红花黄色素注射液联合抗VEGF药物治疗非缺血性视网膜中央静脉阻塞

目的：分析红花黄色素注射液联合抗血管内皮生长因子(VEGF)药物治疗非缺血性视网膜中央静脉阻塞(CRVO)的疗效和安全性。

方法：选取2017-04/2021-12于南昌大学附属眼科医院接受治疗的非缺血性CRVO合并黄斑水肿患者91例91眼,随机分为观察组(47例47眼,采用红花黄色素注射液联合玻璃体腔注射雷珠单抗治疗)和对照组(44例44眼,采用玻璃体腔注射雷珠单抗治疗)。随访11mo,观察两组患者最佳矫正视力(BCVA)和中心凹视网膜厚度(CRT)改善情况,并记录视网膜出血完全吸收、抗VEGF药物注射次数、缺血性CRVO发生情况及全身和眼部并发症发生情况。

结果：治疗后1、2、3、5、7、9、11mo,两组患者BCVA和CRT均较治疗前显著改善,且治疗后3、5、7、9、11mo,观察组患者BCVA和CRT均优于对照组(均P<0.05)。治疗后5、7、9、11mo时,观察组患者视网膜出血完全吸收率均高于对照组(P<0.05)。随访期间,观察组患者抗VEGF药物注射次数明显少于对照组(4.83±1.05次 vs 5.75±1.01次,P<0.05),缺血性CRVO发生率明显低于对照组(21% vs 86%,P<0.05),且两组患者均未出现与治疗相关的全身和眼部并发症。

结论：红花黄色素注射液联合抗VEGF药物是治疗非缺血性CRVO安全有效的方法,可显著改善视力,降低CRT,该治疗方案与抗VEGF药物单药治疗相比可增加视网膜出血完全吸收率、减少抗VEGF药物注射次数、减少缺血性CRVO发生率。     

玻璃体黄斑粘连对抗VEGF药物治疗视网膜分支静脉阻塞疗效的影响

目的：探讨玻璃体黄斑粘连(VMA)对视网膜分支静脉阻塞(BRVO)患者抗VEGF治疗的影响。

方法：回顾性病例研究。选取2017-01/2019-05在我院眼科接受玻璃体腔注射康柏西普治疗的BRVO伴黄斑水肿患者110例110眼,根据初诊时OCT特征,将纳入患者分为存在VMA组(VMA+组,34眼)和无VMA组(VMA-组,76眼)。首次注药后至少定期随访6mo,记录注射次数,检测两组患者最佳矫正视力(BCVA)和黄斑中心凹厚度(CMT),根据OCT扫描结果评估玻璃体黄斑粘附状态及黄斑部玻璃体后脱离(PVD)发生情况。

结果：随访至首次注药后6mo,VMA+组和VMA-组患者平均玻璃体腔注射次数无差异(2.91±1.05次 vs 3.08±1.22次,P=0.915)。首次注药后第6mo时,两组患者BCVA和CMT均显著改善,且VMA+组患者BCVA较VMA-组患者增益更明显\〖-0.20(-0.33,-0.10)LogMAR vs-0.20(-0.30,-0.10)LogMAR,P=0.041\〗,但两组患者CMT变化值无差异(P=0.914)。随访期间,VMA+组患者中3眼基线时为局灶性VMA的患眼均发生黄斑部PVD(100.0%),基线时为广泛性VMA的患者31眼中5眼发生了黄斑部PVD(16.1%),局灶性粘连较广泛性粘连的患者更易发生黄斑部PVD(P=0.009)。

结论：BRVO患者合并VMA时抗VEGF治疗后视力改善的潜力更大,故VMA的存在不妨碍抗VEGF治疗BRVO的疗效。     

Effects of intravitreal triamcinolone acetonide on retinal gene expression in a rat model of central retinal vein occlusion

Purpose  

The aim of this study was to investigate the effects of intravitreal triamcinolone acetonide on the alterations in retinal gene expression in a rat model of central retinal vein occlusion (CRVO).     

