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Corneal Epithelial Toxicity after Intravitreal Methotrexate Injection for Vitreoretinal Lymphoma: Clinical and In Vitro Studies

机译:玻璃氨酸甲醇溶解后的角膜上皮毒性培养物尿道淋巴瘤:临床和体外研究

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Methotrexate is widely used as an intraocular chemotherapy for vitreoretinal lymphoma (VRL). Although corneal toxicity has been reported in patients after intravitreal methotrexate injections, the incidence, outcome, and mechanism of the toxicity are unclear. Herein, we performed a clinical study to evaluate the incidence, predisposing factors, and treatment outcome of corneal epitheliopathy associated with intravitreal methotrexate injection. In addition, we directly investigated cytotoxic effects and mechanisms of methotrexate in cultures of human corneal epithelial cells (CECs). Medical chart reviews revealed that corneal epitheliopathy occurred in 15 eyes (22.7%, 12 patients) out of 66 eyes (45 patients) after intravitreal methotrexate injections for treatment of VRL. The use of topical anti-glaucoma medication was significantly associated with development of corneal epitheliopathy. The epitheliopathy resolved in all patients 2.4 months after onset. In culture, methotrexate decreased the survival of CECs by inducing apoptosis, increasing oxidative stress, suppressing proliferation, and upregulating inflammatory cytokines. The addition of folinic acid significantly protected the cells from the methotrexate-induced toxicity. Hence, our results suggest that care should be taken to minimize the contact of methotrexate with corneal epithelium during injection, and folic or folinic acid supplementation might be beneficial for preventing corneal complications in patients undergoing intravitreal methotrexate injections.
机译:甲氨蝶呤被广泛用作培养物淋巴瘤(VRL)的眼内化疗。虽然在玻璃手甲醇甲酸甲醇甲酸甲醇甲酸甲醇甲酸甲醇甲酸甲醇注射后报道了角膜毒性,但毒性的发病率,结果和机制尚不清楚。在此,我们进行了临床研究,以评估与玻璃手甲醛注射液相关的角膜上皮病的发病率,易感因素和治疗结果。此外,我们直接研究了人角膜上皮细胞(CEC)培养物中甲氨蝶呤的细胞毒性效应和机制。医疗图表评论显示,在含有66只眼(45名患者)的含有66只眼(45名患者)中发生的角膜上皮病发生在含有66只眼(45名患者)中,甲醛注射治疗VRL。局部抗青光眼药物的使用与角膜上皮病的发展显着相关。上皮病在所有患者中都解决了2.4个月后发病后。在培养中,甲氨蝶呤通过诱导细胞凋亡,增加氧化应激,抑制增殖和上调炎性细胞因子来降低CEC的存活。添加叶酸的加入显着保护细胞免受甲氨蝶呤诱导的毒性。因此,我们的研究结果表明,应注意在注射期间最小化甲氨蝶呤与角膜上皮的接触,叶片或叶酸补充剂可能有利于预防接受玻璃手甲醛注射患者的角膜并发症。

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