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

NCT ID: NCT01145196

Last Updated: 2026-01-08

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 320 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2010-08-23

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.
• 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.

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 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.

Conditions

Genotype; Retinal Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Affected

Participants affected by Plaquenil induced retinal toxicity

No interventions assigned to this group

Unaffected

control participants without Plaquenil induced retinal toxicity

No interventions assigned to this group

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Eye Institute (NEI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emily Y Chew, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Eye Institute (NEI)

Locations

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Faith F Chen

Role: CONTACT

chenfa@nei.nih.gov

(301) 402-1369

Emily Y Chew, M.D.

Role: CONTACT

echew@nei.nih.gov

(301) 496-6583

Facility Contacts

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Role: primary

ccopr@nih.gov

800-411-1222 ext. TTY dial 711

References

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.

Reference Type: BACKGROUND

PMID: 9259429 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 14402143 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11328725 (View on PubMed)

Related Links

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2010-EI-0140.html

NIH Clinical Center Detailed Web Page

Other Identifiers

10-EI-0140

Identifier Type: -

Identifier Source: secondary_id

100140

Identifier Type: -

Identifier Source: org_study_id