慎重应用抗新生血管药物治疗视网膜静脉阻塞继发的黄斑水肿

眼内注射抗新生血管药物治疗视网膜静脉阻塞继发的黄斑水肿是近年来出现的新方法,此类药物的短期疗效已得到肯定,但仍然存在治疗后病情复发、需反复多次注射的缺点.相对于经典的激光光凝疗法而言,尚缺乏有力证据表明药物治疗能带来更好的预后.优化的治疗方案包括改变药物注射频率、激光与药物注射治疗联合应用,可减少眼内注射风险和改善患者预后.如何遵照循证医学原则,更科学地选择治疗方法,最大程度保持或改善患眼视功能,是目前临床医师面临的关键问题,需要进一步研究和探讨.     

Intraocular cytokines in retinal vein occlusion and its relation to the efficiency of anti-vascular endothelial growth factor therapy

Purpose:To analyze the change in the concentration of intraocular cytokines (ICs) in patients with retinal vein occlusion (RVO) before and after intravitreal ranibizumab therapy (IVR), and to find the correlations of IC with clinical activity of RVO and efficiency of treatment.Results:The levels of 11 cytokines (vascular endothelial growth factor [VEGF], receptor antagonist interleukin-1, interleukin-6 [IL-6], IL-8, IL-9, IL-10, IL-12r70, IL-13, IL-15, monocyte chemotactic protein-1 [MCP-1], regulated on activation, normal T expressed and secreted) were significantly (P < 0.05) different compared to control and significantly (P < 0.05) changed after IVR both in central and branch RVO. The patients were divided into two groups: the first -“effective” and the second - “partially effective” therapy. The second group characterized by the higher concentrations of VEGF, IL-8, IL-10, IL-17, and MCP-1 at baseline compared to the first group.Conclusion:The patients with RVO were characterized by the increased levels of VEGF and other pro- and anti-inflammatory cytokines and chemokines. Aqueous concentration of cytokines were different in patients with central and branch RVO and significantly changed after IVR. Insufficient response to IVR was associated with activation of immune-inflammatory processes.     

Real-world outcomes of anti-vascular endothelial growth factor therapy for retinal vascular vein occlusion in Tibet, China

AIM: To evaluate the outcomes of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents for patients with retinal vein occlusion (RVO) related-macular edema (ME) in Tibetan. METHODS: A retrospective, observational, single-center study. The demographic and clinical data of 90 RVO Tibetan patients (93 eyes) treated with either ranibizumab or conbercept in Tibet Autonomous Region People’s Hospital from Jan 2018 to December 2019 were collected. RESULTS: The mean patient age was 56.8±10.6y, 45 (50%) of them were female. The mean living altitude was 3867.8±567.9 m. At the last visit, the best-corrected visual acuity (BCVA) significantly increased (52.2±21.8 letters) in comparison with the baseline (38.2±24.1 letters, P<0.001); while the central retinal thickness (CRT) significantly reduced (245.5±147.6 μm) in comparison with the baseline (504.1±165.2 μm, P<0.001). The 43.0% of the eyes gained ≥15 letters, 60.2% of the eyes gained ≥10 letters, and 78.5% of the eyes gained ≥5 letters. No vision loss was noted in 92.5% of the eyes, 4 eyes lost more than 10 letters during follow-up period. The mean number of injections was 2.4±1.8. No severe ocular or systemic adverse events related to either the drug or injection were noted. CONCLUSION: Anti-VEGF therapy is effective and safe in Tibetan patients for the treatment of RVO related ME.     

Predicting recurrences of macular edema due to branch retinal vein occlusion during anti-vascular endothelial growth factor therapy

Graefe's Archive for Clinical and Experimental Ophthalmology - To determine the predictive factors for recurrent macular edema due to branch retinal vein occlusion (BRVO) during intravitreal...     

玻璃体注射抗VEGF药物对全身VEGF浓度的影响

脉络膜视网膜疾病已经成为影响人类视力的严重问题,血管内皮生长因子(vascular endothelial growth factor, VEGF)的异常表达导致眼底血管通透性增加和新生血管的形成。玻璃体抗VEGF药物注射可快速抑制眼内VEGF水平,有效控制疾病发展,目前抗VEGF治疗已成为眼科广泛应用的治疗手段。然而,研究表明玻璃体内抗VEGF药物进入循环系统后降低血浆VEGF浓度,药物无意义的脱靶效应可能导致全身不良反应。对于高龄患者、患有严重合并症患者、哺乳期妇女、早产儿等特殊人群,应关注多次注射后的全身VEGF抑制。本文通过探讨抗VEGF治疗的药物代谢动力学、全身不良反应、对侧眼效应、对母乳和早产儿的影响,对玻璃体注射抗VEGF药物的全身影响进行综述,以期对临床抗VEGF治疗提供可参考的信息。     

