Department of Ophthalmology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Retina. 2012 Jul;32(7):1395-402. doi: 10.1097/IAE.0b013e31823496a3.
The purpose of this study was to demonstrate the effect of intravitreal methotrexate (MTX) in the treatment of refractory retinal vasculitis due to Behcet disease and to evaluate the changes in aqueous humor cytokines after intravitreal MTX.
Seven eyes of seven patients with Behcet disease were assessed. Patients had unilaterally active retinal vasculitis that failed to respond to conventional treatment, together with a history of increased intraocular pressure or intolerance to corticosteroid administration. Intravitreal injection of 400 μg MTX was given monthly until visual acuity and intraocular inflammation were stable. Aqueous humor samples were obtained from the patients before MTX injection and from nine eyes during cataract surgery as a control group. Changes in visual acuity with the Early Treatment Diabetic Retinopathy Study Chart, fluorescein angiographic leakage, and ocular complications associated with intravitreal injection were analyzed. Aqueous humor cytokine levels were measured by proteomic analysis using a multianalyte biochip array system.
Visual acuity improved significantly during a mean follow-up of 24.9 ± 8.2 weeks with a mean improvement from baseline visual acuity of 3.3 ± 2.6 lines after a mean of 4.3 ± 1.0 injections. Six patients (85.7%) showed an increase in visual acuity by 3 or more lines, and 4 patients exhibited a decrease in fluorescein leakage. Change in intraocular pressure after intravitreal MTX was not significant. The aqueous humor levels of interleukin (IL) -6, IL-8, vascular endothelial growth factor, and monocyte chemotactic protein 1 were significantly higher in patients with Behcet disease compared with controls. The levels of IL-6 and IL-8 were significantly reduced at 4 weeks after intravitreal MTX, whereas those of vascular endothelial growth factor and monocyte chemotactic protein 1 were not reduced.
Increased intraocular levels of IL-6, IL-8, vascular endothelial growth factor, and monocyte chemotactic protein 1 may be responsible for refractory retinal vasculitis in Behcet disease. Intravitreal MTX was associated with a significant reduction of IL-6 and IL-8 levels and was effective and well tolerated even in steroid responders with refractory retinal vasculitis due to Behcet disease.
本研究旨在探讨玻璃体内甲氨蝶呤（MTX）治疗贝赫切特病（BD）所致难治性视网膜血管炎的疗效，并评估玻璃体内 MTX 治疗后房水细胞因子的变化。
评估了 7 名 BD 患者的 7 只眼。患者均为单侧活动期视网膜血管炎，经常规治疗无效，且伴有眼压升高史或不能耐受皮质类固醇治疗。每月给予玻璃体内注射 400μg MTX，直至视力和眼内炎症稳定。在 MTX 注射前从患者眼内获得房水样本，并从 9 只眼（作为对照组）在白内障手术期间获得房水样本。分析视力（采用早期治疗糖尿病视网膜病变研究图表）、荧光素血管造影渗漏以及与玻璃体内注射相关的眼部并发症的变化。采用多分析物生物芯片阵列系统的蛋白质组学分析方法测量房水细胞因子水平。
在平均 24.9±8.2 周的随访期间，平均视力从基线视力的 3.3±2.6 线提高到平均 4.3±1.0 次注射后的 3.3±2.6 线，视力显著提高。6 名患者（85.7%）视力提高 3 行或以上，4 名患者荧光素渗漏减少。玻璃体内 MTX 后眼压变化无显著性差异。BD 患者房水中白细胞介素（IL）-6、IL-8、血管内皮生长因子和单核细胞趋化蛋白 1 的水平明显高于对照组。玻璃体内 MTX 治疗 4 周后，IL-6 和 IL-8 水平显著降低，而血管内皮生长因子和单核细胞趋化蛋白 1 水平未降低。
IL-6、IL-8、血管内皮生长因子和单核细胞趋化蛋白 1 可能是导致 BD 难治性视网膜血管炎的原因。玻璃体内 MTX 与 IL-6 和 IL-8 水平的显著降低有关，即使在对 BD 所致难治性视网膜血管炎的类固醇反应者中，也具有良好的效果和耐受性。
