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

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.
* Both individuals who have and have not developed plaquenil-induced retinal toxicity will be eligible for this study.

Design:

* The study requires one or two visits to the National Eye Institute or an outpatient study clinic over a maximum 2-year period.
* Participants will provide a personal and family medical history, and will have a full eye examination.
* Participants will also provide blood samples for testing.
* No treatment will be provided as part of this protocol.

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 Sj(SqrRoot)(Delta)gren s syndrome and history of Plaquenil(R) use, but without evidence of retinal toxicity, will also be recruited.

DESIGN:

The study is an observational study with 1-2 outpatient visits to the NEI clinic or review of medical records for off-site participants. All participants will provide a blood sample for genetic analysis.

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:
-INCLUSION CRITERIA:

1. Affected participants must be 18 years of age or older and have:

   * History of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) or Sj(SqrRoot)(Delta)gren s syndrome, and
   * History of Plaquenil use, and
   * Evidence of Plaquenil -induced retinal toxicity, based on clinical findings.
2. Unaffected volunteers must be 18 years of age or older and have:

   * History of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) or Sj(SqrRoot)(Delta)gren s syndrome, and
   * History of Plaquenil use, and
   * No retinal disease upon examination within the last six months.
3. All participants must be able to:

   * Provide their own consent, and
   * Safely provide a blood sample.

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EXCLUSION CRITERIA:

1. Participants with other known (genetic) retinal disease including but not limited to: Stargardt s disease and cone or cone-rod dystrophy whose diagnosis preceded their Plaquenil use. Participants with no known previous genetic diagnosis but with clinical findings associated with a genetic diagnosis, such as parafoveal or macular flecks which are associated with Stargardt s disease or fundus flavimaculatus, will also be excluded.