Hydroxychloroquine RetinopathyNCT06035887
Novel ERG for Detection of Hydroxychloroquine Retinopathy
An observational study of Hydroxychloroquine Retinopathy, run by King's College Hospital NHS Trust at 1 site in United Kingdom.
Trial summary
The purpose of the study is to investigate novel electroretinography (ERG) devices in the detection of hydroxychloroquine retinopathy. Two devices (the RETEval full-field and flicker ERG and UTAS multifocal ERG) will be evaluated in this study, comparing device outputs to standard of care screening tests, in groups of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hydroxychloroquine Retinopathy
- What is being tested?
- Hand-Held Full-Field Skin-Electrode Electroretinography (Device to be evaluated) and Trolley-Mounted Multifocal Skin-Electrode Electroretinography (Device to be evaluated)
- How many people
- 140 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 31 May 2024to May 2026
- 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 years and older
- All sexes
- Adult, Older adult
Study population: Age- and sex-matched control group (n=35) On hydroxychloroquine without retinopathy (n=35) On hydroxychloroquine with possible retinopathy (n=35) On hydroxychloroquine with definite retinopathy (n=35)
Who may be able to join
- Age ≥18 years
- HCQ groups:
- HCQ use >5 years for patients without any high-risk factors, or >1 year in patients with one or more high-risk factors for HCQ retinopathy, namely: i. Dose >5mg/kg per day actual body weight (ABW) ii. Estimated glomerular filtration rate (eGFR) of <60mls/min/1.73m2 iii. Concomitant tamoxifen use
- Control group:
- No prior HCQ exposure
Who cannot join
- Cataract grade ≥3 of any subtype
- Recent cataract surgery within 4 weeks of recruitment
- Significant media opacity or corneal disease including, but not limited to, corneal oedema, corneal scarring, keratoconus, previous corneal transplants, severe keratoconjunctivitis sicca (requiring the use of topical serum, immunosuppressive or analogous therapy, or procedural treatment).
- Significant macular co-pathology including, but not limited to, macular degeneration, macular scarring, cystic macular oedema (for any reason), staphyloma.
- Inherited retinal and/or macular dystrophies including colour vision deficiencies
- Active or previous posterior uveitis or pan-uveitis
Show all 21Show fewer
- Aphakia
- High refractive error >6.00 dioptres
- Amblyopia
- Diabetes
- Retinal angiopathies including, but no limited to, retinal vein occlusion, retinal artery occlusion, ocular ischaemic syndrome, HIV retinopathy, Sickle cell disease, radiation retinopathy
- Visually significant surgical retinal disease including epiretinal membrane, macular hole, retinal detachment, retinal tear
- Previous retinal laser or intravitreal treatment
- Moderate or worse glaucoma
- Optic atrophy
- Photosensitive epilepsy
- Ungradable HCQ retinopathy screening images
- Periocular infection or rash (recruitment can be deferred until acute pathology has resolved)
- Unable or unwilling to undertake study activities
- Any active use or history of the following medications:
- Amiodarone Canthaxanthin Deferoxamine Digoxin Ethambutol Interferon-alpha Melatonin Nefazodone Sildenafil Vigabatrin Chloroquine Quinine
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
King's College Hospital
London, London, SE5 9RS
Dr Chan Ning Lee, channing.lee2@nhs.net
Ophthalmology research inbox, kch-tr.ophthalmologyresearch@nhs.net
About this study
Official title: A Feasibility Study Using Novel, Portable Electroretinography Devices to Detect Hydroxychloroquine Retinopathy
The purpose of the study is to investigate novel electroretinography (ERG) devices in the detection of hydroxychloroquine retinopathy. Two devices (the RETEval full-field and flicker ERG and UTAS multifocal ERG) will be evaluated in this study, comparing device outputs to standard of care screening tests, in groups of participants characterised by presence or absence of hydroxychloroquine-related retinopathy.
Read the detailed description
Hydroxychloroquine (HCQ) is a widely used drug used to treat disorders of inflammation in the body with up to 320,000 people estimated to be on this drug in the UK alone. Retinopathy due to HCQ is a significant problem, necessitating yearly screening which can only realistically take place in hospital eye units where funding and capacity constraints limit the provision of services.
