Genotype-Phenotype Study of Patients With Plaquenil -Induced Retinal Toxicity, With Evaluation of the ABCA4 Gene

Summary

Background: \- Plaquenil (hydroxychloroquine) is an anti-inflammatory drug that is used to treat some autoimmune diseases such as lupus and rheumatoid arthritis. This drug can damage the retina by causing a condition called Plaquenil-induced retinal toxicity, which may lead to vision loss. However, most people taking Plaquenil do not develop this problem. Researchers are interested in studying whether differences in a person's genes explain why some people develop Plaquenil-induced retinal toxicity while others do not. Objectives: \- To investigate possible correlations between certain genes or genetic mutations and Plaquenil-induced retinal toxicity. Eligibility: * Individuals at least 18 years of age who have previously used Plaquenil. * History of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), or Sjogren's syndrome. * Both individuals who have and have not developed Plaquenil-induced retinal toxicity will be eligible for this study. Design: * The study requires five annual outpatient visits to the NIH Clinical Center. * Participants will provide a personal and family medical history, and will have a full eye examination. * Participants will also provide blood samples for genetic analysis, including whole exome and whole genome sequencing. * No treatment will be provided as part of this protocol.

Detailed Description

OBJECTIVE: The objective of this study is to investigate whether there is a correlation between genetic mutations, beginning with an analysis of ABCA4, and Plaquenil(R)-induced retinal toxicity and to describe the phenotype of Plaquenil(R)-induced retinal toxicity. STUDY POPULATION: The study will enroll 100 patients, 18 years of age or older, found to have Plaquenil(R)-induced retinal toxicity. 200 volunteers with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), or Sjogren's syndrome and history of Plaquenil(R) use, but without evidence of retinal toxicity, will also be recruited. DESIGN: The study is a longitudinal, observational study with five annual outpatient visits to the NEI clinic. All participants will provide a blood sample for genetic analysis, including whole exome or whole genome sequencing. OUTCOME MEASURES: Clinical examination and blood samples will be used for genetic testing and mutation identification. The primary outcome of this study is to identify genetic mutations, starting with those in ABCA4 gene, associated with retinal toxicity in participants with a history of Plaquenil(R) use. Secondary objectives include determining the utility of testing metrics in evaluating the presence of retinal toxicity.

Eligibility Criteria