4月 | Vesber 最佳RIO论文推荐

学习学习再学习,分享分享再分享!学习使人年轻,学习使人快乐。为给大家提供眼科最新资讯,卫视博将每个月从三大权威杂志:Retina、Investigative Ophthalmology & Visual Science、Ophthalmology中各推荐一篇眼科相关论文,合称“最佳RIO论文推荐”。接下来且看学习心得,且听论文分解▽

Retina · 推荐

《ADVERSE EVENTS OF THE ARGUS II RETINAL PROSTHESIS: Incidence, Causes, and Best Practices for Managing and Preventing Conjunctival Erosion》(Retina. 2020,40(2):303-311.)
《ARGUS II视网膜芯片的不良反应:结膜糜烂的发生率、原因和管理预防的最佳措施》
Purpose:To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients.
目的:分析和综述ArgusⅡ临床试验受试者和批准后患者结膜糜烂的发生率及管理预防。
Methods:This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing.
方法:回顾性分析了2007年6月至2017年11月间274例使用Argus II视网膜修复系统治疗的患者的结果,其中30例来自美国和欧洲临床试验,244例处于批准后阶段。收集严重不良事件发生率、结膜糜烂发生率、发生部位、糜烂率和糜烂时间的结果。
Results:Overall, 60% of subjects in the clinical trial subjects versus 83% of patients in the postapproval phase did not experience device- or surgery-related serious adverse events. In the postapproval phase, conjunctival erosion had an incidence rate of 6.2% over 5 years and 11 months. In 55% of conjunctival erosion cases, erosion occurred in the inferotemporal quadrant, 25% in the superotemporal quadrant, and 20% in both. Sixty percent of the erosion events occurred in the first 15 months after implantation, and 85% within the first 2.5 years.
结果:总的来说,60%的临床试验受试者和83%的批准后阶段的受试者没有发生与器械或手术相关的严重不良事件。术后5年11个月间结膜糜烂发生率为6.2%。55%的结膜糜烂发生在颞下象限,25%发生在颞上象限,20%发生在颞上和颞下。60%的糜烂发生在植入后的前15个月,85%发生在植入后的前2.5年。
Conclusion:Reducing occurrence of conjunctival erosion in patients with the Argus II Retinal Prosthesis requires identification and minimization of risk factors before and during implantation. Implementing inverted sutures at the implant tabs, use of graft material at these locations as well as Mersilene rather than nylon sutures, and accurate Tenon’s and conjunctiva closure are recommended for consideration in all patients.
结论:减少Argus II视网膜芯片患者结膜糜烂的发生需要在植入前和植入过程中识别并最小化危险因素。建议考虑对所有患者在植入片处实施倒转缝合,在这些位置使用和移植物材料一致的美西林线缝合,而不是尼龙线缝合,以及准确的将Tenon’s膜和结膜闭合。
推荐理由:创新产品总是充满困难和挑战,Argus 从I代到 II代,历经十余年的不断探索和改进,虽有一定的并发症,但是仍然给患者带来了光明和希望。这是一篇回顾性分析一种Argus II视网膜芯片在临床试验期及获批后使用情况的研究。入选了长达10年间的包括临床试验和获批后的274例患者数据,重点分析了Argus II视网膜芯片的术后结膜糜烂的发生率,部位与发生时间,及给出了一系列相关预防管理建议。
本文的创新之处在于探索一个获批的临床新产品在后期使用中可能发生的不良事件,并通过大样本统计分析确定该不良事件与新器械产品无相关性。同时针对该不良事件的管理预防给出了一系列改进的建议措施,有效的努力降低该不良事件的发生率。但是该文章的局限性为仅单一的报道了术后结膜糜烂这一种现象。评价每一个临床新产品,往往需要多方数据的全面支撑。在未来的研究中,可以将视力情况,眼压情况,患者排斥情况等等的其他数据情况也纳入分析标准,做一个更加全方位的评价。

