玻璃体腔单次注射雷珠单抗治疗糖尿病黄斑水肿与视网膜静脉阻塞性黄斑水肿的短期疗效观察

目的评价玻璃体腔单次注射抗血管内皮细胞生长因子药物雷珠单抗治疗糖尿病黄斑水肿DME和视网膜静脉阻塞（RVO）性黄斑水肿的短期疗效。方法在安徽医科大学第一附属医院规律随访符合纳入和排除标准的DME和RVO黄斑水肿者23只眼。患眼给予玻璃体腔注射0.05 ml雷珠单抗注射液,治疗后2 d复查最佳矫正视力,治疗后4周进行复查最佳矫正视力、黄斑中心凹厚度、黄斑区平均厚度和Amsler表。结果治疗后2 d与治疗前相比,视力提高（t=4.632,P〈0.001）。治疗后4周与治疗前相比,黄斑中心凹厚度降低（t=10.165,P〈0.001）,黄斑区平均厚度降低（t=3.368,P=0.003）,视力提高（t=7.281,P〈0.001）。Amsler表阳性率下降（χ2=8.013,P=0.005）。差异均具有统计学意义。治疗后4周与治疗后2 d相比,视力提高,差别有统计学意义（t=5.271,P〈0.001）。黄斑中心凹厚度与Amsler表阳性率的相关性分析：无统计学意义（相关系数0.128,P=0.398）。结论玻璃体腔单次注射雷珠单抗对DME和RVO黄斑水肿在4周内有效。     

玻璃体内注射雷珠单抗治疗变性近视黄斑脉络膜新生血管形成

目的 评价玻璃体内注射雷珠单抗（Ranibizumab）治疗变性近视黄斑脉络膜新生血管形成（CNV）的临床疗效.方法 单中心随机对照临床回顾性研究.并发黄斑CNV的变性近视连续病例34例（36眼）,玻璃体内注射雷珠单抗0.5 mg（0.05 ml）,注射后第1、2、3、6个月各随访1次,并于第1、2个月随访时各追加注射1次.通过最佳矫正视力、裂隙灯显微镜、眼压、检眼镜、眼底彩色照像、光学相关断层扫描（OCT）及荧光素眼底血管造影（FFA）检查,分析治疗前后最佳矫正视力、黄斑视网膜纤维层厚度的变化.结果 术前视力为0.15±0.10,术后6个月为0.25±0.16,差异有统计学意义（t=6.02,P＜0.04）.黄斑视网膜厚度术前为（315.94±13.19） μm,术后为（292.19±20.24） μm,差异有统计学意义（t=7.87,P＜0.01）.FFA显示有22眼渗漏消失,13眼渗漏面积明显减小,1眼发现新鲜出血.结论 玻璃体内注射雷珠单抗治疗变性近视黄斑CNV可使脉络膜新生血管逐渐萎缩,减少出血及渗漏,从而减轻黄斑水肿,提高视力,是目前治疗变性近视黄斑CNV的有效方法之一.     

Topical Ranibizumab inhibits inflammatory corneal hem‐ and lymphangiogenesis

Purpose: Ranibizumab (Lucentis^®) is a Fab‐Fragment of a recombinant, humanized, monoclonal VEGF (anti‐vascular endothelial growth factor) antibody. This study analyzed the ability of topical Ranibizumab to inhibit lymphangiogenesis in addition to hemangiogenesis after acute corneal inflammation in vivo. In addition, the effect of Ranibizumab on the proliferation of human lymphatic endothelial cells (LECs) and blood endothelial cells (BECs) in vitro was studied. Methods: The inhibitory effect of Ranibizumab on LECs and BECs was studied in vitro using a proliferation enzyme‐linked immunosorbent assay (ELISA) assay. To study the in vivo effects of Ranibizumab, the mouse model of suture induced inflammatory corneal neovascularization was used. Study mice received topical Ranibizumab as eye drops. After 1 week excised corneas were stained with LYVE‐1 and CD31. Hemangiogenesis and lymphangiogenesis were analyzed morphometrically by using a semiautomatic method based on the image analyzing program Cell^F. Results: An antiproliferative effect of Ranibizumab was seen in vitro on both human BECs and LECs with a significance of p < 0.0001 and p < 0.0004, respectively. In vivo experiments showed that topical application of Ranibizumab significantly inhibits both hemangiogenesis (p = 0.0026) and lymphangiogenesis (p = 0.0026) in the cornea. Conclusion: Ranibizumab is a potent inhibitor of inflammatory corneal hemangiogenesis and lymphangiogenesis in vivo with a direct inhibitory effect on both endothelial cell types in vitro. This study for the first time demonstrates an inhibitory effect of Ranibizumab on lymphatic vessels which could have a wider range of clinical applications.     

