警惕长期服用羟氯喹患者的视网膜病变风险

警惕长期服用羟氯喹患者的视网膜病变风险

贾俊峰

2015-12-11

空军军医大学西京医院临床免疫科贾俊峰

重要性：

硫酸羟氯喹长期广泛用于治疗自体免疫疾病，但有引起不可逆的视网膜病变的毒性。以前对其危险性的估计较低，但都主要基于短期的使用者或严重的视网膜毒性（牛眼黄斑病变）。早期使用更敏感的筛查技术视网膜病变，其毒性可能会更高。

目的：

重新评估羟氯喹视网膜毒性的患病率及危险因素，并确定剂量水平，以促进安全使用的药物。

设计，设置，和参与者：

回顾性病例对照研究，根据药房记录，对约340万会员的综合卫生机构有连续使用羟氯喹为至少5年2361例患者，进行了视野检查评价和谱域光学相干断层扫描。

暴露：

使用羟氯喹至少5年。

主要结局和指标：

视网膜毒性如通过特定的视野丧失或视网膜变薄和感光体损坏，以及风险因素和患病的统计度量来确定。

结果：

真正的体重预测的风险比理想体重更好，并用于所有的计算。羟氯喹视网膜病变的患病率为7.5％，但因不同的日常用量（比值比，5.67; 95％CI，4.14-7.79为> 5.0毫克/公斤），和使用的时间（比值比，3.22; 95％CI，2.20 -4.70> 10岁）不同。每天用量为4.0～5.0毫克/公斤，前10年用药过程中，视网膜毒性的患病率仍然不到2％，但经过20多年的使用将上升到近20％。其他主要的风险因素包括：肾脏疾病（比值比，2.08; 95％CI，1.44-3.01）和枸橼酸他莫昔芬治疗（比值比为4.59; 95％CI，2.05-10.27）。

结论和相关性：

这些数据表明，羟氯喹视网膜病变比以前的认识更为常见，尤其是在高剂量和持续长时间使用时。这项研究确定虽然没有完全安全的剂量，每天食用5.0毫克/千克的真实体重或更小剂量与长达10年的低风险有关。了解这些数据和风险因素应该有助于医生处方羟氯喹的方式，将视力下降的可能性最小化。

备注：

我们需要对羟氯喹视网膜病变做更好的准备。

读后：虽然低剂量长期使用羟氯喹的眼毒性很小，但是其对眼睛的毒性是不可逆的，而且尚无针对性药物。对于筛查来说，视野检查最为敏感，OCT（光学相干断层扫描）检查最为特异。羟氯喹对于多种风湿病来说是重要的基础用药，随着其更广泛的使用，加强风湿科、眼科医生的协作及对患者的教育，对于及时发现羟氯喹眼毒性，保护视力具有重要意义。

文献来源：

JAMA Ophthalmol. 2014 Dec;132(12):1453-60.

The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.

Melles RB, Marmor MF.

IMPORTANCE:

Hydroxychloroquine sulfate is widely used for the long-term treatment of autoimmune conditions but can cause irreversible toxic retinopathy. Prior estimations of risk were low but were based largely on short-term users or severe retinal toxicity (bull's eye maculopathy). The risk may be much higher because retinopathy can be detected earlier when using more sensitive screening techniques.

OBJECTIVES:

To reassess the prevalence of and risk factors for hydroxychloroquine retinal toxicity and to determine dosage levels that facilitate safe use of the drug.

DESIGN, SETTING, AND PARTICIPANTS:

Retrospective case-control study in an integrated health organization of approximately 3.4 million members among 2361 patients who had used hydroxychloroquine continuously for at least 5 years according to pharmacy records and who were evaluated with visual field testing or spectral-domain optical coherence tomography.

EXPOSURE:

Hydroxychloroquine use for at least 5 years.

MAIN OUTCOMES AND MEASURES:

Retinal toxicity as determined by characteristic visual field loss or retinal thinning and photoreceptor damage, as well as statistical measures of risk factors and prevalence.

RESULTS:

Real body weight predicted risk better than ideal body weight and was used for all calculations. The overall prevalence of hydroxychloroquine retinopathy was 7.5% but varied with daily consumption (odds ratio, 5.67; 95% CI, 4.14-7.79 for >5.0 mg/kg) and with duration of use (odds ratio, 3.22; 95% CI, 2.20-4.70 for >10 years). For daily consumption of 4.0 to 5.0 mg/kg, the prevalence of retinal toxicity remained less than 2% within the first 10 years of use but rose to almost 20% after 20 years of use. Other major risk factors include kidney disease (odds ratio, 2.08; 95% CI, 1.44-3.01) and concurrent tamoxifen citrate therapy (odds ratio, 4.59; 95% CI, 2.05-10.27).

CONCLUSIONS AND RELEVANCE:

These data suggest that hydroxychloroquine retinopathy is more common than previously recognized, especially at high dosages and long duration of use. While no completely safe dosage is identified from this study, daily consumption of 5.0 mg/kg of real body weight or less is associated with a low risk for up to 10 years. Knowledge of these data and risk factors should help physicians prescribe hydroxychloroquine in a manner that will minimize the likelihood of vision loss.

Comment in

We need to be better prepared for hydroxychloroquine retinopathy.