Retina and Inflammation division, MIOS sa , Avenue du Léman 32, Lausanne 1005 , Switzerland
Expert Opin Biol Ther. 2013 Dec;13(12):1741-7. doi: 10.1517/14712598.2013.853737.
Diabetic retinopathy is a serious public health concern. Vision impairment follows from intraocular vascular proliferation known as proliferative diabetic retinopathy (PDR) and/or from diabetic macular edema (DME). Clinical acumen and a recent meta-analysis of published studies suggest that the presence of a posterior vitreous detachment (PVD) reduces the risk of developing PDR, and has a favourable impact on DME. Pharmacologic vitreolysis by ocriplasmin or other agents may provide a minimally invasive method of achieving a PVD. If demonstrated in appropriate clinical studies including randomized trials, it would provide an interesting approach to prevent advanced and blinding stages of diabetic retinopathy, particularly in areas where access to care is limited.
The current epidemiology of diabetic retinopathy is reviewed as well as the role of the vitreous and its separation from the retina known as a PVD in DR based on a recent meta-analysis of published literature regarding the contribution of complete, partial or absent PVD to PDR and DME. The principles underlying vitreolysis and the induction of PVD are reviewed as well as the challenges faced by a pharmacologic approach. The results of clinical trials on the use of ocriplasmin are analyzed regarding its possible use in DR.
Ocriplasmin has the ability to liquefy the vitreous and induce a PVD in a statistically significant number of patients. However, current studies on patients with vitreomacular adhesion and traction suggest that the majority of patients would not achieve a PVD with a single injection. As shown in the meta-analysis, a complete PVD is required to significantly reduce the risk of PDR, while a partial PVD may worsen the prognosis. If a strategy can be developed that insures a complete PVD within an appropriate time interval, the prevention of PDR might become a realistic target for ocriplasmin or other vitreolytic agents. In DME, release of traction whether complete or partial is associated with a reduction in DME, which in several cases has resulted in improved vision. While no studies have been conducted on the use of ocriplasmin or other vitreolytic agents in DR, a few studies using plasmin indicate that it is likely to have a beneficial effect in DME. Based on the information available, randomized clinical trials would be required to evaluate the clinical relevance of ocriplasmin and other potential vitreolytic agents in both forms of DR. Such trials could determine the efficacy of this strategy as compared to prophylatic laser particularly in high-risk populations. New follow-up and treatment strategies would also be required should initial studies be encouraging.
糖尿病性视网膜病变是一个严重的公共卫生问题。眼内血管增殖导致的视力损害称为增生性糖尿病性视网膜病变(PDR)和/或糖尿病性黄斑水肿(DME)。临床敏锐度和最近对已发表研究的荟萃分析表明,后玻璃体脱离(PVD)的存在降低了发生 PDR 的风险,并对 DME 有有利影响。玻璃体内溶解酶(如 ocriplasmin 或其他药物)可能提供一种微创方法来实现 PVD。如果在适当的临床研究中得到证实,包括随机试验,它将为预防糖尿病性视网膜病变的晚期和致盲阶段提供一种有趣的方法,特别是在获得治疗机会有限的地区。
本文综述了糖尿病性视网膜病变的当前流行病学,以及玻璃体及其与视网膜分离(称为 PVD)在 DR 中的作用,这是基于最近对有关完全性、部分性或无 PVD 对 PDR 和 DME 贡献的文献的荟萃分析。本文还回顾了玻璃体内溶解的原理以及诱导 PVD 的原理,以及药物治疗方法所面临的挑战。分析了 ocriplasmin 治疗临床试验的结果,探讨了其在 DR 中的可能应用。
Ocriplasmin 具有使玻璃体液化并在统计学上显著数量的患者中诱导 PVD 的能力。然而,目前关于玻璃体黄斑粘连和牵引的研究表明,大多数患者单次注射不会形成 PVD。正如荟萃分析所示,完全性 PVD 是显著降低 PDR 风险所必需的,而部分性 PVD 可能会使预后恶化。如果能够开发出一种策略,确保在适当的时间间隔内形成完全性 PVD,那么预防 PDR 可能成为 ocriplasmin 或其他玻璃体内溶解酶的现实目标。在 DME 中,无论是完全性还是部分性的牵引释放都与 DME 的减少有关,这在几种情况下导致了视力的改善。虽然尚未在 DR 中进行 ocriplasmin 或其他玻璃体内溶解酶的使用研究,但一些使用纤溶酶的研究表明,它在 DME 中可能有有益的效果。基于现有信息,需要进行随机临床试验来评估 ocriplasmin 和其他潜在玻璃体内溶解酶在两种形式的 DR 中的临床相关性。与预防性激光治疗相比,此类试验可能会确定该策略的疗效,特别是在高危人群中。如果初始研究令人鼓舞,还需要新的随访和治疗策略。