To investigate the toxicity of type I interferons (IFNs) on the ocular surface and assess their efficacy in ocular surface tumors. We examined the effects of IFN-α2a, IFN-α2b and IFN-β on corneal epithelial cells and stromal fibroblasts as well as the impact of IFN-α2a on the ocular surface in mice. Additionally, we analyzed the therapeutic and adverse effects of topically administered IFN-α2a and IFN-α2b in patients with ocular surface tumors. Risk factors contributing to side effects were explored. IFN-α2a, IFN-α2b or IFN-β reduced cell viability and induced pro-inflammatory cytokines in corneal epithelial cells and stromal fibroblasts. Furthermore, IFNs enhanced the expression of major histocompatibility complex class II and CD40 in corneal epithelial cells. In mice, subconjunctival IFN-α2a injection did not induce corneal epithelial defects or opacity, nor did it reduce aqueous tears or conjunctival goblet cells. In patients, topical IFN-α2a or IFN-α2b administration decreased tumor size and prevented recurrence; however, it was associated with mild side effects, including corneal epitheliopathy and conjunctival hyperemia. These complications were associated with longer IFN use, the presence of underlying ocular surface disease and concurrent use of mitomycin C or anti-glaucoma eye drops. Although type I IFNs cause direct toxicity on corneal cells, they do not induce significant side effects on the healthy ocular surface. Considering its therapeutic and preventive effects, topical type I IFN is safe and effective for treating ocular surface tumors. The potential for ocular side effects should be considered in eyes with identified risk factors.

中文翻译：

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I 型干扰素对眼表的毒性和功效：体外、动物和临床研究


研究 I 型干扰素 (IFN) 对眼表的毒性并评估其对眼表肿瘤的疗效。我们研究了 IFN-α2a、IFN-α2b 和 IFN-β 对角膜上皮细胞和基质成纤维细胞的影响，以及 IFN-α2a 对小鼠眼表的影响。此外，我们还分析了局部给予 IFN-α2a 和 IFN-α2b 对眼表肿瘤患者的治疗和不良反应。探讨了导致副作用的风险因素。 IFN-α2a、IFN-α2b 或 IFN-β 降低角膜上皮细胞和基质成纤维细胞中的细胞活力并诱导促炎细胞因子。此外，IFN 增强了角膜上皮细胞中主要组织相容性复合物 II 类和 CD40 的表达。在小鼠中，结膜下注射 IFN-α2a 不会引起角膜上皮缺陷或混浊，也不会减少房水或结膜杯状细胞。在患者中，局部使用 IFN-α2a 或 IFN-α2b 可缩小肿瘤大小并预防复发；然而，它与轻微的副作用相关，包括角膜上皮病变和结膜充血。这些并发症与较长时间使用干扰素、存在潜在的眼表疾病以及同时使用丝裂霉素 C 或抗青光眼滴眼液有关。尽管 I 型干扰素对角膜细胞造成直接毒性，但它们不会对健康眼表产生明显的副作用。考虑到其治疗和预防作用，局部I型干扰素治疗眼表肿瘤是安全有效的。对于已确定危险因素的眼睛，应考虑潜在的眼部副作用。