Electroretinography is a non-invasive method of testing for eye retinal problems, which works by flashing light (in certain patterns and brightness) into eyes and measuring the electrical response through fine wires placed on the eye surface or behind the eyelid, and is considered by many authors to be a gold-standard test to detect HCQ retinopathy. Their use has been limited due to the high expertise required to undertake and interpret tests, limited availability of testing, and high test burden, however newer electroretinography devices have been developed by a company called LKC Technologies, which are faster to perform, use leads placed on the skin (rather than the eye surface) which are more comfortable, easier to use by healthcare technicians, and can be done without the need for dilating eyedrops. The two devices being tested in this study are:
- The RETEval = a handheld electroretinography testing device
- The UTAS multifocal ERG = a trolley-mounted electroretinography testing device
These innovations may make testing far easier to develop in both hospital eye service, and potentially even general settings such as outpatient clinics, general practices, and optometrists. This study aims to evaluate the performance of devices to detect and classify participants in 4 main groups:
- Normative control participants (n=35)
- Patients taking HCQ but without retinopathy (n=35)
- Patients taking HCQ with indeterminate features of retinopathy (also known as POSSIBLE retinopathy) (n=35)
- Patients taking HCQ with definite retinopathy
Device outputs will be analysed and compared with masked graded screening results (incorporating spectral-domain macular optical coherence tomography and autofluorescence as standard, taken on the same visit) to generate device- and device-output-specific sensitivities and specificities. If a signal is found, the feasibility outcomes from this study will inform the study methodology and timelines for a larger trial if necessary.
- Conditions
- Hydroxychloroquine Retinopathy
- Being tested
- Hand-Held Full-Field Skin-Electrode Electroretinography (Device to be evaluated), Trolley-Mounted Multifocal Skin-Electrode Electroretinography (Device to be evaluated), Spectral-Domain Optical Coherence Tomography (Standard of Care test), Macular Autofluorescence (Standard of Care test)
- Keywords
- Electroretinography, Diagnostic Evaluation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hand-Held Full-Field Skin-Electrode Electroretinography (Device to be evaluated)Diagnostic test
RETEval Complete hand-held electroretinogram
Trolley-Mounted Multifocal Skin-Electrode Electroretinography (Device to be evaluated)Diagnostic test
UTAS multifocal electroretinogram
Spectral-Domain Optical Coherence Tomography (Standard of Care test)Diagnostic test
Heidelberg Engineering Spectralis Spectral-Domain Optical Coherence Tomography (macular structural scan)
Macular Autofluorescence (Standard of Care test)Diagnostic test
Heidelberg Engineering Spectralis Autofluorescence imaging (macular structural image)
| Study group | Role | What they receive |
|---|---|---|
| Normative Controls | Age- and sex- matched normal controls Receives: Diagnostic Test: Hand-Held Full-Field Skin-Electrode Electroretinography (Device to be evaluated); Diagnostic Test: Trolley-Mounted Multifocal Skin-Electrode Electroretinography (Device to be evaluated); Diagnostic Test: Spectral-Domain Optical Coherence Tomography (Standard of Care test); Diagnostic Test: Macular Autofluorescence (Standard of Care test) | |
| On Hydroxychloroquine, NO retinopathy | Participants over 18 years on hydroxychloroquine without hydroxychloroquine-related retinopathy Receives: Diagnostic Test: Hand-Held Full-Field Skin-Electrode Electroretinography (Device to be evaluated); Diagnostic Test: Trolley-Mounted Multifocal Skin-Electrode Electroretinography (Device to be evaluated); Diagnostic Test: Spectral-Domain Optical Coherence Tomography (Standard of Care test); Diagnostic Test: Macular Autofluorescence (Standard of Care test) | |
| On Hydroxychloroquine, POSSIBLE retinopathy | Participants over 18 years on hydroxychloroquine with possible (indeterminate) hydroxychloroquine-related retinopathy Receives: Diagnostic Test: Hand-Held Full-Field Skin-Electrode Electroretinography (Device to be evaluated); Diagnostic Test: Trolley-Mounted Multifocal Skin-Electrode Electroretinography (Device to be evaluated); Diagnostic Test: Spectral-Domain Optical Coherence Tomography (Standard of Care test); Diagnostic Test: Macular Autofluorescence (Standard of Care test) | |
| On Hydroxychloroquine, DEFINITE retinopathy | Participants over 18 years on hydroxychloroquine with definite hydroxychloroquine-related retinopathy Receives: Diagnostic Test: Hand-Held Full-Field Skin-Electrode Electroretinography (Device to be evaluated); Diagnostic Test: Trolley-Mounted Multifocal Skin-Electrode Electroretinography (Device to be evaluated); Diagnostic Test: Spectral-Domain Optical Coherence Tomography (Standard of Care test); Diagnostic Test: Macular Autofluorescence (Standard of Care test) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The sensitivity and specificity of both devices to discriminate between NO, POSSIBLE and DEFINITE hydroxychloroquine retinopathy compared to standard screening tests
Primary Outcome
Measured: All tests required to determine sensitivity and specificity of both devices compared to standard retinal imaging will be completed in a single visit. Safety will be evaluated up to 1 week post-visit.
