糖尿病性黄斑水肿抗VEGF治疗对视网膜毛细血管影响的研究进展

抗血管内皮生长因子(vascular endothelial growth factor,VEGF)药物对于治疗视网膜疾病,比如渗出性年龄相关性黄斑变性、糖尿病视网膜病变(diabetic retinopathy,DR)、视网膜静脉阻塞具有革命性意义。玻璃体腔内注射抗VEGF药物后能明显减轻黄斑水肿,但同时是否也会破坏视网膜微循环、加快视网膜毛细血管闭塞？本文通过相干光断层扫描血流成像(optical coherence tomography angiography,OCTA)和超广角眼底血管造影(ultra-widefield fluorescein angiography,UWFA)技术观察糖尿病性黄斑水肿(diabetic macular edema,DME)患者抗VEGF治疗对视网膜毛细血管的影响,从黄斑无血管区面积、无灌注区大小及血流密度三方面进行综述。     

糖尿病黄斑水肿对抗VEGF药物治疗的不同反应与糖尿病视网膜病变程度的相关性

目的：通过观察糖尿病黄斑水肿(diabetic macular edema,DME)患者对于玻璃体腔注射抗VEGF治疗的不同反应和糖尿病视网膜病变(diabetic retinopathy,DR)的不同程度之间的相关性,进一步阐释糖尿病黄伴水肿的发病机制和治疗策略。

方法：选择非增生性糖尿病视网膜病变(non proliferative diabetic retinopathy,NPDR)伴发DME的患者27例33眼,增生性糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)伴发DME的患者32例34眼。均给予玻璃体腔注射抗VEGF药雷珠单抗,观察两组患者对该药的不同反应,并进行统计学比较。

结果：分别把患者治疗3、6mo时的最佳矫正视力(best corrected visual acuity,BCVA)和黄斑中心视网膜厚度(central macular thickness,CMT)和治疗前的BCVA、CMT作比较,NPDR组有统计学差异(P<0.05),PDR组无统计学差异(P>0.05)。NPDR组和PDR组比较,3、6mo时的BCVR和CMT均有统计学差异(P<0.05)。

结论：糖尿病视网膜病变的不同程度影响着糖尿病黄斑水肿对抗VEGF治疗的反应。     

Short-term results of intravitreal bevacizumab for macular edema with retinal vein obstruction and diabetic macular edema.

OBJECTIVE: The aim of this study was to identify the short-term effect, safety, and durability of intravitreally injected bevacizumab in patients with macular edema (ME) caused by retinal vein obstruction (RVO) and diabetic macular edema (DME). METHODS: We retrospectively evaluated 39 eyes of 36 patients, 14 with ME caused by RVO and 25 with DME, who received intravitreal bevacizumab (1.25 mg) and were followed up for at least 3 months. Monthly assessments examined safety, best corrected visual acuity with an ETDRS chart (logMAR), and central retinal thickness (CRT) using optical coherence tomography. RESULTS: No significant ocular or systemic side-effects were observed. The follow-up period was 5.4 +/- 1.1 months (mean +/- standard deviation). During follow-up, the mean number of injections was 1.4 +/- 0.5. The baseline mean logMAR was 0.91 +/- 0.51, and the mean CRT was 552.6 +/- 186.7 microm. At 1, 2, and 3 months, the mean logMAR was 0.67 +/- 0.46 (paired t test, P < 0.001), 0.66 +/- 0.46 (P < 0.001), and 0.69 +/- 0.45 (P < 0.001), respectively, and the mean CRT was 323.1 +/- 151.9 mum (P < 0.001), 324.6 +/- 136.9 mum (P < 0.001), and 382.5 +/- 130.4 microm (P < 0.001), respectively. Fourteen (14) of 34 eyes with more than 3 months of follow-up required a second injection at a mean 3.4 +/- 1.0 months after the initial injection. For both ME caused RVO and DME patients, a bevacizumab administration improved logMAR and CRT at each time point through to 6 months, except for logMAR in DME at 1 week (P = 0.081), 5 months (P = 0.130) and 6 months (P = 0.759). CONCLUSIONS: An intravitreal bevacizumab injection for ME caused by RVO and DME was safe and effective for improving visual acuity and reducing CRT.     

