Chartrand Nicholas A, Lau Chap-Kay, Parsons Mark T, Handlon Jaiden J, Ronquillo Yasmyne C, Hoopes Phillip C, Moshirfar Majid
College of Medicine Phoenix, University of Arizona, Phoenix, Arizona, USA.
Hoopes Vision Research Center, Hoopes Vision, Draper, Utah, USA.
J Ocul Pharmacol Ther. 2023 Jan-Feb;39(1):3-16. doi: 10.1089/jop.2022.0094. Epub 2022 Nov 21.
In rare cases, bisphosphonates are well established to cause ocular inflammation, presenting as uveitis, episcleritis, scleritis, orbital inflammation, and/or conjunctivitis. Some reports of bisphosphonate-associated neuro-ophthalmic complications also exist. We identified 101 reports in the literature relating to bisphosphonate-associated ocular complications. In a great majority of cases, symptoms resolve after discontinuation of the drug and anti-inflammatory treatment. Many cases recur if rechallenged with the same bisphosphonate. First-generation nonamino bisphosphonates, including clodronate and etidronate, are not associated with ocular inflammation. Only 2nd- and 3rd-generation amino bisphosphonates, including pamidronate, alendronate, risedronate, ibandronate, and zoledronate are associated with these complications. The mechanism of bisphosphonate-induced ocular inflammation may be related to activation of γ/δ T cells or M1 macrophages. Intravenous forms, such as pamidronate and zoledronate, tend to have higher rates and faster onset of ocular inflammation, generally presenting within days of infusion. In oral bisphosphonates, such as alendronate and risedronate, these complications present with more sporadic timing. Rates of complications are also higher when bisphosphonates are used for malignancy, as doses tend to be higher compared with doses for osteoporosis.
在罕见情况下，双膦酸盐已被充分证实可引起眼部炎症，表现为葡萄膜炎、巩膜外层炎、巩膜炎、眼眶炎症和/或结膜炎。也有一些关于双膦酸盐相关神经眼科并发症的报道。我们在文献中确定了101篇与双膦酸盐相关眼部并发症有关的报告。在绝大多数情况下，停药并进行抗炎治疗后症状会缓解。如果再次使用相同的双膦酸盐，许多病例会复发。第一代非氨基双膦酸盐，包括氯膦酸盐和依替膦酸盐，与眼部炎症无关。只有第二代和第三代氨基双膦酸盐，包括帕米膦酸盐、阿仑膦酸盐、利塞膦酸盐、伊班膦酸盐和唑来膦酸盐与这些并发症有关。双膦酸盐诱导眼部炎症的机制可能与γ/δ T细胞或M1巨噬细胞的激活有关。静脉注射形式，如帕米膦酸盐和唑来膦酸盐，往往眼部炎症发生率更高且发病更快，通常在输注后数天内出现。在口服双膦酸盐，如阿仑膦酸盐和利塞膦酸盐中，这些并发症的发生时间更分散。当双膦酸盐用于治疗恶性肿瘤时，并发症发生率也更高，因为与用于治疗骨质疏松症的剂量相比，其剂量往往更高。
