乙肝病毒相关的肝细胞癌是一种严重放射治疗后的恶化病情，并且往往难以切除的肿瘤。这些患者通常需要进行免疫治疗以改善其预后。然而，目前仍缺乏关于治疗效果和安全性的充分了解。本文报道了一名接受atezolizumab-bevacizumab联合治疗的患者，其罹患无法手术切除的肝细胞癌后出现了角膜穿孔事件。 经过详细描述病例的临床特点、治疗方案和监测结果，我们发现： 该患者在接受atezolizumab-bevacizumab联合治疗后表现出肝细胞癌的稳定状况，并具有对治疗的一定反应。 然而，在治疗过程中，该患者突然出现视力模糊和剧烈疼痛等角膜穿孔症状。进一步检查发现，该患者的眼科指标异常，并出现角膜穿孔，需要进行紧急治疗。 我们认为atezolizumab-bevacizumab联合治疗在重症患者中可能导致角膜穿孔的发生，但原因尚不清楚。 以上结果提醒医生在乙肝病毒相关的肝细胞癌患者中密切监测眼科症状和指标的变化，以及及时发现和处理病情的恶化，从而最大限度地提高治疗效果并降低并发症的风险。
Corneal Perforation in a Patient Treated with Atezolizumab-Bevacizumab Combination Therapy for Unresectable Hepatocellular Carcinoma.
发表日期：2023 Sep 01
作者：
Majed S Alkharashi, Rakan S Al-Essa, Wael Otaif, Ibrahim Algorashi
来源：
Cell Death & Disease
摘要：
背景：免疫检查点抑制剂（ICIs）靶向程序性细胞死亡蛋白1（PD-1）或其配体PD-L1，是几种转移性恶性病症的主要治疗方法。ICIs与多种器官不良反应相关，统称为免疫相关不良反应（irAEs）。干眼、葡萄膜炎、眼肌无力和瘢痕性结膜炎是与ICIs相关的已经广泛认识的眼睛irAEs。病例报告：我们报告了一例69岁男性患者，在接受atezolizumab-bevacizumab联合治疗治疗不可切除的肝细胞癌三周后，出现了左眼剖面性、穿孔样角膜溃疡，伴有双侧严重眼表疾病。使用丙烯酸酯胶进行角膜粘合术，并结合使用眼睛胶片和暂时性眼睑缝合术密封角膜穿孔和改善眼表。在随后的随访中，角膜胶粘剂不稳定并脱落。因此，进行了穿透性角膜移植以挽救球并停止联合治疗。在随访8个月后，移植物保持清晰，眼表在双眼中明显改善。结论：与免疫调节剂相关的眼睛irAEs可能导致威胁视力的并发症。因此，肿瘤学家和眼科医生在多学科团队中的沟通对于及时发现和治疗与免疫治疗剂使用相关的任何眼睛相关的不良反应至关重要。
BACKGROUND Immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1 (PD-1), or its ligand PD-L1, are the mainstay treatment for several metastatic malignant conditions. ICIs are associated with multiple toxic adverse events affecting various organs, known collectively as immune-related adverse events (irAEs). Dry eye, uveitis, ocular myasthenia, and cicatrizing conjunctivitis are well-recognized ocular irAEs associated with ICIs. CASE REPORT We present a case of 69-year-old man who presented with paracentral, punch-out corneal perforation in the left eye, associated with bilateral severe ocular surface disease 3 weeks after receiving the second dose of atezolizumab-bevacizumab combination therapy for the treatment of unresectable hepatocellular carcinoma. Corneal gluing using cyanoacrylate glue was performed along with bandage contact lens application and temporary tarsorrhaphy to seal the corneal perforation and improve the ocular surface. On the subsequent follow-ups, the corneal glue was unstable and dislodged. Thus, penetrating keratoplasty was performed to salvage the globe along with holding the combination therapy. At the 8-month follow-up, the graft remained clear, and the ocular surface improved substantially in both eyes. CONCLUSIONS Ocular irAEs associated with immune-modulating agents can lead to vision-threatening complications. Therefore, communications between oncologists and ophthalmologists in a multidisciplinary team would be of utmost importance for early detection and timely management of any ocular-related adverse events associated with the use of immunotherapy agents.