Kunkler Anne L, Binkley Elaine M, Mantopoulos Dimosthenis, Hendershot Andrew J, Ohr Matthew P, Kendra Kari L, Davidorf Frederick H, Cebulla Colleen M
Department of Ophthalmology and Visual Science, Havener Eye Institute, The Ohio State University, Wexner Medical Center, 915 Olentangy River Rd, Ste 5000, Columbus, OH, 43212, USA.
Department of Internal Medicine, Division of Medical Oncology, The Ohio State University, Wexner Medical Center, Columbus, OH, USA.
Graefes Arch Clin Exp Ophthalmol. 2019 Aug;257(8):1771-1781. doi: 10.1007/s00417-019-04337-8. Epub 2019 May 16.
Increases in cancer with an aging population and the rapid development of new chemotherapeutics underscore the need for ophthalmologists to identify and manage potential ocular toxicities. This retrospective case series reports the ocular side effects of traditional and novel chemotherapeutic agents from a large center.
The medical records of 3537 adult patients 18 years and older who presented to an academic ophthalmology department on high-risk medications identified by ICD-9 search between January 2010 and February 2015 were reviewed. A cancer diagnosis, as well as a temporal association with chemotherapeutic use and ocular side effect, was deemed necessary for inclusion in the study. The main measures were ocular side effects in cancer patients taking chemotherapy, ocular imaging abnormalities, and the outcome of each side effect.
Of the 161 oncology patients referred to the ophthalmology clinic for chemotherapeutic screening or ocular side effect, 31 (19.3%) were identified as having an ocular adverse reaction due to a novel or traditional chemotherapeutic medication. A novel flattening of the corneal curvature with hyperopic shift and corneal microcysts was identified in a patient taking the antibody-drug conjugate mirvetuximab soravtansine and was reversible with topical steroids. A bilateral medium-vessel choroidal vasculopathy with serous retinal detachment was seen with ipilimumab. The most frequent medication with ocular toxicity was interferon-α(2b) (IFN-α(2b)) (6/31, 19.4%); headache was typical in these patients (83.3%). Ibrutinib ocular toxicity was second most common (5/31, 16.1%), usually causing red or dry eye, while one patient developed branch retinal artery occlusion. Retinal abnormalities documented on OCT imaging occurred with IFN-α(2b), ipilimumab, binimetinib, and docetaxel, while rod-cone ERG abnormality was seen with cisplatin. Inflammatory conditions included anterior scleritis with zoledronic acid, focal eyelid inflammation with veliparib, bilateral chemosis with R-CHOP, iritis, and blepharospasm with IFN-α(2b). AION occurred with pemetrexed, and transient vision loss with hyperemic disc OS was seen with FOLFOX. Two patients (2/31, 6.5%) developed permanent vision loss. Six patients were lost to follow-up, and the clinical course was unknown (6/31, 19.4%).
Cases of permanent visual loss were observed; yet, in the majority of side effects, they improved with topical therapy and/or holding the medication. Further research is needed to elucidate the incidence and the pathophysiology of these side effects and maximize patient quality of life.
随着人口老龄化导致癌症发病率上升以及新型化疗药物的迅速发展，凸显了眼科医生识别和管理潜在眼部毒性的必要性。本回顾性病例系列报告了来自一个大型中心的传统和新型化疗药物的眼部副作用。
回顾了2010年1月至2015年2月期间到学术眼科部门就诊的3537名18岁及以上成年患者的病历，这些患者因ICD - 9搜索确定的高风险药物而前来就诊。纳入研究需要有癌症诊断，以及与化疗使用和眼部副作用的时间关联。主要指标是接受化疗的癌症患者的眼部副作用、眼部影像学异常以及每种副作用的结果。
在转诊至眼科诊所进行化疗筛查或眼部副作用评估的161名肿瘤患者中，31名（19.3%）被确定因新型或传统化疗药物出现眼部不良反应。一名服用抗体药物偶联物米尔维妥昔单抗索拉坦辛的患者出现了角膜曲率新的变平伴远视移位和角膜微囊肿，局部使用类固醇后可逆转。使用伊匹单抗时可见双侧中血管脉络膜血管病变伴浆液性视网膜脱离。眼部毒性最常见的药物是干扰素-α(2b)（IFN-α(2b)）（6/31，19.4%）；这些患者中头痛很典型（83.3%）。伊布替尼的眼部毒性次之（5/31，16.1%），通常导致眼红或眼干，而一名患者发生了视网膜分支动脉阻塞。IFN-α(2b)、伊匹单抗、比美替尼和多西他赛治疗时在OCT成像上记录到视网膜异常，而顺铂治疗时可见视杆 - 视锥细胞ERG异常。炎症情况包括唑来膦酸引起的前巩膜炎、维利帕尼引起的局灶性眼睑炎症、R - CHOP引起的双侧结膜水肿、虹膜炎以及IFN-α(2b)引起的眼睑痉挛。培美曲塞治疗时发生前部缺血性视神经病变（AION），FOLFOX治疗时出现视盘充血伴短暂视力丧失。两名患者（2/31，6.5%）出现永久性视力丧失。6名患者失访，临床病程不明（6/31，19.4%）。
观察到了永久性视力丧失的病例；然而，在大多数副作用中，通过局部治疗和/或停药后症状有所改善。需要进一步研究以阐明这些副作用的发生率和病理生理学，并使患者生活质量最大化。