抗VEGF药物治疗葡萄膜炎并发黄斑囊样水肿和脉络膜新生血管研究进展

葡萄膜炎是累及眼后段的炎症性疾病,病程长,对视功能的损害明显,可出现黄斑囊样水肿（CME）、白内障、青光眼、视网膜脱离、脉络膜新生血管（CNV）等多种并发症.在葡萄膜炎的发病和进展过程中,炎性因子通过多种途径影响血管内皮生长因子（VEGF）的释放,研究已证实在并发CME的葡萄膜炎患者玻璃体腔内VEGF含量升高.玻璃体腔内注射抗VEGF药物,如雷珠单抗和贝伐单抗,治疗非感染性葡萄膜炎相关性CME及CNV对于大部分病例有效,且能改善患者的视力,但可能需多次反复注射.对于一些病程长,CME持续存在,或不宜应用糖皮质激素、免疫抑制剂进行治疗的患者,球内注射抗VEGF药物是可选择的有效方法,但这种方式可能对糖皮质激素的疗效产生一定的影响,仍需更多的临床观察与基础研究进一步证实.就应用抗VEGF药物治疗葡萄膜炎并发CME和CNV的研究现状和进展进行综述.     

雷珠单抗治疗重度视力损害渗出型年龄相关性黄斑变性患者的疗效观察

目的观察玻璃体腔注射雷珠单抗治疗重度视力损害渗出型年龄相关性黄斑变性(AMD)患者的疗效。方法回顾性分析在我院确诊为渗出型AMD、最佳矫正视力(BCVA)<0.05并接受雷珠单抗玻璃体腔注射的46例患者(47只眼)的临床资料。所有患者均行玻璃体腔注射雷珠单抗治疗,治疗后随访1~8个月,平均随访(4.09±2.25)个月。对比分析玻璃体腔注射雷珠单抗治疗前后BCVA、黄斑中心视网膜厚度(CRT)、病变最厚处视网膜厚度(MRT)的变化及不良反应的发生情况。结果至末次随访时,47只眼中,视力提高29只眼,占61.7%;视力稳定15只眼,占31.9%;视力下降3只眼,占6.4%。治疗后,平均CRT由治疗前的(301.30±84.57)μm降低为(211.27±87.03)μm;与治疗前相比,平均CRT下降(90.03±33.99)μm,差异有统计学意义(t=4.336,P<0.01);MRT由(529.04±174.63)μm降低为(421.86±95.78)μm;与治疗前相比,平均MRT下降(107.17±42.46)μm,差异有统计学意义(t=3.984,P<0.01)。结论雷珠单抗治疗重度视力损害渗出型AMD患者具有较好的疗效。     

阿柏西普与雷珠单抗治疗糖尿病性黄斑水肿的疗效比较

目的：分析阿柏西普和雷珠单抗对糖尿病性黄斑水肿治疗的疗效。

方法：前瞻性研究。选择2019-11/2020-02于邢台市人民医院眼科首次就诊的糖尿病性黄斑水肿(DME)的患者纳入研究,随机按治疗方式分为阿柏西普组与雷珠单抗组,采用3+PRN(pro re nata)的治疗方案,两次注射时间间隔至少4wk,所有患者均先注射3次,随访时根据患者的最佳矫正视力(BCVA)及黄斑部中心凹视网膜厚度(CFT)的大小决定是否再次注射,患者均完成12mo随访,记录治疗前后两组患者的BCVA、CFT、眼压以及注射次数的变化。