玻璃体腔注射抗血管内皮生长因子联合激光光凝治疗糖尿病黄斑水肿

目的：观察糖尿病黄斑水肿采取玻璃体腔注射抗血管内皮生长因子药物联合激光光凝的疗效及安全性。

方法：回顾性分析86例102眼糖尿病黄斑水肿患者临床资料,随机分为2组,对照组采取激光光凝治疗; 观察组于对照组基础上加用璃体腔注射抗血管内皮生长因子治疗：麻醉后行常规消毒铺巾,角膜缘后3.5～4mm进针,缓慢注射康栢西普0.05mL,并压迫、包眼。比较两组疗效,并统计两组不良反应。

结果：治疗后两组视力均改善,且观察组视力情况优于对照组(P<0.05); 治疗后观察组总有效率90.9%,高于对照组76.6%(P<0.05); 两组治疗后黄斑中心视网膜厚度(CRT)、黄斑总体积(TMV)水平均降低,且观察组治疗后CRT、TMV水平均低于对照组(P<0.05); 两组不良反应比较差异无统计学意义(P>0.05)。

结论：糖尿病黄斑水肿采用玻璃体腔注射抗血管内皮生长因子药物联合激光光凝治疗疗效较佳,可降低黄斑中心视网膜厚度、距黄斑中心凹6mm范围内黄斑总体积,且应用安全。     

抗VEGF类药物与曲安奈德玻璃体腔注射治疗视网膜中央静脉阻塞继发黄斑水肿的Meta分析

背景 视网膜中央静脉阻塞(CRVO)是常见的视网膜血管病,黄斑水肿是其常见的并发症及患者视力下降的主要原因,玻璃体腔注射抗血管内皮生长因子(VEGF)类药物及曲安奈德已成为治疗黄斑水肿的重要手段. 目的 系统评价抗VEGF类药物与曲安奈德治疗CRVO并发黄斑水肿的临床疗效. 方法 按照检索策略检索PubMed、Cochrane图书馆、EMbase、中国知网(CNKI)、维普(ViP)和万方数据库,查找关于抗VEGF药物与曲安奈德治疗CRVO并发黄斑水肿的临床对照试验.检索时限均为从建库至2015年9月,按照纳入和排除标准筛选文献、提取数据资料,并对纳入的文献进行质量评价.采用Revman 5.3软件对连续变量进行合并效应量检测.结果 共纳入7篇文献,共包括345例患者348眼患眼.抗VEGF药物组与曲安奈德组术后6个月最佳矫正视力和黄斑中心凹厚度比较差异均无统计学意义[平均差(MD)=-0.03,95％置信区间(CI):-0.11 ～0.05,P=0.52;MD=-15.37,95％ CI:-36.29～5.55,P=0.15],眼压比较差异有统计学意义(MD=-2.73,95％ C1:-3.59 ～-1.86,P＜0.000 01).曲安奈德组中22跟出现晶状体混浊,8眼出现眼压升高.抗VEGF药物组中仅2眼出现晶状体混浊. 结论 中期随访内,玻璃体腔注射抗VEGF类药物与曲安奈德均可提高CRVO并发黄斑水肿患者的最佳矫正视力并减轻黄斑水肿,二者疗效相当,但曲安奈德眼压升高等不良反应的发生率高于抗VEGF类药物.     

玻璃体内注射康柏西普对糖尿病黄斑水肿患者和继发于视网膜静脉阻塞的黄斑水肿患者的疗效差异

目的 探讨玻璃体内注射康柏西普对糖尿病黄斑水肿(DME)患者和继发于视网膜静脉阻塞(RVO)的黄斑水肿患者的疗效差异。方法 回顾性研究。选取2019年8月至2021年12月在苏州市立医院北区眼科行玻璃体内注射康柏西普治疗的DME患者44例63眼记为DME组,另选取采用同样方法进行治疗的继发于RVO的黄斑水肿患者40例40眼记为RVO组。采用国际标准视力表(小数)检查并记录患者最佳矫正视力(BCVA),采用德国海德堡公司OCT仪进行OCT检查,自动测量患者黄斑中心凹1 mm视网膜厚度并以此作为黄斑中心视网膜厚度(CMT)。所有患者玻璃体内均一次性注射0.05 mL康柏西普(成都康弘生物科技有限公司)。对比分析DME组和RVO组患眼基线特征及康柏西普治疗后7 d疗效差异。结果 DME组患眼基线CMT为(484.94±152.89)μm, RVO组为(582.33±241.57)μm, RVO组基线CMT高于DME组,差异有统计学意义(P<0.05)。DME组患眼基线BCVA为0.31±0.20,RVO组为0.29±0.23,差异无统计学意义(P>0.05)。注射后7 d, DM...     