Secondary outcomes (3)
To compare the sensitivity and specificity of undilated versus dilated testing with the multifocal ERG device, for all categories of hydroxychloroquine retinopathy
Secondary Outcome
Measured: All tests required to determine this outcome will be completed at a single visit. Safety will be evaluated up to 1 week post-visit.
To determine the patient acceptability of both devices evaluated using standardised, study-specific questionnaires
Feasibility Outcome
Measured: All tests required to determine this outcome will be completed at a single visit. Safety will be evaluated up to 1 week post-visit.
To determine the proportion and recruitment rate of patients in each category of hydroxychloroquine retinopathy who consent to join this study.
Feasibility Outcome
Measured: All tests required to determine this outcome will be completed at a single visit. Safety will be evaluated up to 1 week post-visit.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2023
- Study start31 May 2024
- Primary completionMay 2026 (estimated)
- Study completionMay 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hydroxychloroquine RetinopathyStudies of the same condition, open and under way.
- More trials run by King's College Hospital NHS TrustThe sponsor's other registered studies.
- 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
- Other
- Time perspective
- Prospective
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- King's College Hospital NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- LUPUS UK, King's College Hospital Charity
- Responsible party
- Sponsor
- Investigators
- Professor Timothy L Jackson, Study chair, King's College Hospital NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06035887
- Sponsor's protocol ID
- IRAS 317611
- Status last verified
- Aug 2025
- First submitted
- 29 Aug 2023
- Last updated
- 6 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Lee CN, Wafa HA, Murphy G, Galloway J, Mahroo OA, Jackson TL. Novel electroretinography devices to detect hydroxychloroquine retinopathy: study protocol for a diagnostic accuracy and feasibility study. BMJ Open Ophthalmol. 2024 Dec 24;9(1):e001898. doi: 10.1136/bmjophth-2024-001898.
PubMed 39719323
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Feasibility Study Using Novel, Portable Electroretinography Devices to Detect Hydroxychloroquine Retinopathy
- ClinicalTrials.gov ID
- NCT06035887
- Acronym / sponsor ID
- IRAS 317611
- Conditions
- Hydroxychloroquine Retinopathy
- Keywords
- Electroretinography, Diagnostic Evaluation
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- King's College Hospital NHS TrustUniversity, hospital or other
- Collaborators
- LUPUS UK, King's College Hospital Charity
- Study start
- 31 May 2024 (actual)
- Primary completion
- May 2026 (estimated)
- Study completion
- May 2026 (estimated)
- First posted
- 13 Sep 2023 (actual)
- 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.
The purpose of the study is to investigate novel electroretinography (ERG) devices in the detection of hydroxychloroquine retinopathy. Two devices (the RETEval full-field and flicker ERG and UTAS multifocal ERG) will be evaluated in this study, comparing device outputs to standard of care screening tests, in groups of participants characterised by presence or absence of hydroxychloroquine-related retinopathy.
Detailed description
Hydroxychloroquine (HCQ) is a widely used drug used to treat disorders of inflammation in the body with up to 320,000 people estimated to be on this drug in the UK alone. Retinopathy due to HCQ is a significant problem, necessitating yearly screening which can only realistically take place in hospital eye units where funding and capacity constraints limit the provision of services.