结果：两组患者的BCVA、CFT在术前及术后随访中均有差异(P<0.05),两组间BCVA及CFT随访期间均无差异(P>0.05)。随访结束时,阿柏西普组平均注射次数为6.094±0.689次,雷珠单抗组为7.231±0.652次,比较无差异(t=-6.403,P<0.05)。所有患者均未出现眼部并发症以及全身不良反应。

结论：与玻璃体腔注射雷珠单抗比较,注射阿柏西普注射液治疗DME能取得相似的治疗效果,且注射次数更少。     

Cost-effectiveness sequential modeling of ranibizumab versus usual care in age-related macular degeneration

Aims  To assess effectiveness, cost, and cost-effectiveness of ranibizumab versus the current medical practices of treating age-related macular degeneration in France. Methods  A simulation decision framework over 1 year compared ranibizumab versus the usual care using two effectiveness criteria: the “visual acuity improvement rate” (greater than 15 letters on the ETDRS scale) and the “rate of legal blindness avoided”. Two decision trees included various sequences of current treatments, with or without ranibizumab. Results  Ranibizumab appeared significantly more effective than the usual care (p < 0.001), providing greater treatment success rate of visual acuity improvement (48.8% versus 33.9%). The cost of the ranibizumab strategy was higher (9,123 euros (€) over 1 year for ranibizumab versus 7,604 € for the usual care) but the average cost-effectiveness was lower – 18,721 € /success for ranibizumab versus 22,543 €/success for usual care (p < 0.001). Considering the “legal blindness avoided” success criterion, the ranibizumab strategy appeared significantly more effective (p < 0.001), providing greater treatment success rate for of legal blindness avoided than usual care (99.7% versus 93.1%) although it was more expensive (9,196 € over 1 year for ranibizumab versus 5,713 € for the usual care). Conclusion  Ranibizumab significantly improved the rate of visual acuity improvement and reduced the rate of legal blindness. Ranibizumab appeared significantly more cost-effective than the usual treatments in terms of visual acuity improvement. Financial relationships: This study was sponsored by Novartis Pharma SAS, France. The authors have no financial interests with the sponsor and have full control of all primary data. Thomas Citterio and Ségolène Bisot-Locard are employees of Novartis, France. The authors agree to allow Graefes Archive for Clinical and Experimental Ophthalmology to review their data upon request.     

雷珠单抗治疗新生血管性年龄相关性黄斑变性的长期疗效

目的：研究就诊于我院新生血管性年龄相关性黄斑变性(NV-AMD)患者使用雷珠单抗治疗后3年的疗效。

方法：回顾性研究。共纳入73例(101眼)患者。根据入组时视力情况(ETDRS chart),患者被分为3组。第1组：视力≤ 35; 第2组：视力36～54; 第3组：视力≥55字母。患者接受3次,每次0.5 mg的雷珠单抗负荷剂量,之后根据病情决定是否再次注射。对患者每月进行一次随访,进行视力、详细的眼前节及眼底的生物显微镜,以及光学相干断层扫描(OCT)检查。对最接近12、24、36mo的视力检查结果进行分析。

结果：纳入的101眼中,男性57眼,女性44眼。患者平均年龄75.1岁。治疗24mo和36mo时,三组患者之间视力变化情况差异均有统计学意义(P=0.002, 0.0001)。治疗36mo后,第2组视力较入组时显著改善(P=0.001),第3组患者视力改善不显著。随访12、24、36mo时,第1组视力无明显变化的患者人数最多。所有患者平均注射雷珠单抗7.3次,随访次数23.9次。

结论：入组时视力情况尚可的患者视力改善最明显。视力较差和视力较好的患者视力改变不明显。最终视力与注射次数无明显关系。