Department of Ophthalmology, Leiden University Medical Centre, Leiden, the Netherlands.
Department of Internal Oncology, Erasmus University Medical Centre-Daniel den Hoed Cancer Centre, Rotterdam, the Netherlands.
Acta Ophthalmol. 2018 Nov;96(7):712-718. doi: 10.1111/aos.13677. Epub 2018 Jan 16.
To analyse ophthalmological adverse events associated with mitogen-activated protein kinase kinase (MEK) inhibition with pimasertib treatment for metastatic cutaneous melanoma (CM).
In this prospective observational, cohort-based, cross-sectional study, eight patients treated with the MEK inhibitor pimasertib received a complete ophthalmic examination. This included Early Treatment of Diabetic Retinopathy Study best-corrected visual acuity, visual field testing, colour vision testing, slit-lamp examination, applanation tonometry, indirect ophthalmoscopy, digital colour fundus photography and optical coherence tomography (OCT). In selected cases, fluorescein angiography was performed.
Serous subretinal fluid (SRF) developed in all patients, within a time frame of 9-27 days after the start of treatment. The fovea was involved in six of eight patients (75%). None of the patients with foveal SRF [excluding a patient who developed a bilateral retinal vein occlusion (RVO)] experienced visual symptoms. Subretinal fluid (SRF) decreased or resolved in all patients, despite continuation of study medication in six of eight patients (75%). Complaints in the CM patient (13%) consisted of experiencing a dark fleck in the inferior part of the visual field of the right eye 1 week after the start of treatment, due to an RVO. Subsequent intravitreal bevacizumab treatment resulted in functional and anatomical improvement.
Patients with metastatic CM who are treated with the MEK inhibitor pimasertib are at high risk of development of ocular adverse events including serous retinopathy and possibly RVO, stressing the need of adequate ophthalmological follow-up including OCT during administration of pimasertib, despite the fact that SRF generally does not lead to ophthalmological complaints.
分析与 MEK 抑制剂 pimasertib 治疗转移性皮肤黑色素瘤(CM)相关的眼不良事件。
在这项前瞻性观察性、基于队列的横断面研究中,8 名接受 MEK 抑制剂 pimasertib 治疗的患者接受了全面的眼科检查。这包括糖尿病视网膜病变早期治疗研究最佳矫正视力、视野测试、色觉测试、裂隙灯检查、眼压计检查、间接检眼镜检查、数字彩色眼底摄影和光学相干断层扫描(OCT)。在选定的情况下,进行荧光素血管造影。
所有患者在治疗开始后 9-27 天内均出现浆液性视网膜下积液(SRF)。8 名患者中有 6 名(75%)累及黄斑。没有一名患有黄斑 SRF 的患者(不包括一名发生双侧视网膜静脉阻塞(RVO)的患者)出现视觉症状。尽管 8 名患者中有 6 名(75%)继续使用研究药物,但所有患者的视网膜下液(SRF)均减少或消退。CM 患者(13%)的抱怨包括在治疗开始后 1 周因 RVO 而出现右眼下方视野出现暗斑。随后进行玻璃体内贝伐单抗治疗导致功能和解剖学改善。
接受 MEK 抑制剂 pimasertib 治疗的转移性 CM 患者发生眼部不良事件(包括浆液性视网膜病变和可能的 RVO)的风险较高,这强调了在给予 pimasertib 期间需要进行充分的眼科随访,包括 OCT,尽管 SRF 通常不会导致眼部不适。