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病例报告

阿伦膦酸盐是一种新型的双膦酸盐，主要用于治疗骨质疏松症和其他几种骨疾病。在此我们报告一个病例显示急性视网膜色素上皮炎(ARPE)后口服阿仑膦酸由于骨质疏松。一位50岁的女性病人向我们报告她的左眼视力模糊和变视。既往未见眼损害报告。除了口服阿仑膦酸治疗骨质疏松6个月外，她没有任何系统性疾病的临床病史。视力分别为20/40 OS和20/20 OD。未见玻璃体炎或前葡萄膜炎。眼底检查显示OS视网膜色素上皮(RPE)黄斑周围有一淡色的低色素晕，周围有轻微的色素沉着块。右眼眼底镜显示在中央凹上方有一簇不规则的色素沉着，并在其周围有轻微的色素沉着。荧光素血管造影(FA)显示早期低荧光的不规则斑片状区域，被高荧光包围，而在晚期消退(图1A)。 Early-phase and midphase indocyanine green angiography (ICG) showed a patchy macular hypofluorescence in both eyes (Figures 1B and 1C). Similar disseminated spots of hypofluorescence were shown at the periphery nasally to the optic disk; hypofluorescent halo with a petaloid like appearance of the macular area was observed in OS on late ICG. Patient discontinued treatment with alendronate. She underwent weekly ocular examination up to 4 weeks. Her symptoms improved in OS with VA of 20/20 in 1 week after discontinuation. FA and ICG revealed some patched areas of irregular hypofluorescence surrounding the old spots due to filling defect of choroidal vessels and characterized by late staining of dye on FA and no leakage (Figures 2A and 2B). Hypofluorescent areas were shown on both intermediate and late ICG phases with reducing size compared to the acute phases in the same areas.

图1所示。荧光素血管造影显示早期hypofluorescence hyperfluorescent光环包围的多个景点,位于后极OS (A)。早期和晚期阶段的吲哚菁绿血管造影(ICG)显示弥漫性hypofluorescent点与多个hypofluorescent点鼻双眼视神经乳头。ICG晚期(B, C)， OS黄斑区可见瓣状低荧光晕。

图2。停药4周后荧光素和吲哚青绿血管造影显示视网膜色素上皮水平活动性炎症灶逐步消退，晚期染色无渗漏(A, B)。

急性视网膜色素上皮炎(ARPE)，又称磷虾病，是一种年轻健康成人急性严重视力丧失的疾病，其病程自限性，男女均受影响[1]。它被认为代表了RPE炎症区域的色素上皮屏障的破坏和随后的浆液渗漏。我们报告一个病例，在长期口服阿仑膦酸后发生ARPE。这些副作用可以通过停止治疗来解决。许多药物包括各种形式的给药，包括外用制剂、眼周和眼内注射以及全身药物，都与葡萄膜炎有关。双磷酸盐主要用于治疗骨质疏松症。它们一般耐受性良好，即使这类药物中有几种与葡萄膜炎或其他眼部副作用有关[3]。双膦酸盐具有特别强的眼部毒性，包括眼眶炎症、巩膜炎、葡萄膜炎和AMD[4]。反过来，二磷酸盐被认为是促炎的。具体来说，它们通过激活T淋巴细胞和上调全身炎症标志物，如c -反应蛋白、白细胞介素-6和白细胞介素-8[5]，启动炎症级联。 In our report we consider ARPE as an adverse reaction to biphosphonate, even though a casual effect could not be ruled out. There was a time relation between both administration and discontinuation of the drug in absence of other drugs or chemicals or of concurrent disease that could explain the ocular side effect. A similar case has been reported, but conversely to our case symptoms begun early 1 month following intravenous infusion of biphosphonate (zoledronate). Also in our case a well-documented angiographic examination was carried out with both FA e ICG, showing the acute and subacute/chronic effects of ARPE secondary to oral biphosphonate administration. Drug-induced ocular side-effects is well-recognized and observed with a broad range of medications. A detailed drug history should be elicited, therefore, in all patients with otherwise unexplained symptoms. It is important that ocular symptomatology occurring in association with the use of novel medicines is diagnosed and data drawn to the attention of physicians, even though other reports are required to confirm such findings.

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所有作者证明，他们与任何组织或实体没有任何关联或参与与任何经济利益，或非经济利益的主题或材料在本手稿中讨论。所有作者都参与了研究的设计和实施，数据的收集、管理、分析和解释，手稿的准备、审查和批准。

参考文献

1. 急性视网膜色素上皮炎。是J角膜切削74: 193 - 205。
2. Wysowski DK, Greene P(2013) 2002-2012年美国口服和静脉注射双膦酸盐治疗骨质疏松的趋势。骨57: 423 - 428。(Crossref)
3. Etminan M, Forooghian F, Maberley D(2012)口服双膦酸盐的眼部炎症不良事件:一项回顾性队列研究。医疗协会184: E431-E434。(Crossref)
4. mamo Z, Guo M, Maberley D, Matsubara J, Etminan M(2016)口服双磷酸盐与湿性年龄相关性黄斑变性的风险。是J角膜切削168: 62 - 67。(Crossref)
5. Hewitt RE, Lissina A, Green AE, Slay ES, Price DA, et .(2005)双膦酸盐急性期反应:他汀类药物抑制了对氨基双膦酸盐反应时外周血gd T细胞快速和大量产生促炎细胞因子。中国Exp Immunol139: 101 - 111。(Crossref)