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。     

Effects of macular ischemia on the outcome of intravitreal bevacizumab therapy for diabetic macular edema

PURPOSE: To evaluate the effects of macular ischemia on visual outcomes in patients with diabetic macular edema (DME), after intravitreal bevacizumab injections. METHODS: Data on 59 eyes of 53 consecutive patients treated with intravitreal bevacizumab for DME were retrospectively reviewed. Data from preoperative fluorescein angiography (FA) tests were examined. Patients with an enlarged foveal avascular zone (FAZ), >or=1000 microm, or a broken perifoveal capillary ring at the border of the FAZ, with a distinct area of capillary nonperfusion within one disk diameter of the foveal center in the transit phase of fluorescein angiography, were defined as having macular ischemia. The patients were thus divided into two groups: with or without macular ischemia. Early Treatment Diabetic Retinopathy Study (ETDRS) scores, and foveal thicknesses measured using third generation ocular coherence tomography (OCT), were evaluated at baseline and at 1 month and 3 months after treatment. RESULTS: At 3 months after treatment, the mean visual acuity (VA) score decreased from a baseline VA of 0.52 +/- 0.27 (approximate Snellen equivalent, 20/63) to 0.57 +/- 0.21 (20/80) in the ischemic group. In the nonischemic group, by contrast, the VA improved from 0.66 +/- 0.34 (20/100) at baseline to 0.59 +/- 0.33 (20/80) at 3 months post-treatment. Nine of 18 eyes (50%) in the ischemic group, but only 9 of 41 eyes (21%) in the nonischemic group, experienced visual losses of >or=1 line on the ETDRS chart (P = 0.031, Pearson chi-square test). Four eyes (22%) in the ischemic group, but only 2 eyes (5%) in the nonischemic group, lost >or=3 lines (P = 0.042, Pearson chi-square test). CONCLUSION: Macular ischemia may have a negative effect on short term visual outcomes after intravitreal bevacizumab injections in patients with DME.     

糖皮质激素玻璃体给药在糖尿病黄斑水肿治疗中的应用

糖尿病黄斑水肿主要由于血管通透性的增加、血-视网膜屏障破坏、视网膜内或视网膜下液体的异常积聚,导致患者视力损害。以往主要以激光光凝治疗,但其疗效不确切。研究表明玻璃体注射糖皮质激素可有效治疗各种原因引起的黄斑水肿,糖皮质激素因易进入细胞内与胞浆广泛的激素受体结合,形成各种蛋白质,发挥生物效应,进而稳定血-视网膜屏障。但需注意视网膜毒性效应,引起眼压升高以及白内障发生的可能性。综述了糖皮质激素治疗黄斑水肿的作用机制及其在糖尿病黄斑水肿治疗中的研究进展。     

Subthreshold micropulse laser versus intravitreal anti-VEGF for diabetic macular edema patients with relatively better visual acuity

AIM: To compare the effects of yellow (577 nm) subthreshold micropulse laser (SML) and intravitreal (IV) anti-vascular endothelial growth factor (VEGF) treatment in patients with diabetic macular edema (DME) with relatively better visual acuity [best corrected visual acuity (BCVA) ≤0.15 logMAR]. METHODS: The medical records of 76 eyes of 47 patients underwent IV (0.5 mg) anti-VEGF injection or SML for the DME with relatively better BCVA were reviewed. The IV group received three consecutive monthly IV anti-VEGF injections, then were retreated as needed. The laser treatment group was treated at baseline and 3mo, and then retreated at 6 and 9mo if needed. All participants were followed up for one year. The mean BCVA and mean central macular thickness (CMT) values changes over the follow-up were evaluated. RESULTS: Twenty-four and 23 patients were assigned to the SML and IV subgroups, respectively. The mean number of treatments was 3.64±0.76 in SML group and 5.85±1.38 in IV group (P<0.05). The subgroups were similar with regard to the mean BCVA score at baseline and at the 1st and 3rd months, but the score of SML group was better than that of IV group at the 6th, 9th, and 12th months (P<0.05). The decrease in the mean CMT values from baseline values was higher in SML group at the 6th, 9th, and 12th months (P<0.05). CONCLUSION: Yellow SML treatment is superior to IV anti-VEGF injection in DME patients with relatively better BCVA for increasing visual acuity and decreasing CMT at 6, 9, and 12mo. SML can be a good alternative first-line therapy for DME with BCVA ≤0.15 logMAR.     

