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高剂量羟氯喹对慢性移植物抗宿主病患者的视网膜毒性

Retinal toxicity of high-dose hydroxychloroquine in patients with chronic graft-versus-host disease.

作者信息

Navajas Eduardo V, Krema Hatem, Hammoudi Dena S, Lipton Jeffrey H, Simpson E Rand, Boyd Shelley, Easterbrook Michael

机构信息

Department of Ophthalmology, Eye Care Centre, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada?>.

Department of Ophthalmology and Vision Sciences?>

出版信息

Can J Ophthalmol. 2015 Dec;50(6):442-50. doi: 10.1016/j.jcjo.2015.08.003.

Abstract

OBJECTIVE

To evaluate retinal toxicity in patients treated with high-dose hydroxychloroquine (HCQ) (Plaquenil, Sanofi Pharmaceuticals) for chronic graft-versus-host disease (GVHD).

DESIGN

Cohort study.

PARTICIPANTS

Twelve patients with chronic GVHD treated with 800 mg/day HCQ between June 2005 and December 2010.

METHODS

Patients in this study underwent ophthalmologic examination yearly and ancillary studies including colour vision, Amsler grid, fundus photographs, Humphrey 10-2 automated perimetry, spectral-domain optical coherence tomography (SD-OCT), and multifocal electroretinography (mfERG). Evidence of HCQ toxicity was determined by the presence of scotomas in the Amsler grid and Humphrey 10-2 automated perimetry, and confirmed by at least 1 objective test including SD-OCT or mfERG.

RESULTS

Of the 12 patients, 7 were male and 5 were female. Mean age was 49 years. Mean best corrected visual acuity at baseline was 20/25 and remained 20/25 at final follow-up. Median duration of HCQ treatment was 22.8 months. Median adjusted daily dosage was 11.5 mg/kg/day. Seven patients developed vortex keratopathy. No signs of pigmentary retinopathy or bull's-eye maculopathy were found in any of the patients. Three patients developed retinal toxicity with scotomas in the Amsler grid and Humphrey 10-2 automated perimetry, as well as abnormal mfERG. Retinal structure measured by SD-OCT was abnormal in 2 of the 3 patients with retinal toxicity. Colour vision measured by Ishihara plates, as well as by 100 Hue colour test, was abnormal in 2 of the 3 patients with retinal toxicity.

CONCLUSIONS

High-dose HCQ in patients with GVHD was associated with higher incidence and earlier development of retinal toxicity.

摘要

目的

评估接受高剂量羟氯喹(HCQ,商品名:纷乐,赛诺菲制药公司生产)治疗慢性移植物抗宿主病(GVHD)患者的视网膜毒性。

设计

队列研究。

参与者

2005年6月至2010年12月期间,12例接受每日800mg HCQ治疗的慢性GVHD患者。

方法

本研究中的患者每年接受眼科检查以及包括色觉、阿姆斯勒方格表、眼底照相、 Humphrey 10-2自动视野计、光谱域光学相干断层扫描(SD-OCT)和多焦视网膜电图(mfERG)在内的辅助检查。HCQ毒性的证据通过阿姆斯勒方格表和Humphrey 10-2自动视野计中暗点的存在来确定,并通过至少一项包括SD-OCT或mfERG在内的客观检查来证实。

结果

12例患者中,7例为男性,5例为女性。平均年龄为49岁。基线时平均最佳矫正视力为20/25,末次随访时仍为20/25。HCQ治疗的中位持续时间为22.8个月。调整后的每日中位剂量为11.5mg/kg/天。7例患者出现涡状角膜病变。所有患者均未发现色素性视网膜病变或靶心样黄斑病变的迹象。3例患者出现视网膜毒性,在阿姆斯勒方格表和Humphrey 10-2自动视野计中出现暗点,同时mfERG异常。3例视网膜毒性患者中有2例通过SD-OCT测量的视网膜结构异常。3例视网膜毒性患者中有2例通过石原氏色盲测试板以及100色相颜色测试测量的色觉异常。

结论

GVHD患者使用高剂量HCQ与视网膜毒性的较高发生率和较早发生有关。

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