Genotype - phenotype Study of Patients with Plaquenil^-induced Retinal Toxicity,

普拉奎尼，或羟基氯喹，及其相关化合物氯喹，长期以来一直被发现与视网膜毒性有关。这种毒性很少发生(在服用该药物的患者中占0.5%-3.5%)，但尽管如此，它仍然是一个令人担忧的问题，因为对视网膜的毒性即使不是完全不可逆转的，也是不可逆的，这种毒性的视觉后遗症可能是毁灭性的。已经提出ABCA4基因突变与普莱奎尼毒性发生之间的关系。如果ABCA4突变或其他基因突变与普莱奎利毒性之间的关系被确定，这将使个性化药物的实践成为可能。个性化医疗的实践得到了美国国会一项法案的支持，并利用通过基因测序获得的知识来定制个人医疗服务。因此，考虑接受羟氯喹或氯喹治疗的患者将接受基因突变的基因筛查，例如ABCA4突变，以便在实施治疗之前确定对这种药物的毒性作用非常敏感的患者。 这项研究的目的是从分析ABCA4突变开始，识别可能与普莱奎利毒性相关的基因突变，并将这些突变与参与者的表型相关。这项研究将招募30名普乐奎尼引起的视网膜毒性患者和至少60名对照组参与者参与这项研究。这是一项观察性研究，要求患者在方便的时间内前往美国国立卫生研究院临床中心或当地眼科医生办公室就诊1-2次，时间不超过两年。在收集了完整的内科、家族史和手术史后，参与者将进行标准的身体和眼睛检查。眼科检查将包括眼底扩张检查。可以执行非侵入性眼科测试(例如，视野测试、OCT、照片和自发荧光)。将拍摄(眼科)照片以记录普莱奎利的毒性。参与者将抽取30毫升的血液样本进行基因分析。 在本财政年度，该方案获得了IRB的批准，并开始招募患者。已经开发了一种电子病历表格，并将其用于存储作为该方案的一部分收集的临床数据。与加州大学圣地亚哥分校的Ayyagaris博士实验室的合作，将提供在对患者DNA样本中检测到的任何突变进行测序和确定其重要性方面的专业知识。

Plaquenil, or hydroxychloroquine, and its related compound chloroquine, has long been identified to be associated with a retinal toxicity. This toxicity occurs rarely (in the range of 0.5-3.5% of patients on the drug), but, nevertheless, it remains a concern as the toxicity to the retina is mostly, if not wholly, irreversible and the visual sequelae from this toxicity can be devastating. A relationship has been proposed between mutations in the ABCA4 gene and the development of Plaquenil toxicity. If a relationship between ABCA4 mutations, or other genetic mutations, and Plaquenil toxicity is identified this would enable the practice of personalized medicine. The practice of personalized medicine is supported by a bill from the US congress and utilizes the knowledge gained by genetic sequencing to tailor an individuals medical care. It would follow that patients considered for hydroxychloroquine or chloroquine therapy undergo genetic screening for genetic mutations, such as ABCA4 mutations, so that patients who would be exquisitely sensitive to toxic effects of this drug are identified before the treatment is implemented. The objective of this study is to identify genetic mutations, starting with an analysis of ABCA4 mutations, that may be correlated with Plaquenil toxicity and correlate these with the participants phenotypes. This study will recruit 30 patients with Plaquenil-induced retinal toxicity and at least 60 control participants to participate in this study. This is an observational study that requires 1-2 outpatient visits to the NIH Clinical Center or a local ophthalmologists office over a period of time convenient to the participants, not to exceed two years. After gathering a complete medical, family and surgical history, participants will have standard physical and eye examination. The eye examination will include a dilated fundus examination. Non-invasive ophthalmologic testing (e.g., visual field testing, OCT, photos, and autofluorescence) may be performed. Photographs (ophthalmic) will be taken to document the Plaquenil toxicity. Participants will have a 30 cc blood sample drawn for genetic analysis. During this fiscal year, the protocol has gained IRB-approval and recruitment of patients has started. An electronic medical record form has been developed and utilized to store clinical data collected as part of this protocol. The collaboration with Dr. Ayyagaris lab at University of California San Diego will provide the expertise in sequencing and determining the significance of any mutations detected in the patients DNA samples.