Geographic pattern of central retinal sensitivity after intravitreal triamcinolone for diabetic macular edema

Graefe's Archive for Clinical and Experimental Ophthalmology -     

Geographic pattern of central retinal sensitivity after intravitreal triamcinolone for diabetic macular edema

Purpose  

To evaluate the geographic pattern of central retinal sensitivity and its resolution shortly after intravitreal injection of triamcinolone acetonide (IVTA) for diabetic macular edema (DME).     

玻璃体腔内注射抗VEGF药物治疗DME对黄斑区微循环的短期影响

目的：应用光学相干断层血管成像(OCTA)观察康柏西普和阿柏西普治疗糖尿病性黄斑水肿(DME)时,黄斑无血管区面积(FAZ)、形态以及血流密度的短期变化。

方法：选择26例DME患者进行玻璃体腔注射康柏西普或阿柏西普,利用OCTA观察注药前、注药后1、7、30d的FAZ、黄斑无血管弓周长(PERIM)、非圆指数(AI),及中心凹300μm宽度内的血管密度(FD-300)的变化,分析抗VEGF药物对黄斑区微循环的影响。同时观察患者最佳矫正视力(BCVA)和黄斑区中心厚度(CFT),BCVA记录时转换为最小分辨角对数(LogMAR)视力。使用重复测量资料方差分析方法,比较注药前、注药后1、7、30d FAZ、PERIM、AI、FD-300、BCVA、CFT的情况; 采用Bonferroni分析不同时间点差异的两两比较。通过Pearson相关分析用来评估BCVA(LogMAR)的变化与FAZ、CFT相关性。

结果：注射抗VEGF药前FAZ为0.296±0.022mm²,注药后1d检测到FAZ增大到0.339±0.024mm²(P=0.015),术后7、30d FAZ与术前无差异(P=0.084、0.224)。与治疗前比较,术后BCVA有明显变化,CFT下降,抗VEGF治疗有效。PERIM、AI及FD-300在注药前后不同时间差异均不显著(F=2.598,P=0.059; F=0.438,P=0.726; F=0.594,P=0.621)。BCVA(LogMAR)与FAZ、CFT正相关(r=0.273,P=0.005; r=0.200,P=0.042),二者均影响BCVA。

结论：糖尿病性黄斑水肿患者玻璃体腔注射抗VEGF药后1d内FAZ可能短暂变大。注药1wk后FAZ减少,并伴有视力提高。选择适当的OCTA参数能提供可靠的客观测定方法。     

Alterations in central retinal sensitivity after intravitreal triamcinolone injection for diffuse diabetic macular edema

PURPOSE: To evaluate alterations in central retinal sensitivity following intravitreal triamcinolone injection in patients with diffuse diabetic macular edema that persisted after laser treatment. METHODS: Fourteen eyes of 14 patients that received 4 mg 0.1 cc intravitreal triamcinolone underwent macular threshold test using computerized visual field analyzer before and after 1, 2, 3, and 5 months of triamcinolone injection. Pre- and postinjection values of total defect depth, total threshold, and best-corrected visual acuity were compared and correlated. RESULTS: At the last follow-up, compared to baseline, visual acuity improved from 1.4+/-0.4 (logMAR, mean +/- standard deviation) to 1.0+/0.4 (p=0.01). Total defect depth tended to recover from 148+/-64 dB to 121+/-48 dB (p=0.12), and total threshold tended to increase from 241+/-87 dB to 271+/-68 dB (p=0.16), but these values did not reach significance. There was a significant correlation between baseline and 5 months postinjection values of total defect depth (rho=0.60, p=0.02), and of total threshold of light sensitivity (rho=0.55, p=0.04). CONCLUSIONS: Best-corrected visual acuity was found improved in patients with diabetic macular edema 5 months after triamcinolone injection. Improvement in central retinal sensitivity did not reach significant level at the last follow-up. Macular threshold test may be a valuable tool in the follow- up of patients with diffuse diabetic macular edema after intravitreal triamcinolone injection.     

