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精“英”视界丨干性AMD的治疗新进展

玻璃体视网膜  作者:国际眼科时讯  2021/12/7 16:39:00
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内容概要:AMD是老年人群中常见的眼病,分为干性和湿性两种,治疗的方法也各不相同。

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编者按:AMD是老年人群中常见的眼病,分为干性和湿性两种,治疗的方法也各不相同。上一期,Wills 眼科医院视网膜科的Ajay Kuriyan医生主要讲述了湿性AMD的相关研究治疗进展。然而干性AMD的治疗才更加棘手,尚无临床广泛证明有效的治疗方法,但相关临床研究一直在进行中。针对干性AMD的治疗目前有哪些突破?本期Ajay Kuriyan医生将继续给出他的看法。

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Syed医生:有道理。我认为我们已经对湿性AMD的治疗进行了深入的探讨,所以让我们谈谈干性AMD。对于这种情况的患者会出现什么疗法。
 
Dr Syed: That makes sense. I think we have chatted enough about wet AMD, so let’s move on to dry AMD. What therapies are coming up for patients with this condition?
 
Kuriyan医生:对于干性AMD患者来说,这也是一个非常令人兴奋的时刻。长期以来,我们一直在告诉干性AMD患者我们没有任何可用的治疗方法。现在,我们进行了大量的临床试验,这些试验基本上是针对地图状萎缩进行的,这是干性AMD研究的重点。有一些研究基于具有良好视力的患者,旨在延缓疾病的进展,这主要集中在补体抑制研究上。还有其他研究针对视力非常差的患者,并旨在恢复视力。补体抑制主要是通过玻璃体内注射,II期临床研究证实其在减缓疾病进展方面有一定作用。视力恢复的工作更多地集中在尝试替换或补充因地图状萎缩而丢失的某些细胞。这主要集中在视力不佳的患者上,以查看这些治疗是否可行。比如干细胞疗法旨在重建一些丢失的RPE细胞和感光细胞。同时,基因治疗方面正在进行一些努力,试图将非感光细胞转变为感光细胞,从而在因地图状萎缩丧失外层视网膜的眼睛中产生了一些视觉。最后是一些光电设备,它们的功能与我们熟悉的治疗色素性视网膜炎的Argus植入物非常相似,在这种情况下,我们使用视频信号来刺激植入的电极阵列或光电二极管阵列来刺激仍完整的内部视网膜。
 
Dr Kuriyan: This is also a very exciting time for dry AMD. For a long time we have been telling patients with dry AMD that we didn’t have any treatments available. Now, we have a bunch of clinical trials that are going on essentially for geographic atrophy. That is the main focus for these dry AMD studies. There are studies based on patients who have fairly good vision and aiming to slow down disease progression. This is mainly focused on complement inhibition. Then there are other studies focused on patients with very bad vision and aimed at vision restoration. The complement inhibition is mostly by intravitreal injections, and we are monitoring those studies to see how those results pan out, but the phase II studies are fairly promising in slowing down progression. The vision restoration efforts are more focused at trying to replace or replenish some of the cells lost in geographic atrophy. This is focused mainly on the very poor-seeing patients at this point to see if these treatments are feasible. There are stem cell therapies aimed at recreating some of the lost RPE cells and photoreceptors. There are some efforts towards gene therapy looking at potential treatment modalities that turn non-light-sensing cells into light-sensing cells to create some vision in an eye that has lost a lot of the outer retina to geographic atrophy. Lastly, there are optoelectrical devices that function very similarly to the Argus implant that we are familiar with for retinitis pigmentosa, where we use a video feed to stimulate an implanted electrode array or photodiode array to stimulate the inner retina that is still intact.
 
Syed医生:因此,这些是非常有前途的疗法。对于您刚才提到的三个方面,是否有您特别感兴趣的地方?
 
Dr Syed: So these are a lot of very promising therapies. Are there any that you have a particular interest in or that you feel particularly excited about of the three you just mentioned?
 
