氯喹和羟氯喹引起视网膜病变筛查…

氯喹和羟氯喹引起视网膜病变的2016版筛查建议

作者：Marmor MF, et al.
翻译：北医三院李常虹（changhongli@bjmu.edu.cn）
发布：孙琳
审核：姚中强


背景：鉴于药物毒性发生率、危险因素、眼底病变分布范围以及筛选工具效力方面的信息更新，美国眼科学会就氯喹和羟氯喹引起视网膜病变的筛查建议进行了重新修订。
视网膜病变的形式：尽管抗疟药引起的毒性反应主要发生在眼睛的中央凹周围，但是亚洲患者经常会出现一种黄斑以外的其他损害形式。剂量：我们推荐羟氯喹的每天最大用量应≤5.0毫克/公斤真实体重，且真实体重比理想体重与药物毒性发生风险更为相关。尚没有有关氯喹的类似这方面的人口统计资料，但先前的文献资料提示氯喹的每天最大用量应≤2.3毫克/公斤真实体重。
毒性风险：药物的毒性风险依赖于每日药物服用剂量和用药持续时间。使用推荐剂量的药物时，用药5年发生药物毒性的风险小于1%，用药10年发生药物毒性的风险小于2%，但用药20年发生药物毒性的风险差不多增加至20%。然而，对于用药20年后也未出现毒性反应的患者，在随后应用药物期间出现毒性反应的几率仅为4%。
主要的危险因素：大剂量、长疗程是最为重要的危险因素。其他的主要危险因素包括同时合并肾脏疾病或使用他莫西芬。
筛查时间表：基线时应行眼底检查以除外先前存在的黄斑病变。对于接受合适剂量且没有主要危险因素的患者应在5年后接受每年一次的筛查。
筛查试验：初步的筛查试验包括自动视野检查和光学相干层析成像。在亚洲患者中，筛查时应注意观察中心黄斑以外的视网膜区域。多焦视网膜电图可对视野进行客观的确证，眼底自发荧光可在形态上显示视网膜的病变部位。经过现代化的筛查试验应在肉眼发现眼底病变之前察觉视网膜病变。
毒性：视网膜病变是不可逆的，目前尚无治疗的办法。早期发现对于预防中心视力丧失十分重要。然而，对于可疑的检查结果应进行重复，或采取其他的试验进一步证实，以避免无辜中断有意义的治疗方案。
建议：患者（和处方医生）应被告知药物毒性的发生风险、合适的用药剂量以及规律筛查的重要性。

附原文 AbstractBACKGROUND: The American Academy of Ophthalmology recommendationson screening for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy arerevised in light of new information about the prevalence of toxicity, riskfactors, fundus distribution, and effectiveness of screening tools.PATTERN OF RETINOPATHY: Although thelocus of toxic damage is parafoveal in many eyes, Asian patients often show anextramacular pattern of damage. DOSE: We recommend a maximum daily HCQ use of≤5.0 mg/kg real weight, which correlates better with risk than ideal weight.There are no similar demographic data for CQ, but dose comparisons in olderliterature suggest using ≤2.3 mg/kg real weight.RISK OF TOXICITY: The risk of toxicity is dependent on daily doseand duration of use. At recommended doses, the risk of toxicity up to 5 yearsis under 1% and up to 10 years is under 2%, but it rises to almost 20% after 20years. However, even after 20 years, a patient without toxicity has only a 4%risk of converting in the subsequent year.MAJOR RISK FACTORS: High dose and long duration of use are themost significant risks. Other major factors are concomitant renal disease, oruse of tamoxifen.SCREENING SCHEDULE: Abaseline fundus examination should be performed to rule out preexistingmaculopathy. Begin annual screening after 5 years for patients on acceptabledoses and without major risk factors.SCREENING TESTS: The primary screening tests are automated visual fieldsplus spectral-domain optical coherence tomography (SD OCT).These should look beyond the central macula in Asian patients. The multifocalelectroretinogram (mfERG) can provide objective corroboration for visualfields, and fundus autofluoresce (FAF) can show damagetopographically. Modern screening should detect retinopathy before it isvisible in the fundus. TOXICITY: Retinopathyis not reversible, and there is no present therapy. Recognition at an earlystage (before any RPE loss) is important to prevent central visual loss.However, questionable test results should be repeated or validated withadditional procedures to avoid unnecessary cessation of valuable medication. COUNSELING: Patients (and prescribingphysicians) should be informed about risk of toxicity, proper dose levels, andthe importance of regular annual screening.

引自：Marmor MF,Kellner U, Lai TY, et al.American Academy of Ophthalmology. Recommendations on Screeningfor Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology. 2016 Jun;123(6):1386-94. doi:10.1016/j.ophtha.2016.01.058. Epub 2016 Mar 16.