Comparison of anti-vascular endothelial growth factors, laser treatments and a combination of the both for treatment of central retinal vein occlusion

AIM: To compare changes in visual acuity and macular edema in patients with central retinal vein occlusion (CRVO) treated with intravitreal injections of bevacizumab, macular grid photocoagulation combined with pan retinal photocoagulation (PRP), or both (bevacizumab+grid+PRP). METHODS: Our study is a retrospective cohort clinical study that examined patients that suffered from ischemic CRVO with macular edema. Study inclusion criteria were ischemic CRVO with macula edema and the availability of complete medical records for at least 12mo after treatment. Excluded were patients with diabetes or any other retinal disease. We reviewed the medical records of patients treated in one ophthalmology department-comparing changes in visual acuity and macular edema in patients treated with intravitreal injections of bevacizumab vs those that were treated with macular grid photocoagulation and PRP or both. The main outcome measures were the differences in best corrected visual acuity (BCVA) and in macular thickness, as assessed by optical coherence tomography, between the enrollment and the final follow up visits. RESULTS: Sixty-five patients met inclusion criteria. There were no statistically significant differences among the three groups in the mean changes in macular thickness as measured by ocular coherence tomography (131.5±41.2, 108.6±29.2, and 121.1±121.1, P=0.110), or in visual acuity (0.128±0.077, 0.088±0.057, and 0.095±0.065), for intravitreal injections, macular grid photocoagulation+PRP and a combination of the treatments, respectively, P=0.111. The proportions of patients with macular edema after treatment were: 26.1%, 28.6%, and 14.3%, respectively, P=0.499. CONCLUSION: Similar benefit was observed for intravitreal injections, laser photocoagulation, or a combined regimen in the treatment of CRVO. A non-statistically significant trend for reduction in macular edema was observed following combined treatment.     

孕期玻璃体腔注射抗血管内皮生长因子药物治疗研究现状

玻璃体腔注射抗VEGF药物在治疗眼底血管性疾病方面得到广泛应用并取得良好效果。孕早期是胎儿器官生成、血管发育的重要时期。现已有研究证明了VEGF在维持胎儿和胎盘血管系统中的重要作用,其水平缺失及下降会影响胚胎发育,导致流产。鉴于抗VEGF药物可能会对母亲和胎儿造成系统性副作用,因此关于孕期玻璃体腔注药的安全性仍存在较大争议。通过总结分析现有关于孕期使用玻璃体腔注射抗VEGF药物治疗的23例病例报道,有3例患者经贝伐单抗治疗后流产。提示临床对孕期患者使用抗VEGF药物时应谨慎,并应向患者详细说明眼部副作用和全身副作用的可能性,在决定是否在怀孕期间使用药物时,应该考虑暴露的时间与血管发育关键期的关系以及不同药物的全身暴露情况。目前临床缺乏孕期抗VEGF药物使用情况分析的大样本量研究,其安全性仍有待进一步观察分析。     

抗血管内皮生长因子药物治疗对视网膜静脉阻塞黄斑水肿患者视网膜毛细血管影响的研究现状

玻璃体腔注射抗VEGF药物是目前治疗视网膜静脉阻塞(RVO)黄斑水肿的主要手段,其能明显抑制新生血管,减轻水肿,提高患者视力。但VEGF是血管内皮细胞的存活因子,其是否会导致视网膜缺血进展以及是否对视网膜毛细血管产生影响值得临床关注。就目前来看,大多学者认为,从拱环形态改变以及浅层、深层视网膜毛细血管层量化黄斑中心凹无血管区面积、视网膜无灌注区大小及黄斑区视网膜血流密度等方面观察,抗VEGF药物治疗RVO黄斑水肿并不会加重视网膜毛细血管的闭塞。并且,这些指标的变化可能与患者需要治疗的次数、视力预后等有一定的关系。今后随着OCT血管成像的逐渐普及以及抗VEGF药物治疗次数和时间的延长,期待更大样本、更长随访时间的研究深入分析抗VEGF药物治疗对RVO黄斑水肿患者视网膜毛细血管的确切影响。     

Factors affecting compliance to intravitreal anti-vascular endothelial growth factor therapy in Indian patients with retinal vein occlusion,age-related macular degeneration,and diabetic macular edema