Kuriyan医生:视力恢复的疗法还在摸索过程中。对于基因治疗方法和干细胞治疗方法,我们主要关注安全性,然后着眼于原理证明。我们可以将细胞放入其中,并使它们持久作用,以便可以将这些细胞转变为感光细胞。在光电装置方面,由于我们在治疗色素性视网膜炎的使用历史较长,因此我认为就速度而言,光电装置可能会更早得到应用。话虽如此,我们对其他两个选择仍然感到非常兴奋。 
 
Dr Kuriyan: The vision restoration is still in the process of seeing where it can lead. For the gene therapy approaches and stem cell therapy approaches we are mostly looking at safety, and then focusing on the proof of principle – that we can put cells in there and that they last and work, so we can change these cells into light-sensing cells and that they respond. In terms of the optoelectrical devices, we have a longer history with that in retinitis pigmentosa, so I think in terms of being available quicker, that will probably be available sooner for patients with a more proven track record. That being said, we are still very excited about the other two options as well.
 
Syed医生:我很好奇听到更多关于补体抑制注射的信息,它与向玻璃体内注射糖皮质激素等常规抗炎药有何不同?
 
Dr Syed: I am curious to hear more about complement inhibition injections? How is that different from injecting a regular anti-inflammatory like a steroid into the vitreous?
 
Kuriyan医生:这是一个很好的问题。我们知道补体在AMD中是非常重要的角色,而炎症在AMD中也是非常重要的角色。人们已经为AMD使用了广泛的抗炎注射剂,例如糖皮质激素,但结果令人喜忧参半,目前我们无法继续进行。可能有一部分患者确实从某些抗炎治疗中受益,至少在II期研究中,我们发现补体抑制确实会减慢地图状萎缩的进展。我认为这是向患者强调的重要内容,这些治疗方法并非旨在恢复已经失去的视力,而是旨在防止视力进一步下降。
 
Dr Kuriyan: That’s a great question. One of the first genetic links for diseases in all medicine was for AMD and finding the complement factor relationship. We know that complement is a very important player in AMD, and that inflammation is a very important player in AMD. People have looked at broad anti-inflammatory injections, like steroids, for AMD, and those results have been very mixed and not something we can move forward with at this point. There may be a subset of patients who do benefit from some anti-inflammatory treatments, but we are finding, at least in the phase II studies, that complement inhibition does slow the progression of geographic atrophy. I think that is something important to stress to patients. At this point, those treatments are not designed to restore the vision that has already been lost; it is more designed to prevent further vision loss.
 
Syed医生:关于干细胞疗法,我们正在使用哪些干细胞,它们是从哪里获得的?
 
Dr Syed: Regarding the stem cell therapy, whose stem cells are we using and where are they obtained from?
 
Kuriyan医生:有几种不同的方法。有一些储存的胚胎干细胞可用于此类应用,而这些都不是患者自己的干细胞。干细胞疗法确实已经发展到可以从体内取出任何细胞,将其转变为干细胞,然后利用它来创建您所选择的任何细胞的地步。来自皮肤或其他部位的多能干细胞可以产生RPE细胞,该RPE细胞在技术和基因上与患者的RPE细胞完全相同。它们可用于替换丢失的RPE细胞,甚至可以以片状形式提供,以代替地图状萎缩中丢失RPE的整个区域。 
 
Dr Kuriyan: There are a few different approaches for that. There are some stored embryonic stem cells that can be used for these kinds of applications, and those would not be your own stem cells. Stem cell therapy has really advanced to the point that you can take any cell from your body, turn that into a stem cell, and then use it to create the cell of your choice. That is another approach that is being done, where infused pluripotent stem cells from your skin or somewhere else, can be turned into RPE cells that are technically and genetically identical to your RPE cells. They can be used to replace the lost cells. That can even be delivered as a sheet to replace the entire area of lost RPE in geographic atrophy.
 
Syed医生:如何实现呢?那实际上是手术,你能具体告诉我们吗?
 
Dr Syed: How would you deliver that? That would actually be a surgery. Can you tell us about that?
 
Kuriyan医生:有几种不同的方法。当只是在做胚胎干细胞时,它们可以作为视网膜下气泡注入。操作者可以取一个非常细的套管,刺穿视网膜,并在需要干细胞的地方形成一个气泡。对于片状RPE,它需要更细致的技术。操作者需要在视网膜内开一个更大的开口,然后将RPE薄片滑入视网膜下进入黄斑。 
 
Dr Kuriyan: There are a few different approaches. When you are just doing embryonic stem cells, they can be injected as a subretinal bleb. We can take a very fine cannula, pierce the retina, and create a bleb where the stem cells need to be. For the RPE sheets, it’s a little more entailed. You need to make a larger opening within the retina itself, and slip the RPE sheet under the retina into the macula.
 
