GenotypeNCT01145196
Genotype-Phenotype Study of Patients With Plaquenil -Induced Retinal Toxicity, With Evaluation of the ABCA4 Gene
An observational study of Genotype and Retinal Disease, run by National Eye Institute (NEI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Genotype, Retinal Disease
- How many people
- 320 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Aug 2010to not given
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Show all 12Show fewer
- 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>
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Genotype, Retinal Disease
- Keywords
- Retinal Disease, Plaquenil-Induced, Natural History
- Medical subject headings
- Retinal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Affected | Participants affected by Plaquenil induced retinal toxicity | |
| Unaffected | control participants without Plaquenil induced retinal toxicity |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
The secondary outcome of this study is to determine the utility of various testing metrics in evaluating the presence of retinal toxicity.
Measured: annually for five years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2010 (estimated)
- Study start23 Aug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for GenotypeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 320 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Eye Institute (NEI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Emily Y Chew, M.D., Principal investigator, National Eye Institute (NEI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01145196
- Sponsor's protocol ID
- 100140
- Other IDs
- 10-EI-0140
- Status last verified
- 23 Sep 2026
- First submitted
- 15 Jun 2010
- Last updated
- 5 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 9259429HOBBS 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.
PubMed 14402143Webster 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.
PubMed 11328725
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genotype - Phenotype Study of Patients With Plaquenil-induced Retinal Toxicity
- ClinicalTrials.gov ID
- NCT01145196
- Acronym / sponsor ID
- 100140
- Conditions
- Genotype, Retinal Disease
- Keywords
- Retinal Disease, Plaquenil-Induced, Natural History
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 320 participants (estimated)
- Lead sponsor
- National Eye Institute (NEI)US National Institutes of Health
- Study start
- 23 Aug 2010 (actual)
- First posted
- 16 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Affected | – | –Participants affected by Plaquenil induced retinal toxicity |
| Unaffected | – | –control participants without Plaquenil induced retinal toxicity |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (12 listed)
- 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.
- History of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) or Sjogren's syndrome, and
- History of Plaquenil(R) use, and
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
Time frame: annually for five years
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.
1 secondary outcome
The secondary outcome of this study is to determine the utility of various testing metrics in evaluating the presence of retinal toxicity.
Time frame: annually for five years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Background: PubMed 9259429Levy 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.
- Background: PubMed 14402143HOBBS 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.
- Background: PubMed 11328725Webster 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Emily Y Chew, M.D. principal investigator
National Eye Institute (NEI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Genotype and Retinal Disease, run by National Eye Institute (NEI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Faith F Chen ((301) 402-1369, chenfa@nei.nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: annually for five years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01145196, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.