Lu Louise J, Tsai James C, Liu Ji
Department of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, Connecticut.
Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York Eye and Ear Infirmary of Mount Sinai, New York, New York.
Yale J Biol Med. 2017 Mar 29;90(1):111-118. eCollection 2017 Mar.
Primary open-angle glaucoma (OAG) affects approximately 45 million people worldwide and more than 2.5 million people aged 40 years or older in the United States. Pharmacologic treatment for glaucoma is directed towards lowering intraocular pressure (IOP) to slow disease progression and delay visual field loss. Current medical treatment options for the lowering of IOP include the following classes of topical medications: beta-adrenergic antagonists, alpha-adrenergic agonists, cholinergic agonists, carbonic anhydrase inhibitors, and prostaglandin analogs. Issues with existing drugs include failure to achieve target IOP with monotherapy, drug-related side effects, and low patient compliance with multiple daily administration of eye drops. In recent years, the scientific and medical community has seen encouraging development of novel classes of drugs for primary OAG, the majority of which lower IOP by targeting the trabecular meshwork outflow pathway to increase aqueous humor outflow. Among the most promising new pharmacologic candidates are rho kinase inhibitors including ripasudil (K-115), netarsudil (AR-13324), and AMA0076; adenosine receptor agonists including trabodenoson (INO-8875); and modified prostaglandin analogs including latanoprostene bunod (LBN, BOL-303259-X) and ONO-9054. This study aims to systematically review and summarize the most recent developments in clinical trials for new pharmacologic options for the treatment of primary open-angle glaucoma.
原发性开角型青光眼(OAG)在全球约影响4500万人,在美国40岁及以上人群中超过250万人受其影响。青光眼的药物治疗旨在降低眼压(IOP)以减缓疾病进展并延缓视野丧失。目前降低眼压的药物治疗选择包括以下几类局部用药:β-肾上腺素能拮抗剂、α-肾上腺素能激动剂、胆碱能激动剂、碳酸酐酶抑制剂和前列腺素类似物。现有药物存在的问题包括单药治疗无法达到目标眼压、药物相关副作用以及患者对每日多次滴眼的依从性低。近年来,科学界和医学界在原发性开角型青光眼新型药物的研发方面取得了令人鼓舞的进展,其中大多数药物通过作用于小梁网流出途径来增加房水流出从而降低眼压。最有前景的新候选药物包括Rho激酶抑制剂,如ripasudil(K-115)、netarsudil(AR-13324)和AMA0076;腺苷受体激动剂,如trabodenoson(INO-8875);以及改良的前列腺素类似物,如拉坦前列素贝诺酯(LBN,BOL-303259-X)和ONO-9054。本研究旨在系统回顾和总结治疗原发性开角型青光眼新药物选择的临床试验的最新进展。