Syed医生:因此,在视网膜领域发生了一些很酷的进步。一切都非常令人兴奋。在我们的最后几分钟,对于那些多次注射的患者,可能会有很多痛苦,有什么方法可以改善这些患者的疼痛体验?  
 
Dr Syed: So there are some cool advances happening in the field of retina. It’s all very exciting. In our last couple of minutes, for those patients who get a lot of injections, there can be a lot of pain. Is there anything in the pipeline to improve pain control for these patients?
 
Kuriyan医生:这也是一个令人兴奋的领域。在过去很长的时间里,我们基本上依靠局部滴剂或凝胶剂表面麻醉或结膜下注射利多卡因。现在,我们正在研究两种不同的设备来冷却眼睛,从而在非常集中的区域对眼睛进行冷却,使神经在注射时不会感到疼痛。这样做的好处是,它消除了出血的可能,而且它往往很快起效。因此,我们对这些技术感到非常兴奋。它们处于开发的早期阶段,但是初步研究看起来非常有前途。
 
Dr Kuriyan: That is also an exciting area. For the longest time, we have basically relied on topical drops or gel, or subconjunctival lidocaine. That has been the main focus for pain control. Now we have two different devices that are being studied to cool the eye, resulting in a very focused area where the eye is cooled causing nerves to not feel pain while getting the injection. The great thing about it is it eliminates the potential for hemorrhage and things like that associated with our current pain management techniques. And it tends to be very quick. So we are very excited about these technologies. They are in the early stages of development, but the initial studies have looked very promising.
 
Syed医生:到底是什么?是冷冻探针还是其他类似的东西?  
 
Dr Syed: What is it exactly? Is it a cryoprobe or something similar?
 
Kuriyan医生:这不是冷冻探针,而是用于注射的特定设备。有两种不同的设备,两种设备的接触的表面积都非常小,就在注射部位的结膜上。它可以在不会给患者带来痛苦的温度下提供快速冷却。
 
Dr Kuriyan: It is not a cryoprobe. It is a specific device for these injections. There are two different devices, both of which have very small surface areas that go right on the conjunctiva at the injection site. It provides rapid cooling at a temperature that shouldn’t cause pain for the patient.
 
Syed医生:就只是在您要注射的那个位置,我想一个冷冻探头可能太大了。
 
Dr Syed: And just in that one spot where you would be injecting. I guess a cryoprobe would be too large for that.
 
Kuriyan医生:它会比较大,而且不需要特殊控制就能提供所需的准确温度达到良好的麻醉效果,而又不导致细胞死亡。
 
Dr Kuriyan: It would be large and a little less controlled in terms of being able to deliver the exact temperature you want without any cell death, but with the anesthesia that you want.
 
Syed医生:Kuriyan医生,这次谈话真是太好了。您还希望听众了解黄斑变性治疗中的其他方式吗? 
 
Dr Syed: This has been a great conversation, Dr Kuriyan. Is there anything else you want our audience to know about what is in the pipeline for macular degeneration therapy?
 
Kuriyan医生:我认为这是一个非常令人兴奋的时期,我们有很多其他治疗AMD的选项正在研究中。我们目前拥有的大多数数据仍来源于II期或更早期的试验,因此我们确实需要进行III期研究,以及在实际采用这些方法后进行随访,以了解这些不同治疗方法的作用。
 
Dr Kuriyan: I think it is just a very exciting time. We have a lot of options that are being studied. Most of the data that we have right now is still in the phase II or early stage data, so we really need these phase III studies, as well as looking to the follow up after these are actually adopted to see how these different treatments are doing. But it is a very exciting time for retina right now.
 
Syed医生:听起来非常令人兴奋。我学到了很多东西。非常感谢您今天早上与我们的分享,感谢大家收看。
 
This sounds super exciting. I’ve learned a ton. Thank you so much for joining me this morning, and thank you all for tuning in.
 
Kuriyan医生:谢谢您,也谢谢大家收看。
 
Dr Kuriyan: Thank you for having me, and thank you all for tuning in.
 
相关单词学习
Word Study
dry AMD 干性AMD 
geographic atrophy 地图状萎缩 
light-sensing cells 感光细胞 
electrode array 电极阵列
vision restoration 视力恢复 
stem cell therapy 干细胞治疗 
complement factor 补体因子
prevent further vision loss  防止视力进一步下降
embryonic stem cells  胚胎干细胞
early stages 早期阶段
Cryoprobe  冷冻探针
 
获取英文音频,后台回复关键词“干性AMD治疗”。
 

 
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