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

Genotype - Phenotype Study of Patients With Plaquenil-induced Retinal Toxicity

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.

Study Overview

• Status: Recruiting
• Conditions: Retinal Disease; Genotype

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.

• Study Type: Observational
• Enrollment (Estimated): 320

Contacts and Locations

• Study Contact: Name: Emily Y Chew, M.D.; Phone Number: (301) 496-6583; Email: echew@nei.nih.gov
• Study Contact Backup: Name: Faith F Chen; Phone Number: (301) 402-1369; Email: chenfa@nei.nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY dial 711 800-411-1222; Email: ccopr@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

• 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 Sjogren's syndrome, and
• History of Plaquenil(R) use, and

• Evidence of Plaquenil(R)-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 Sjogren's syndrome, and
• History of Plaquenil(R) 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.

<TAB>

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Affected; Participants affected by Plaquenil induced retinal toxicity
Unaffected; control participants without Plaquenil induced retinal toxicity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
The secondary outcome of this study is to determine the utility of various testing metrics in evaluating the presence of retinal toxicity.	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

Collaborators and Investigators

• Sponsor: National Eye Institute (NEI)
• Investigators: Principal Investigator: Emily Y Chew, M.D., National Eye Institute (NEI)

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2010

Study Registration Dates

• First Submitted: June 15, 2010
• First Submitted That Met QC Criteria: June 15, 2010
• First Posted (Estimated): June 16, 2010

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 11, 2026
• Last Verified: June 10, 2026

More Information

Terms related to this study

• Keywords: Natural History; Retinal Disease; Plaquenil-Induced
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases
• Other Study ID Numbers: 100140; 10-EI-0140

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No