Periman Laura M, Mah Francis S, Karpecki Paul M
Periman Eye Institute, Seattle, WA, USA.
Scripps Health, La Jolla, CA, USA.
Clin Ophthalmol. 2020 Dec 2;14:4187-4200. doi: 10.2147/OPTH.S279051. eCollection 2020.
Dry eye disease (DED) is a multifactorial disease of the ocular surface and tear film that has gained awareness as a public health problem. Characteristics of DED include tear film instability, hyperosmolarity, and ocular surface inflammation, which can occur independently or may be a sequela of numerous ocular diseases, ocular surgery or contact lens wear. Much has been learned about the impact of the disease to help affected individuals who report symptoms of poor vision, pain, and tearing. Recently, new research highlights the importance of the role of ocular surface inflammation and damage in DED-leading to a vicious cycle of inflammation as well as loss of tear film homeostasis. DED immunopathophysiology is characterized by four stages: initiation, amplification, recruitment, and re-initiation. Cyclosporine is proven to be a valuable ophthalmic therapeutic for DED through its immunomodulatory actions and regulation of the adaptive immune response. Cyclosporine mechanism of action is well described in the published literature and the myriad of benefits in all four stages lend a broad-based immunomodulatory function particularly suitable for addressing DED. Furthermore, cyclosporine has unique goblet cell density improvement capabilities as well as anti-apoptotic properties. Topical formulations of cyclosporine are centered around addressing the highly lipophilic nature of the molecule. The poor aqueous solubility of cyclosporine traditionally presented technical challenges in drug delivery to the ocular surface. Newer formulations such as cationic emulsions and nanomicellar aqueous solutions address formulation, tissue concentration, and drug delivery challenges.
干眼疾病（DED）是一种眼表和泪膜的多因素疾病，已成为一个公共卫生问题而受到关注。DED的特征包括泪膜不稳定、高渗性和眼表炎症，这些情况可能独立出现，也可能是多种眼部疾病、眼科手术或佩戴隐形眼镜的后遗症。关于该疾病的影响我们已经了解很多，以帮助那些报告视力差、疼痛和流泪症状的患者。最近，新的研究强调了眼表炎症和损伤在DED中的作用的重要性——导致炎症的恶性循环以及泪膜稳态的丧失。DED的免疫病理生理学具有四个阶段：起始、放大、募集和重新起始。环孢素已被证明是一种对DED有价值的眼科治疗药物，通过其免疫调节作用和对适应性免疫反应的调节。环孢素的作用机制在已发表的文献中有详细描述，其在所有四个阶段的众多益处赋予了广泛的免疫调节功能，特别适合解决DED问题。此外，环孢素具有独特的改善杯状细胞密度的能力以及抗凋亡特性。环孢素的局部制剂主要围绕解决该分子的高亲脂性。环孢素传统上较差的水溶性在向眼表给药方面带来了技术挑战。新型制剂如阳离子乳液和纳米胶束水溶液解决了制剂、组织浓度和药物递送方面的挑战。
