the choroid in a model of CNV, where they contribute to forming aberrant new vessels. This observation suggests that targeting stem cell recruitment to the eye may offer a novel therapeutic strategy for ARMD.     

玻璃体内注射雷珠单抗治疗特发性脉络膜新生血管疗效观察

目的　观察雷珠单抗治疗特发性脉络膜新生血管（ｉｄｉｏｐａｔｈｉｃｃｈｏｒｏｉｄａｌｎｅｏｖａｓｃｕｌａｒｉｚａｔｉｏｎ,ＩＣＮＶ）的有效性和安全性。方法　采用非随机对照临床回顾性研究,对１８例１８眼经间接眼底镜、光学相干断层扫描（ｏｐｔｉｃａｌｃｏｈｅｒｅｎｃｅｔｏｍｏｇｒａｐｈ,ＯＣＴ）、眼底荧光血管造影（ｆｕｎｄｕｓｆｌｕｏｒｅｓｃｅｉｎａｎｇｉｏｇｒａｐｈ,ＦＦＡ）检查确诊的ＩＣＮＶ患者,行玻璃体内注射０．５ｍｇ雷珠单抗治疗。术后每个月随访１次,６个月后若病情稳定可改为每２个月随访一次,随访时经ＯＣＴ、ＦＦＡ证实病情反复者则眼内重复注射。统计分析治疗期间的最佳矫正视力（ｂｅｓｔｃｏｒｒｅｃｔｅｄｖｉｓｕａｌａｃｕｉｔｙ,ＢＣＶＡ）、黄斑中心凹视网膜厚度（ｃｅｎｔｒａｌｒｅｔｉｎａｔｈｉｃｋｎｅｓｓ,ＣＲＴ）、眼部及全身不良反应。结果　１８例１８眼患者均完成６～１２个月的随访,治疗前患者的ＢＣＶＡ为４５．００±１．００,治疗后１周、１个月、３个月、６个月及末次随访时的ＢＣＶＡ分别为５５．８９±４．２３、６４．２２±９．３５、７３．００±７．４４、７６．１７±６．６２、７３．７２±５．９２,与治疗前比较差异有统计学意义（Ｐ＜０．０５）。治疗前患者的ＣＲＴ为（３３８．４４±３７．８５）μｍ,治疗后１周、１个月、３个月、６个月及末次随访时的ＣＲＴ分别是（２８９．２２±３２．５３）μｍ、（２３７．６７±３２．４５）μｍ、（２１６．０６±２５．１１）μｍ、（２１５．３９±２０．４１）μｍ、（２００．３９±１５．１０）μｍ,与治疗前比较差异有统计学意义（Ｐ＜０．０５）。随访过程中未发现全身不良反应及眼部严重并发症。结论　玻璃体内注射雷珠单抗能快速有效地提高ＩＣＮＶ患者的ＢＣＶＡ,稳定病情,但必要时需重复注射。     

大鼠骨髓间充质干细胞在脉络膜新生血管微环境中的分化

目的研究骨髓间充质干细胞（MSCs）在大鼠脉络膜新生血管（CNV）微环境中的分化。方法将体外培养的BN大鼠MSCs植入经氩激光诱导建立的CNV模型大鼠视网膜下腔,用免疫荧光标记的方法对MSCs进行追踪并观察术后1、2、3、4、5周MSCs在CNV微环境中的分化。结果术后第1周即可见MSCs位于CNV表面,但CD31标记阴性,第2周始可见MSCs在CNV内表达CD31阳性,第5周可见移行于光感受器的MSCs表达视紫红质。结论MSCs植入CNV模型大鼠视网膜下腔后可存活,并可向内皮细胞和光感受器细胞方向分化。     

玻璃体内注射康柏西普治疗特发性脉络膜新生血管

目的　观察玻璃体内注射康柏西普治疗特发性脉络膜新生血管（idiopathic choroidal neovascularization,ICNV）的临床疗效。方法　对2015年6月至2017年10月于我院确诊并行玻璃体内注射0.05 mL（0.5 mg）康柏西普治疗的20例20眼ICNV患者的临床资料进行回顾性分析,所有患者均采用1+PRN治疗策略,第1次随访时间为首次注射后1周,以后每月随访1次,均完成6个月的随访。记录CNV病灶渗漏情况、最佳矫正视力（best corrected visual acuity,BCVA）、黄斑中心凹视网膜厚度（central macular retinal thickness,CRT）、眼部及全身不良反应等。结果　20眼中,玻璃体内注射1～3（1.60±0.68）次,其中注射1次者10眼,注射2次者8眼,注射3次者2眼。治疗前BCVA为（55.15±6.82）个字母数,治疗后1周、1个月、3个月、6个月分别为（61.50±6.16）个字母数、（71.00±5.10）个字母数、（73.90±6.75）个字母数、（77.95±5.12）个字母数,治疗前患者CRT为（342.75±36.39）μm,治疗后1周、1个月、3个月、6个月分别为（301.15±32.16）μm、（231.85±30.25）μm、（240.05±56.99）μm、（229.75±48.18）μm,治疗后各时间点BCVA及CRT与治疗前相比差异均有统计学意义（均为P＜0.05）。随访6个月时,17眼病灶渗漏停止,3眼病灶渗漏面积明显缩小,20眼均未出现新的病灶。所有患眼在随访期间均未发生青光眼、眼内炎、白内障进展、视网膜脱离等眼部严重并发症或全身不良反应。结论　玻璃体内注射康柏西普治疗ICNV安全有效。