IOVS · 推荐

《Angiotensin-(1–7) Attenuates Protein O-GlcNAcylation in the Retina by EPAC/Rap1-Dependent Inhibition of O-GlcNAc Transferase》(Invest Ophthalmol Vis Sci. 2020;61(2):24.)
血管紧张素-(1-7)通过EPAC / Rap1依赖抑制O-乙酰氨基葡萄糖转移酶降低视网膜蛋白 O-乙酰氨基葡萄糖乙酰化的表达
Purpose:O-GlcNAcylation of cellular proteins contributes to the pathophysiology of diabetes and evidence supports a role for augmented O-GlcNAcylation in diabetic retinopathy. The aim of this study was to investigate the impact of the renin-angiotensin system on retinal protein O-GlcNAcylation.
目的: 细胞蛋白的O-乙酰氨基葡萄糖乙酰化有助于了解糖尿病的病理生理,证据支持在糖尿病性视网膜病变中O-乙酰氨基葡萄糖乙酰化的表达增加。这项研究的目的是研究肾素-血管紧张素系统对视网膜蛋白O-乙酰氨基葡萄糖乙酰化的影响。
Methods:Mice fed a high-fat diet were treated chronically with the angiotensinconverting enzyme inhibitor captopril or captopril plus the angiotensin-(1–7) Mas receptor antagonist A779. Western blotting and quantitative polymerase chain reaction were used to analyze retinal homogenates. Similar analyses were performed on lysates from human MIO-M1 retinal Müller cell cultures exposed to media supplemented with angiotensin-(1–7). Culture conditions were manipulated to influence the hexosamine biosynthetic pathway and/or signaling downstream of the Mas receptor.
方法: 饲喂高脂饮食的小鼠长期接受血管紧张素转换酶抑制剂卡托普利或卡托普利加血管紧张素-(1-7)Mas受体拮抗剂A779的治疗。蛋白质印迹和定量聚合酶链反应用于分析视网膜匀浆。对暴露于补充血管紧张素(1-7)-的培养基中的人MIO-M1视网膜Muller细胞裂解物进行了类似的分析。控制培养条件以影响己糖胺的生物合成途径和/或Mas受体下游的信号传导。
Results:In the retina of mice fed a high-fat diet, captopril attenuated protein O-GlcNAcylation in a manner dependent on Mas receptor activation. In MIO-M1 cells, angiotensin-(1–7) or adenylate cyclase activation were sufficient to enhance cyclic AMP (cAMP) levels and inhibit O-GlcNAcylation. The repressive effect of cAMP on OGlcNAcylation was dependent on exchange protein activated by cAMP (EPAC), but not protein kinase A, and was recapitulated by a constitutively active variant of the small GTPase Rap1. We provide evidence that cAMP and angiotensin-(1–7) act to suppress OGlcNAcylation by inhibition of O-GlcNAc transferase (OGT) activity. In cells exposed to an O-GlcNAcase inhibitor or hyperglycemic culture conditions, mitochondrial superoxide levels were elevated; however, angiotensin-(1–7) signaling prevented the effect.
结果:在高脂饮食的小鼠视网膜中,卡托普利以依赖Mas受体激活的方式减弱了蛋白O-乙酰氨基葡萄糖乙酰化。在MIO-M1细胞中,血管紧张素-(1-7)或腺苷酸环化酶激活足以增强环腺苷酸(cAMP)的水平并抑制O-乙酰氨基葡萄糖乙酰化。cAMP对O-乙酰氨基葡萄糖乙酰化的抑制作用取决于cAMP激活的交换蛋白(EPAC),而不取决于蛋白激酶A,并被短三磷酸鸟苷酶 Rap1的组成型活性变构体重构。我们提供的证据表明,cAMP和血管紧张素-(1-7)通过抑制O-乙酰氨基葡萄糖转移酶(OGT)的活性来抑制O-乙酰氨基葡萄糖乙酰化的作用。在暴露于O-乙酰氨基葡萄糖酶抑制剂或高血糖培养条件下的细胞中,线粒体过氧化物水平升高;然而,血管紧张素-(1-7)信号传导阻止了这种作用。
Conclusion:Angiotensin-(1–7) inhibits retinal protein O-GlcNAcylation via an EPAC/Rap1/OGT signaling axis.
结论: 血管紧张素-(1-7)通过EPAC / Rap1 / OGT信号通路抑制视网膜蛋白O-乙酰氨基葡萄糖乙酰化。
推荐理由:这是一篇关于糖尿病性视网膜病(DR)的研究论文,本研究证实了Ang1–7通过调节己糖胺生物合成途径(HBP)减弱视网膜蛋白O-乙酰氨基葡萄糖乙酰化的假说,于2020年发表在IOVS杂志上。
有研究表明,在晶状体,角膜,视网膜色素上皮,神经视网膜和视网膜脉管系统中已经发现了O-乙酰氨基葡萄糖乙酰化蛋白的表达。在这项研究中,作者发现在高脂饮食小鼠的视网膜中,卡托普利减弱了视网膜蛋白 O-乙酰氨基葡萄糖乙酰化,并且通过Mas受体抑制作用阻止了该作用。这一发现提供了新的见解,探讨了Ang1–7水平升高在视网膜抑制ACE的有益作用中的作用。同时,在本研究中,作者认为线粒体功能障碍和ROS产生增加是糖尿病性视网膜病发展的关键。所以,这篇文章提示了我们对于一些糖尿病病或者糖尿病视网膜病变的患者,服用血管紧张素酶抑制剂,可能会有利于患者减缓疾病的发生,减轻患者的痛苦。但本文属于临床前基础研究,尽管在研究中确定了Ang1-7,蛋白O-乙酰氨基葡萄糖乙酰化和视网膜中ROS产生之间的新型分子联系,但其中有部分的机制研究仍不是特别清晰;同时,本研究只进行了动物实验,是否真的可以应用到人身上仍是一个疑问。因此我们需要更多的研究来证明Ang1-7对于治疗糖尿病视网膜病变的作用。
附录:Ang1-7 抑制视网膜蛋白O-乙酰氨基葡萄糖乙酰化的工作模型

