Sirbat D, Saudax E, Hurault de Ligny B, Hachet E, Raspiller A
J Fr Ophtalmol. 1983;6(10):829-36.
Flumequine (1 200 mg/day) was prescribed as treatment for infection of the urinary tract to three patients with chronic renal failure, who reported positive scotoma three days later. Ophthalmologic examination evinced bilateral symmetrical macular bullae. A characteristic yellow papule was present at foveal level. In all three cases, visual acuity was impaired (down to 4/10), without any angiographic alteration. Foveolas showed a moderate persistent hyperfluorescence. All patients recovered a normal visual acuity, within two days after treatment cessation, and bullae disappeared without sequelae within 5 days. The chronology and kinetics of clinical manifestations were clearly and reproducibly correlated with flumequine therapy in all patients, and suggest that this drug may be considered responsible for the ocular symptom reported. Chronic renal failure (creatinine clearance lower than 25 ml/mn) most certainly favoured the appearance of visual troubles, but other factors may possibly play a similar role: hepatic failure, individual hypersensitivity... Quinolones used as urinary antiseptics (nalidixic acid, oxolinic acid, pipemidic acid...), and other flumequine analogues may possibly be involved in such side-effects. This was reported by Bouissou et al. in an experimental model with nalidixic acid, where transient bullae appeared on young animals' articular cartilage. Such lesions are related to focal alterations of the C2 intermediary layer of cartilage, with marked edema of the interstitial material. The volume of synovial fluid increases concomitantly. These alterations suggest a direct cytotoxic effect at the intercellular level of target organs, a mechanism possibly also occurring in the retina.
氟甲喹(每日1200毫克)被用于治疗3例慢性肾衰竭患者的尿路感染,3天后这3例患者均报告出现阳性暗点。眼科检查显示双侧对称性黄斑大疱。在黄斑中心凹水平可见一个特征性黄色丘疹。在所有3例患者中,视力均受损(降至4/10),血管造影无任何改变。黄斑中心凹显示中度持续性高荧光。所有患者在停药后2天内视力恢复正常,大疱在5天内消失且无后遗症。在所有患者中,临床表现的时间顺序和动力学与氟甲喹治疗明显且可重复相关,提示该药物可能是所报告眼部症状的病因。慢性肾衰竭(肌酐清除率低于25毫升/分钟)很可能促使视觉问题出现,但其他因素可能也起类似作用:肝功能衰竭、个体超敏反应……用作尿路防腐剂的喹诺酮类药物(萘啶酸、奥索利酸、吡哌酸……)以及其他氟甲喹类似物可能也与此类副作用有关。布伊苏等人在萘啶酸的实验模型中报告了这一情况,在该模型中,幼龄动物的关节软骨上出现了短暂性大疱。此类病变与软骨C2中间层的局灶性改变有关,间质物质有明显水肿。滑液量随之增加。这些改变提示在靶器官的细胞间水平存在直接细胞毒性作用,视网膜可能也存在这一机制。