Haliyur Rachana, Elner Susan G, Sassalos Therese, Kodati Shilpa, Johnson Mark W
From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center (R.H., S.G.E., T.S., S.K., M.W.J.), University of Michigan, Ann Arbor, Michigan, USA.
From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center (R.H., S.G.E., T.S., S.K., M.W.J.), University of Michigan, Ann Arbor, Michigan, USA.
Am J Ophthalmol. 2025 Apr;272:8-18. doi: 10.1016/j.ajo.2024.12.028. Epub 2025 Jan 3.
To summarize and categorize postulated mechanisms of immune checkpoint inhibitor (ICI)-mediated retinal and choroidal inflammation and discuss resulting implications for evaluation and management of these adverse reactions.
Targeted literature review with interpretation and perspective METHODS: We performed a review of selected literature describing immune-mediated retinal and choroidal adverse reactions associated with ICI therapy, synthesizing and categorizing the likely underlying pathogenic mechanisms. Based on these mechanistic categories, we provide perspective on a rational approach to the evaluation of patients with ICI-associated inflammatory disorders of the retina and choroid.
ICI-induced posterior segment adverse reactions can be categorized into 3 major mechanisms of unintended, targeted inflammation that share similarities to immunotherapy-related adverse events (irAEs) seen in other organ systems. In Type 1 reactions, T cell activation by ICIs can result in cross-reactivity of anti-tumor T cells with ocular tissues (Type 1a) or expansion of eye-specific T cells in predisposed individuals (Type 1b), leading to ocular inflammation that mimics known uveitic conditions. In Type 2 reactions, nonspecific ocular or systemic inflammation exacerbated by ICI use can cause retinal vasculitis through a "bystander" mechanism, potentially resulting in vision-threatening vascular occlusions. Finally, in Type 3 reactions, ICI use can prompt autoantibody-mediated inflammation and/or exacerbation of paraneoplastic processes likely related to T cell driven expansion of B cell populations.
Although relatively uncommon, posterior segment inflammatory disorders associated with systemic ICI therapy may be vision-threatening if not identified and treated appropriately. We propose that the pathogenic mechanisms underlying these chorioretinopathies falls into 3 major categories involving inadvertent T cell mediated inflammation. Visual prognosis with appropriate treatment is generally favorable, but some reactions, such as longstanding exudative retinal detachments and ICI-induced occlusive retinal vasculitis, can result in permanent visual defects.
总结并分类免疫检查点抑制剂（ICI）介导的视网膜和脉络膜炎症的假定机制，并讨论这些不良反应的评估和管理的相关影响。
带有解释和观点的靶向文献综述
我们对描述与ICI治疗相关的免疫介导的视网膜和脉络膜不良反应的选定文献进行了综述，综合并分类了可能的潜在致病机制。基于这些机制类别，我们对评估患有ICI相关视网膜和脉络膜炎症性疾病的患者的合理方法提供观点。
ICI诱导的眼后段不良反应可分为3种主要的意外靶向炎症机制，这些机制与在其他器官系统中所见的免疫治疗相关不良事件（irAEs）相似。在1型反应中，ICI激活T细胞可导致抗肿瘤T细胞与眼组织发生交叉反应（1a型），或使易感个体中眼特异性T细胞扩增（1b型），从而导致模仿已知葡萄膜炎情况的眼部炎症。在2型反应中，ICI使用加剧的非特异性眼部或全身炎症可通过“旁观者”机制导致视网膜血管炎，可能导致威胁视力的血管闭塞。最后，在3型反应中，ICI使用可促使自身抗体介导的炎症和/或副肿瘤过程加重，这可能与T细胞驱动的B细胞群体扩增有关。
尽管相对不常见，但与全身ICI治疗相关的眼后段炎症性疾病如果未得到适当识别和治疗，可能会威胁视力。我们提出，这些脉络膜视网膜病变的致病机制可分为3大类涉及意外T细胞介导的炎症。适当治疗后的视觉预后通常良好，但一些反应，如长期渗出性视网膜脱离和ICI诱导的闭塞性视网膜血管炎，可导致永久性视觉缺陷。