Purpose:To evaluate the rate of compliance and the reasons for loss to follow-up in Indian patients with diabetic macular edema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO) being treated with anti-vascular endothelial growth factor (VEGF) therapy.Methods:This was a retrospective single-center study. Patients with DME, AMD, or RVO were eligible if they initiated anti-VEGF therapy between January 2013 and December 2017. Patients'' data were obtained from hospital electronic records, including the number of injections received, visits, details of follow-up, missed appointments, and reasons for loss to follow-up (>365 days).Results:A total of 648 patients were eligible for the study, of which 334 (51.54%) patients were lost to follow-up. Overall, 343 (64.96%) were males and the overall mean (SD) age was 66.40 (7.44) years. A total of 376 (58.0%) patients had a history of diabetes and 364 (56.2%) patients had a history of hypertension. Further, 127 (38.0), 112 (33.5), and 95 (28.4) had DME, AMD, and RVO, respectively and were lost to follow-up. The most commonly reported reason for loss to follow-up was “non-affordability” (n = 120; 41.1%) followed by “no improvement in vision” (n = 83; 28.4%). “No improvement in vision” (42.2%) and “non-affordability” (37.5%) were higher among patients with DME. No association was found in gender- and treatment-wise distribution of reasons for loss to follow-up.Conclusion:The results showed that around half of the patients with DME, AMD, and RVO were lost to follow-up to intravitreal anti-VEGF therapy, and the most common factors were “non-affordability” and “no improvement in vision.”     

Intractable glaucoma following intravitreal triamcinolone in central retinal vein occlusion

PURPOSE: To document secondary glaucoma observed after intravitreal injection of triamcinolone for cystoid macular edema in central retinal vein occlusion. DESIGN: An interventional case series. METHODS: Retrospective study. The setting was a tertiary care referral institute. Nine patients with central retinal vein occlusion and cystoid macular edema received 4.0 mg/0.1 ml of intravitreal triamcinolone acetate injected through the inferior pars plana under topical anesthesia. Baseline intraocular pressures were normal in all, and no patients had glaucoma. RESULTS: Seven of the nine patients had a post-injection rise in intraocular pressures, of which one had intractable secondary glaucoma requiring removal of the depot corticosteroid by pars plana vitrectomy combined with trabeculectomy. Two patients were controlled only by maximal medical therapy. CONCLUSIONS: The occurrence of intractable glaucoma after intravitreal triamcinolone in central retinal vein occlusion is a serious concern and warrants caution in the use of this modality for these patients.     

Comparison of intravitreal anti-vascular endothelial growth factor agents and treatment results in Irvine-Gass syndrome

AIM: To investigate the alleviation of scutellarein (SN) against inner blood-retina-barrier (iBRB) dysfunction in vitro mediated by hyperglycemia-stimulated microglia cells and the engaged mechanism. METHODS: Microglia BV2 cells were treated with D-glucose (25 mmol/L) for the indicated times, and 25 mmol/L mannitol was used as an isotonic contrast. Real-time PCR and Western-blot assay were used to detect cellular mRNA and protein expression. Immunofluorescence staining assay was performed. The dysfunction of iBRB in vitro was detected by using transendothelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC)-conjugated dextran cell permeability assay. RESULTS: SN decreased the activation of microglia BV2 cells, reduced the phosphorylation of extracellular regulated protein kinase (ERK)1/2, the nuclear accumulation of nuclear factor kB (NFkB) and the increased expression of pro-inflammatory cytokines including tumor necrosis factor a (TNFa), interleukin (IL)-6 and IL-1b induced by D-glucose (25 mmol/L) in BV2 cells. The results of TEER and FITC-conjugated dextran cell permeability assay showed that SN attenuated iBRB dysfunction in human retinal endothelial cells (HRECs) or choroid-retinal endothelial RF/6A cells when those cells were treated with TNFa, IL-1b or IL-6, or co-cultured with D-glucose-stimulated microglia cells. Moreover, SN restored the reduced protein expression of tight junctions (TJs) in TNFa-treated HRECs and RF/6A cells. CONCLUSIONS: SN alleviated iBRB dysfunction via directly inhibiting retinal endothelial injury caused by pro-inflammatory cytokines including TNFa, IL-1b or IL-6. SN also reduced the release of TNFa, IL-1b and IL-6 from microglia cells by abrogating hyperglycemia-mediated the activation of microglia cells.