Sequential restoration of external limiting membrane and ellipsoid zone after intravitreal anti-VEGF therapy in diabetic macular oedema

Background/ObjectivesTo study the mechanism of restoration of retinal photoreceptor ellipsoid zone (EZ), after intravitreal bevacizumab (IVB) therapy, in diabetic macular oedema (DMO).Subjects/MethodsForty-four consecutive patients aged 40–65 years having type 2 diabetes mellitus (DM) with DMO were prospectively recruited for IVB therapy. It comprised of three doses (1.25 mg in 0.05 ml) of IVB at monthly intervals. Patients with other ocular and systemic diseases affecting retinal vessels and earlier ophthalmological interventions were excluded. Visual acuity (logMAR VA) was recorded. Spectral domain optical coherence tomography (SD-OCT) was performed pre and post intervention. Central sub-foveal thickness (CST) and grades of disorganization of retinal inner layers (DRIL), external limiting membrane (ELM) and EZ were assessed. Data were statistically analysed on SPSS software. Clinical trials registry: CTRI/2019/03/018135.ResultsMean logMAR VA decreased after IVB therapy from 1.78 ± 0.07 pre-intervention to 0.42 ± 0.05 post intervention (p < 0.001). Similarly, CST reduced from 354.23 ± 15.0 µm pre-intervention to 233.18 ± 7.88 µm post intervention (p < 0.001). Among qualitative variables, DRIL decreased from 93.2% pre-intervention to 13.6% post intervention. Likewise, global ELM disruption reduced from 81.8 to 9.1% and global EZ disruption reduced from 79.5 to 11.4%. ELM restoration preceded EZ restoration.ConclusionAnti-VEGF therapy restores the barrier effect of ELM. It causes ELM to restore first followed by EZ restoration in DMO.Subject terms: Retinal diseases, Tomography, Chemotherapy     

中西医结合治疗糖尿病性黄斑水肿的疗效分析

目的:观察自拟中药益气引水消肿方联合康柏西普及激光治疗糖尿病性黄斑水肿(DME)的临床疗效。方法:选取2016-01/2018-10在我院眼科就诊的DME患者60例60眼,随机分为对照组给予玻璃体腔内注射康柏西普,中西医组在对照组的治疗基础上加用自拟益气引水消肿方,所有患者根据病情行光凝治疗。观察两组患者在治疗前和治疗后1、3、6mo最佳矫正视力(BCVA)、黄斑中心凹厚度(CMT),以及治疗后6mo荧光素眼底血管造影(FFA)中黄斑荧光渗漏情况和黄斑水肿的复发率。结果:对照组治疗前BCVA(LogMAR)为0.92±0.26,治疗后1、3、6mo BCVA分别为0.58±0.18、0.60±0.27、0.62±0.28,中西医组治疗前BCVA(LogMAR)为0.94±0.31,治疗后1、3、6mo BCVA分别为0.56±0.20、0.50±0.25、0.51±0.21;对照组治疗前CMT为461.62±84.26μm,治疗后1、3、6mo CMT为299.92±43.18、290.60±39.36、311.10±42.78μm,中西医组治疗前CMT为455.74±83.89μm,治疗后1、3、6mo CMT分别为288.96±40.20、265.86±32.55、270.38±31.60μm,两组患者在治疗后与治疗前相比BCVA和CMT均有所改善(P<0.05)。在治疗后1mo中西医组与对照组比较BCVA和CMT无差异(t=0.539、0.739,P>0.05),在治疗后3、6mo中西医组BCVA和CMT有明显改善,与对照组相比有差异(t治疗后3mo=2.891、2.992,P治疗后3mo=0.004、0.021;t治疗后6mo=3.733、3.643,P治疗后6mo<0.01、0.005),在治疗后6mo中西医组黄斑水肿复发率更低(χ=4.344,P<0.05)。结论:益气引水消肿方联合康柏西普及激光治疗DME可以改善视力、减轻黄斑水肿、减少水肿复发率。