Corticosteroids in posterior segment disease: an update on new delivery systems and new indications.
Corticosteroids in posterior segment disease: an update on new delivery systems and new indications.
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DOI：
10.1097/01.icu.0000120711.35941.76
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发表时间：
2004-06-01
影响因子：
3.7
通讯作者：
Criswell, Mark H
中科院分区：
文献类型：
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作者：
Ciulla, Thomas A;Walker, Jonathan D;Criswell, Mark H
审查目的：皮质类固醇传统上用于炎性疾病，因为它们能够减少中性粒细胞的迁移，限制进入炎症部位，并减少细胞因子的产生。然而，最近，研究人员已经将注意力集中在皮质类固醇用于后节疾病（诸如年龄相关性黄斑变性（AMD）、糖尿病视网膜病变和黄斑水肿）的血管抑制和抗渗透性质上。新的血管抑制剂和传统的皮质类固醇目前正在进行评估，因为新的递送技术，如玻璃体内注射和眼内缓释装置，促进高的局部血管抑制剂和抗渗透剂浓度，同时最大限度地减少眼外毒性。本次审查的目的是讨论最近的工作有关的机制和有效性，这些较新的treatment.Recent发现：类固醇激素可能会发挥有益的影响AMD相关的脉络膜新生血管膜（CNVM）通过抑制CNVM促进巨噬细胞和直接抑制血管生成生长因子。它们还可能改变细胞外基质代谢并抑制参与CNVM形成的基质金属蛋白酶。玻璃体内类固醇注射有效地抑制灵长类动物和大鼠的实验CNVM，并在一些早期的人类试点试验中显示出希望。在增殖性糖尿病视网膜病变中，类固醇可直接抑制生长因子如血管内皮衍生生长因子，并抑制在早期微血管改变中起重要作用的白细胞。玻璃体内类固醇注射抑制猪和大鼠的实验性视网膜前新生血管形成，以及一些早期人类研究中的发红。此外，类固醇对血管渗透性的作用导致其用于由许多原因如糖尿病和静脉闭塞性疾病引起的黄斑水肿。这些方法的长期安全性和有效性尚未确定，这一事实必须平衡明显的短期成功。目前正在进行一些关于类固醇化合物和新型给药系统治疗AMD、糖尿病视网膜病变、葡萄膜炎和其他视网膜血管疾病的大型随机前瞻性临床试验，希望这些研究将为这些新方法的使用提供指导。
PURPOSE OF REVIEW: Corticosteroids are traditionally used for inflammatory disorders because of their ability to diminish neutrophil transmigration, limit access to sites of inflammation, and decrease cytokine production. More recently, however, investigators have focused on the angiostatic and antipermeability properties of corticosteroids for posterior segment diseases such as age-related macular degeneration (AMD), diabetic retinopathy, and macular edema. Both new angiostatic and traditional corticosteroids are currently undergoing evaluation as new delivery techniques such as intravitreal injection and intraocular sustained-release devices facilitate high local angiostatic and antipermeability concentrations while minimizing extraocular toxicity. The purpose of this review is to discuss recent work concerning both the mechanism and effectiveness of these newer treatments.RECENT FINDINGS: Steroids may exert a beneficial effect in AMD-related choroidal neovascular membranes (CNVM) through inhibition of CNVM-promoting macrophages and direct inhibition of angiogenic growth factors. They may also alter extracellular matrix turnover and inhibit matrix metalloproteinases involved in CNVM formation. Intravitreal steroid injections potently inhibit experimental CNVM in primates and rats and have shown promise in some early human pilot trials. In proliferative diabetic retinopathy, steroids may directly inhibit growth factors such as vascular endothelial derived growth factor and inhibit leukocytes that play an important role in early microvascular alterations. Intravitreal steroid injections inhibit experimental preretinal neovascularization in pigs and rats, and rubeosis in some early human studies. In addition, the effect of steroids on vascular permeability has led to their use for macular edema from many causes such as diabetes and venous occlusive disease.SUMMARY: The use of steroids to treat a number of retinal diseases is gaining wide spread acceptance. The apparent short-term success must be balanced by the fact that the long-term safety and efficacy have yet to be determined for any of these approaches. A number of large randomized prospective clinical trials of steroid compounds and new delivery systems are currently under way for AMD, diabetic retinopathy, uveitis, and other retinovascular diseases, and hopefully these studies will provide guidance about the use of these new modalities.