Introduction Many cancers have derangement of the Mitogen-Activated Pathway Kinase (MAPK) making this pathway blockade a therapeutic target. However, inhibitors of MAPK can result in adverse effects including retinopathy. This study compares clinical and morphologic characteristics of serous retinal disturbances in patients taking agents with variable inhibition of MAPK: either direct interference of mitogen-activated protein kinase kinase (MEK) or extracellular signal-regulated kinase (ERK) inhibitors or with indirect inhibition via interference with FGFR signaling. Methods This retrospective observational study of prospectively collected pooled data is from a single tertiary oncology referral center. Of 339 patients receiving MAPK inhibitors (171, 107, 61 on FGFR, MEK and ERK inhibitors, respectively) for treatment of metastatic cancer, this study included 128 eyes of 65 patients with evidence of retinopathy confirmed by optical coherence tomography (OCT). The main outcome was characteristics of treatment-emergent choroid/retinal OCT abnormalities as compared to baseline OCT Results In all patients on one of three drug classes (FGFRi, MEKi, ERKi) the retinopathy manifested as subretinal fluid foci that were bilateral, fovea-involving and reversible without intervention. There were notable differences between the three classes of drugs: the proportion of patients with retinopathy, number of fluid foci per eye, proportion of eyes with intraretinal edema and the proportion of symptomatic patients was least for the upstream target (FGFR inhibitors) and greatest for the downstream targets (MEK or ERK inhibitors). Discussion/conclusion This study shows MAPK pathway inhibitors may cause subretinal fluid foci with unique clinical and morphologic characteristics depending on the target (FGFR, MEK or ERK) implicated. Retinopathy is more common, more symptomatic and more severe (more fluid foci, more expansive fluid configurations) the further downstream the MAPK pathway is inhibited.


中文翻译：

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有丝分裂原激活通路激酶 (MAPK) 抑制剂相关性视网膜病变：上游抑制与下游抑制的特征是否不同？

前言 许多癌症的丝裂原激活通路激酶 (MAPK) 发生紊乱，使得该通路阻断成为治疗靶点。然而，MAPK 抑制剂可导致不良反应，包括视网膜病变。本研究比较了服用 MAPK 可变抑制药物的患者浆液性视网膜障碍的临床和形态学特征：有丝分裂原活化蛋白激酶激酶 (MEK) 或细胞外信号调节激酶 (ERK) 抑制剂的直接干扰或通过干扰的间接抑制与 FGFR 信号。方法 这项前瞻性收集的汇总数据的回顾性观察研究来自一个三级肿瘤转诊中心。在接受 MAPK 抑制剂治疗的 339 名患者中（分别有 171 名、107 名、61 名接受 FGFR、MEK 和 ERK 抑制剂）治疗转移性癌症，这项研究包括 65 名患者的 128 只眼睛，这些患者有经光学相干断层扫描 (OCT) 证实的视网膜病变证据。主要结果是与基线 OCT 结果相比，治疗中出现的脉络膜/视网膜 OCT 异常的特征 在所有接受三种药物类别（FGFRi、MEKi、ERKi）之一的患者中，视网膜病变表现为双侧视网膜下液灶，累及中央凹并且无需干预即可逆转。三类药物之间存在显着差异：视网膜病变患者比例、每只眼液灶数量、视网膜内水肿眼比例和有症状患者比例对于上游靶点（FGFR 抑制剂）最小，对于最大下游目标（MEK 或 ERK 抑制剂）。讨论/结论 本研究表明，MAPK 通路抑制剂可能会导致具有独特临床和形态学特征的视网膜下液灶，具体取决于所涉及的靶点（FGFR、MEK 或 ERK）。MAPK 通路的下游受抑制越远，视网膜病变越常见、症状越严重且越严重（更多的液体灶、更膨胀的液体配置）。