Toxicity and efficacy of type I interferons on the ocular surface: in vitro, animal, and clinical studies

Abstract

Purpose: To investigate the toxicity of type I interferons (IFNs) on the ocular surface and assess their efficacy in ocular surface tumors. Methods: We examined the effects of IFN-alpha 2a, IFN-alpha 2b and IFN-beta on corneal epithelial cells and stromal fibroblasts in vitro as well as the impact of IFN-alpha 2a on the ocular surface in mice. Additionally, we analyzed the therapeutic and adverse effects of topically administered IFN-alpha 2a and IFN-alpha 2b in patients with ocular surface tumors. Risk factors contributing to side effects were explored. Results: IFN-alpha 2a, IFN-alpha 2b or IFN-beta 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-alpha 2a injection did not induce corneal epithelial defects or opacity, nor did it reduce aqueous tears or conjunctival goblet cells. In patients, topical IFN-alpha 2a or IFN-alpha 2b 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. Conclusion: 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.