Subretinal Fluid Associated With MEK Inhibitor Use in the Treatment of Systemic Cancer
Subretinal Fluid Associated With MEK Inhibitor Use in the Treatment of Systemic Cancer
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DOI：
10.1001/jamaophthalmol.2016.0090
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发表时间：
2016-08-01
影响因子：
8.1
通讯作者：
Heier, Jeffrey S.
中科院分区：
文献类型：
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作者：
Weber, Marissa L.;Liang, Michelle C.;Heier, Jeffrey S.
丝裂原活化蛋白激酶（MAPK）激酶（MEK）抑制剂的使用在全身性癌症的治疗中变得越来越普遍。这些药物与一些患者的中心浆液性视网膜病变有关。识别这些视网膜发现和这些事件的相对良性性质对于避免不必要的干预是重要的，包括停止潜在的延长生命的药物治疗。目的评价与在治疗系统性癌症中使用MEK抑制剂相关的视网膜下液（SRF）的存在和特征，并将SRF的存在与随时间的视敏度和症状相关联。和参与者对前瞻性收集的数据进行事后分析，这些数据来自4项临床试验中的1项，其中51例患有局部晚期或转移性癌症并接受MEK抑制剂比尼替尼治疗的患者。所有临床试验参与者在马萨诸塞州波士顿的一家私人诊所接受了视网膜专家的全面眼科检查，并在2012年2月29日至2014年1月8日期间接受了监测。检查包括基线时Snellen测量的视力、散瞳眼底检查和光谱域光学相干断层扫描，每两周一次，持续2个月，然后在剩余的试验参与期间每月一次。2013年12月1日至2014年6月20日期间进行了事后设计和数据分析。主要结果和指标视觉症状、视力、眼底外观以及光学相干断层扫描仪上记录的SRF的存在和特征。血管造影片的特点进行了审查，在治疗医生的自由裁量权。结果的51名参与者中，18（35%）是男性，平均（SD）年龄为60（13）岁（范围，32-87岁）。46名（90%）研究参与者在研究期间发生了SRF，其中9名（20%）在任何时候都出现了症状。39名首次就诊时发生SRF的研究参与者的平均（SD）中央视网膜厚度从基线时的280（26）μ m增加到开始binimetinib治疗后首次就诊时的316（43）μ m（配对t检验，P < .001）。在检查中，SRF表现为中央凹和/或沿着沿着的升高的黄橙色囊袋。相应的光学相干断层成像显示SRF下的交错区。46人中有37人（80%）的中央凹受到影响; SRF积累的位置各不相同。视觉症状轻微，主要是短暂的，发生在9名参与者与SRF（20%; 95% CI，10%-33%）。仅2例受试者（4%）在终止binimetinib治疗后的末次研究访视时发现SRF。两人的Snellen测量视力为20/25或更好。结论和相关性SRF的存在是常见的研究参与者接受治疗的MEK抑制剂binimetinib。视觉症状轻微，主要是短暂的。SRF的存在不会导致永久性眼部后遗症。当存在SRF时，不需要停止MEK抑制剂延长寿命的治疗。
IMPORTANCE The use of mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitors has become more common in the treatment of systemic cancer. These agents have been associated with a central serous-like retinopathy in some patients. Recognition of such retinal findings and the relatively benign nature of these events is important to avoid unnecessary intervention, including the cessation of a potentially life-prolonging medication.OBJECTIVES To evaluate the presence and characteristics of subretinal fluid (SRF) associated with the use of MEK inhibitors in the treatment of systemic cancer and to correlate the presence of SRF with visual acuity and symptoms over time.DESIGN, SETTING, AND PARTICIPANTS Post hoc analysis was conducted of prospectively collected data from 51 patients with locally advanced or metastatic cancer undergoing treatment with the MEK inhibitor binimetinib in 1 of 4 clinical trials. All clinical trial participants underwent complete ophthalmic examination by retina specialists at a private practice in Boston, Massachusetts, and were monitored between February 29, 2012, and January 8, 2014. The examination included Snellen-measured visual acuity, dilated fundus examination, and spectral-domain optical coherence tomography at baseline, biweekly for 2 months, then monthly for the remainder of their trial participation. Post hoc design and data analysis were performed between December 1, 2013, and June 20, 2014.MAIN OUTCOMES AND MEASURES Visual symptoms, visual acuity, fundus appearance, and the presence and characteristics of SRF noted on optical coherence tomography. The characteristics of angiograms performed at the discretion of the treating physician were reviewed.RESULTS Of the 51 participants, 18 (35%) were men; the mean (SD) age was 60 (13) years (range, 32-87 years). Forty-six (90%) study participants developed SRF during the study period, with 9 (20%) experiencing symptoms at any point. The mean (SD) central retinal thickness of 39 study participants who developed SRF at the first visit increased from 280 (26) mu m at baseline to 316 (43) mu m at the first visit after starting binimetinib treatment (paired t test, P < .001). On examination, SRF appeared as elevated, yellow-orange pockets in the fovea and/or along the arcades. Corresponding optical coherence tomographic imaging revealed SRF beneath the interdigitation zone. The fovea was affected in 37 of 46 (80%) individuals; the location of SRF accumulation varied. Visual symptoms were mild and mainly transient, occurring in 9 participants with SRF (20%; 95% CI, 10%-33%). Only 2 participants (4%) were found to have SRF at the last study visit after discontinuation of treatment with binimetinib. Both had Snellen-measured visual acuity of 20/25 or better.CONCLUSIONS AND RELEVANCE The presence of SRF was common in study participants undergoing treatment with the MEK inhibitor binimetinib. Visual symptoms were mild and mainly transient. The presence of SRF did not lead to permanent ocular sequelae. Cessation of life-extending treatment with MEK inhibitors is not indicated when SRF is present.