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

NCT01145196 | Recruiting

• 2 other identifiers: 10014010-EI-0140
• Study Type: observational
• Target: 320
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Retinal Disease; Genotype

Keywords

Retinal Disease; Plaquenil-Induced; Natural History

Outcome Measures

Primary Outcomes (1)

• The 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 use.

  The 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 use.

  annually for five years

Secondary Outcomes (1)

• The secondary outcome of this study is to determine the utility of various testing metrics in evaluating the presence of retinal toxicity.

  annually for five years

Study Arms (2)

Affected

Participants affected by Plaquenil induced retinal toxicity

Unaffected

control participants without Plaquenil induced retinal toxicity

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study will enroll 100 patients, 18 years of age or older, found to have Plaquenil -induced retinal toxicity. 200 volunteers with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), or Sjogren's syndrome and history of Plaquenil use, but without evidence of retinal toxicity, will also be recruited.

You may qualify if:

• \. 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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You may not qualify if:

• 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.

Sponsors & Collaborators

• National Eye Institute (NEI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (3)

• Levy GD, Munz SJ, Paschal J, Cohen HB, Pince KJ, Peterson T. Incidence of hydroxychloroquine retinopathy in 1,207 patients in a large multicenter outpatient practice. Arthritis Rheum. 1997 Aug;40(8):1482-6. doi: 10.1002/art.1780400817.

  PMID: 9259429 BACKGROUND

• HOBBS HE, SORSBY A, FREEDMAN A. Retinopathy following chloroquine therapy. Lancet. 1959 Oct 3;2(7101):478-80. doi: 10.1016/s0140-6736(59)90604-x. No abstract available.

  PMID: 14402143 BACKGROUND

• Webster AR, Heon E, Lotery AJ, Vandenburgh K, Casavant TL, Oh KT, Beck G, Fishman GA, Lam BL, Levin A, Heckenlively JR, Jacobson SG, Weleber RG, Sheffield VC, Stone EM. An analysis of allelic variation in the ABCA4 gene. Invest Ophthalmol Vis Sci. 2001 May;42(6):1179-89.

  PMID: 11328725 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Retinal Diseases

Condition Hierarchy (Ancestors)

Eye Diseases

Study Officials

• Emily Y Chew, M.D.

  National Eye Institute (NEI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Faith F Chen

CONTACT

(301) 402-1369; chenfa@nei.nih.gov

Emily Y Chew, M.D.

CONTACT

(301) 496-6583; echew@nei.nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2010
• First Posted: June 16, 2010
• Study Start: August 23, 2010
• Last Updated: June 12, 2026

Record last verified: 2026-06-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)