背景:良好的视力在很大程度上取决于角膜的透明度,这是眼睛的“挡风玻璃”。事实上,由于透明度损失导致的角膜失明是全球第二大最常见的失明原因,而角膜移植是主要的医治办法。重要的是,角膜通常是无血管的,但由于严重的炎症,其次会受到病理(血液和淋巴管)血管的侵袭,角膜移植物的生存预后主要取决于受者角膜的术前血管状况。而移植到无血管的受体床上享有>90%的长期生存率,病理前血管化生存率显着降低,所谓的高风险接受者,在德国,约占所有移植的10%,在全球低收入和中等收入国家>75%。
方法:这种平行分组,开放随机,多中心,前瞻性对照探索性研究人员发起的试验(IIT)旨在通过在高风险角膜移植之前通过(淋巴)血管扩张治疗对病理血管化的受体角膜进行预处理来改善移植物存活率。为此,将使用角膜交联(CXL),已被证明可以有效地消退角膜血液和淋巴管。移植前,患者将随机分为2组:(1)CXL(干预)或(2)无预处理(对照)。如果应观察到角膜新生血管的减少不足,则将重复CXL一次。然后所有患者(两组)都将进行角膜移植。在干预组中,剩余的血管将使用细针透热疗法(在移植当天)进行进一步恢复。之后,移植物排斥反应的发生率将评估24个月(主要终点).移植物总体存活率,以及角膜血管消退和/或复发,在其他因素中,将被分析(次要终点)。
结论:基于临床前和早期试点临床证据,我们希望测试CXL对高危眼进行临时(淋巴)血管造影预处理的新概念,以促进随后的角膜移植物存活.到目前为止,在临床常规的高危角膜移植设置中,没有基于证据的方法可靠地提高移植物的存活率.如果成功,这种方法将是第一个在高风险移植中促进移植物存活的方法。它将显著改善患有角膜盲的患者的视力和生活质量。
背景:ClinicalTrials.govNCT05870566。2023年5月22日注册。
BACKGROUND: Good vision highly depends on the transparency of the cornea, which is the \"windscreen\" of the eye. In fact, corneal blindness due to transparency loss is the second most common cause of blindness worldwide, and corneal transplantation is the main cure. Importantly, the cornea is normally avascular but can secondarily be invaded by pathological (blood and lymphatic) vessels due to severe inflammation, and the survival prognosis of a corneal graft mainly depends on the preoperative vascular condition of the recipient\'s cornea. Whereas transplants placed into avascular recipient beds enjoy long-term survival rates of > 90%, survival rates significantly decrease in pathologically pre-vascularized, so-called high-risk recipients, which account for around 10% of all performed transplants in Germany and > 75% in lower and middle-income countries worldwide.
METHODS: This parallel-grouped, open-randomized, multicenter, prospective controlled exploratory investigator-initiated
trial (IIT) intends to improve graft survival by preconditioning pathologically vascularized recipient corneas by (lymph)angioregressive treatment before high-risk corneal transplantation. For this purpose, corneal crosslinking (CXL) will be used, which has been shown to potently regress corneal blood and lymphatic vessels. Prior to transplantation, patients will be randomized into 2 groups: (1) CXL (intervention) or (2) no pretreatment (control). CXL will be repeated once if insufficient reduction of corneal
neovascularization should be observed. All patients (both groups) will then undergo corneal transplantation. In the intervention group, remaining blood vessels will be additionally regressed using fine needle diathermy (on the day of transplantation). Afterwards, the incidence of graft rejection episodes will be evaluated for 24 months (primary endpoint). Overall graft survival, as well as regression of corneal vessels and/or recurrence, among other factors, will be analyzed (secondary endpoints).
CONCLUSIONS: Based on preclinical and early pilot clinical evidence, we want to test the novel concept of temporary (lymph)angioregressive pretreatment of high-risk eyes by CXL to promote subsequent corneal graft survival. So far, there is no evidence-based approach to reliably improve graft survival in the high-risk corneal transplantation setting available in clinical routine. If successful, this approach will be the first to promote graft survival in high-risk transplants. It will significantly improve vision and quality of life in patients suffering from corneal blindness.
BACKGROUND: ClinicalTrials.gov NCT05870566. Registered on 22 May 2023.