Ophthalmology · 推荐

《A Collaborative Retrospective Study on the Efficacy and Safety of Intravitreal Dexamethasone Implant (Ozurdex) in Patients with Diabetic Macular Edema: The European DME Registry Study》(Ophthalmology. 2020;127(3):377-393.)
《糖尿病黄斑水肿患者玻璃体内地塞米松植入物(Ozurdex)疗效和安全性的协作性回顾性研究:欧洲DME注册研究》
Purpose:To evaluate the efficacy, effect profile, and safety of dexamethasone implant on diabetic macular edema (DME) in a real-life setting, further comparing results by DME duration, previous treatment status, and diabetic control.
评估在真实事件中地塞米松植入物对糖尿病性黄斑水肿(DME)的有效性、效应范围和安全性,并进一步比较DME持续时间、既往治疗状态和糖尿病控制的结果。
Methods:Data were analyzed in 2 perspectives: per injection, in which all measurements were grouped and baseline was defined as the day of injection, and thus the pharmacodynamics of single injections could be assessed; and injection series, defined as 2 or more injections with 3 to 6 months between injections analyzing the outcome 3 to 6 months after the last injection.
方法:从2个角度进行数据分析:单次注射,每次注射将所有测量结果分组,基线定义为注射日,以评估单次注射的药代动力学。多次注射,定义为两次或以上注射,两次注射之间间隔3到6个月,分析最后一次注射后3到6个月的结果。
Results:Overall, 762 injections were administered to 340 eyes of 287 patients. Injection series analysis included 171 series in 171 eyes of 150 patients, for a total of 444 injections, with a mean follow-up of 1.7±0.8 years. Of the 762 injections analyzed per injection, 22.7% achieved a 15-letter or more improvement, and 37.8% achieved a 10-letter or more improvement. Mean time to peak improvement was 81.9±39.7 days. Mean maximum change in central macular thickness (CMT) was –174±171 μm. Overall, 7.6% lost 15 or more letters. More eyes with early DME gained 10 or more letters and fewer eyes lost 10 or more letters compared with eyes with late DME (47.4% vs. 33.9% [P = 0.001] and 8.2% vs. 13.5% [P = 0.029], respectively). Patients with controlled diabetes showed greater CMT reduction (P = 0.0002). A higher percentage of treatment-naive patients gained 10 or 15 letter or more in BCVA (P = 0.001 and P = 0.006, respectively). Intraocular pressure elevation of more than 25 mmHg was found following 7.9% of injections; no endophthalmitis was reported.
结果:总体上,对287例患者的340眼进行了762次注射。注射系列分析包括150例患者的171只眼的171个系列,共444次注射,平均随访时间为1.7±0.8年。在762次注射的每次分析中,22.7%的提高了15个字母或以上,37.8%的提高了10个字母或以上。达到提高的峰值的平均时间为81.9±39.7天。黄斑区中心凹厚度(CMT)的平均最大变化为–174±171μm。总体而言,7.6%的患者降低了15个或以上的字母。与晚期DME相比,早期DME中更多的眼睛提高10个或以上的字母,较少的眼睛降低10个或以上字母(分别为47.4%对33.9%[P = 0.001]和8.2%对13.5%[P = 0.029] )。控制的糖尿病患者的CMT减小更明显(P = 0.0002)。未接受治疗的患者中,BCVA获得10或15个字母或更多的比例更高(分别为P = 0.001和P = 0.006)。7.9%的注射后眼内压升高超过25 mmHg;没有眼内炎的报道。
Conclusion:Dexamethasone implant is an effective and safe treatment for DME. Peak improvement was achieved 3 months after injection and dissipated thereafter. Clinicians and providers may consider shortening treatment intervals.
结论:地塞米松植入物对于DME是一种有效而安全的治疗方法。注射后3个月达到改善的峰值,此后消失。临床医生和供应商可以考虑缩短治疗间隔。
推荐理由:此研究深入分析和描述了地塞米松植入物注射系列中每个植入物的实际治疗情况,评估了地塞米松玻璃体内植入物每次注射药效学以及临床和解剖学作用,以及注射系列的疗效和安全性,得出了DME患者的最佳地塞米松治疗频率。
该研究是以真实临床场景为研究环境,不进行过多人为设定,研究对象异质性高,外部有效性好。DNE患者中玻璃体VEGF的含量高,地塞米松玻璃体内植入物治疗与普通的VEGF拮抗剂的治疗机理不同,地塞米松具有强大的抗炎作用,抑制VEGF的分泌,在眼内可以阻断各种炎症介质的释放、降低血管通透性、稳定血-视网膜屏障从而缓解DME,且一次注药可维持3~6个月。而VEGF拮抗剂是中和玻璃体中的VEGF浓度,针对DME处于不同的病理时期可以进行不同的选择。该研究也存在一定的局限性:排除了青光眼或有高眼压病史(未经药物治疗)的患者入选,不能完全代表真实情况;地塞米松对晶状体混浊有一定影响,但没有进行观察;除了视力之外,没有其他的功能性指标,如视野等。

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