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

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.

• INCLUSION CRITERIA:

• Affected participants must be 18 years of age or older and have:
• History of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) or Sjogren's syndrome, and
• History of Plaquenil(R) use, and
• Evidence of Plaquenil(R)-induced retinal toxicity, based on clinical findings.

• Unaffected volunteers must be 18 years of age or older and have:
• History of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) or Sjogren's syndrome, and
• History of Plaquenil(R) use, and
• No retinal disease upon examination within the last six months.

• All participants must be able to:
• Provide their own consent, and
• Safely provide a blood sample.

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Exclusion criteria

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(R) 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.