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

Plaquenil或羟氯喹及其相关化合物氯喹长期以来被鉴定为与视网膜毒性相关。这种毒性很少发生（在0.5-3.5%的药物患者中），但是，尽管如此，它仍然是一个问题，因为对视网膜的毒性即使不是完全不可逆，也是大部分不可逆的，并且这种毒性的视觉后遗症可能是毁灭性的。 已提出ABCA 4基因突变与Plaquenil毒性发展之间的关系。 如果ABCA 4突变或其他基因突变与Plaquenil毒性之间的关系被确定，这将使个性化医疗的实践成为可能。个性化医疗的实践得到了美国国会法案的支持，并利用基因测序获得的知识来定制个人医疗保健。因此，考虑使用羟氯喹或氯喹治疗的患者需要进行基因突变（如ABCA 4突变）的基因筛查，以便在实施治疗之前确定对该药物毒性作用非常敏感的患者。 本研究的目的是确定基因突变，从分析ABCA 4突变开始，可能与Plaquenil毒性相关，并将这些与参与者表型相关。 本研究将招募30名Plaquenil诱导的视网膜毒性患者和至少60名对照参与者参与本研究。 这是一项观察性研究，需要在受试者方便的时间段内（不超过两年）到NIH临床中心或当地眼科医生办公室进行1-2次门诊访视。 在收集了完整的医疗，家庭和手术史后，参与者将进行标准的身体和眼睛检查。眼部检查将包括散瞳眼底检查。非侵入性眼科检查（例如，视野测试、OCT、照片和自发荧光）。将拍摄照片（眼科）以记录Plaquenil毒性。参与者将抽取30 cc血液样本进行遗传分析。 在本财政年度，该方案已获得IRB批准，并已开始招募患者。 已开发并使用电子病历表存储作为本方案一部分收集的临床数据。 与加州圣地亚哥大学Ayyagaris博士实验室的合作将提供测序和确定患者DNA样本中检测到的任何突变的重要性的专业知识。 我们已招募受试者，并将继续在NEI招募受试者参加本研究。

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. We have enrolled participants and continue to enroll participants into this study at the NEI.