Electroretinography is a non-invasive method of testing for eye retinal problems, which works by flashing light (in certain patterns and brightness) into eyes and measuring the electrical response through fine wires placed on the eye surface or behind the eyelid, and is considered by many authors to be a gold-standard test to detect HCQ retinopathy. Their use has been limited due to the high expertise required to undertake and interpret tests, limited availability of testing, and high test burden, however newer electroretinography devices have been developed by a company called LKC Technologies, which are faster to perform, use leads placed on the skin (rather than the eye surface) which are more comfortable, easier to use by healthcare technicians, and can be done without the need for dilating eyedrops. The two devices being tested in this study are:
- The RETEval = a handheld electroretinography testing device
- The UTAS multifocal ERG = a trolley-mounted electroretinography testing device
These innovations may make testing far easier to develop in both hospital eye service, and potentially even general settings such as outpatient clinics, general practices, and optometrists. This study aims to evaluate the performance of devices to detect and classify participants in 4 main groups:
- Normative control participants (n=35)
- Patients taking HCQ but without retinopathy (n=35)
- Patients taking HCQ with indeterminate features of retinopathy (also known as POSSIBLE retinopathy) (n=35)
- Patients taking HCQ with definite retinopathy
Device outputs will be analysed and compared with masked graded screening results (incorporating spectral-domain macular optical coherence tomography and autofluorescence as standard, taken on the same visit) to generate device- and device-output-specific sensitivities and specificities. If a signal is found, the feasibility outcomes from this study will inform the study methodology and timelines for a larger trial if necessary.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Normative Controls | – | Diagnostic Test: Hand-Held Full-Field Skin-Electrode Electroretinography (Device to be evaluated), Diagnostic Test: Trolley-Mounted Multifocal Skin-Electrode Electroretinography (Device to be evaluated), Diagnostic Test: Spectral-Domain Optical Coherence Tomography (Standard of Care test), Diagnostic Test: Macular Autofluorescence (Standard of Care test)Age- and sex- matched normal controls |
| On Hydroxychloroquine, NO retinopathy | – | Diagnostic Test: Hand-Held Full-Field Skin-Electrode Electroretinography (Device to be evaluated), Diagnostic Test: Trolley-Mounted Multifocal Skin-Electrode Electroretinography (Device to be evaluated), Diagnostic Test: Spectral-Domain Optical Coherence Tomography (Standard of Care test), Diagnostic Test: Macular Autofluorescence (Standard of Care test)Participants over 18 years on hydroxychloroquine without hydroxychloroquine-related retinopathy |
| On Hydroxychloroquine, POSSIBLE retinopathy | – | Diagnostic Test: Hand-Held Full-Field Skin-Electrode Electroretinography (Device to be evaluated), Diagnostic Test: Trolley-Mounted Multifocal Skin-Electrode Electroretinography (Device to be evaluated), Diagnostic Test: Spectral-Domain Optical Coherence Tomography (Standard of Care test), Diagnostic Test: Macular Autofluorescence (Standard of Care test)Participants over 18 years on hydroxychloroquine with possible (indeterminate) hydroxychloroquine-related retinopathy |
| On Hydroxychloroquine, DEFINITE retinopathy | – | Diagnostic Test: Hand-Held Full-Field Skin-Electrode Electroretinography (Device to be evaluated), Diagnostic Test: Trolley-Mounted Multifocal Skin-Electrode Electroretinography (Device to be evaluated), Diagnostic Test: Spectral-Domain Optical Coherence Tomography (Standard of Care test), Diagnostic Test: Macular Autofluorescence (Standard of Care test)Participants over 18 years on hydroxychloroquine with definite hydroxychloroquine-related retinopathy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Age- and sex-matched control group (n=35) On hydroxychloroquine without retinopathy (n=35) On hydroxychloroquine with possible retinopathy (n=35) On hydroxychloroquine with definite retinopathy (n=35)
Key inclusion criteria (5 listed)
- Age ≥18 years
- HCQ groups:
- Control group:
Key exclusion criteria (21 listed)
- Cataract grade ≥3 of any subtype
- Recent cataract surgery within 4 weeks of recruitment
- Significant media opacity or corneal disease including, but not limited to, corneal oedema, corneal scarring, keratoconus, previous corneal transplants, severe keratoconjunctivitis sicca (requiring the use of topical serum, immunosuppressive or analogous therapy, or procedural treatment).
- Significant macular co-pathology including, but not limited to, macular degeneration, macular scarring, cystic macular oedema (for any reason), staphyloma.
- Inherited retinal and/or macular dystrophies including colour vision deficiencies
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hand-Held Full-Field Skin-Electrode Electroretinography (Device to be evaluated)RETEval Complete hand-held electroretinogram | Diagnostic test | Normative Controls, On Hydroxychloroquine, DEFINITE retinopathy, On Hydroxychloroquine, NO retinopathy, On Hydroxychloroquine, POSSIBLE retinopathy |
| Trolley-Mounted Multifocal Skin-Electrode Electroretinography (Device to be evaluated)UTAS multifocal electroretinogram | Diagnostic test | Normative Controls, On Hydroxychloroquine, DEFINITE retinopathy, On Hydroxychloroquine, NO retinopathy, On Hydroxychloroquine, POSSIBLE retinopathy |
| Spectral-Domain Optical Coherence Tomography (Standard of Care test)Heidelberg Engineering Spectralis Spectral-Domain Optical Coherence Tomography (macular structural scan) | Diagnostic test | Normative Controls, On Hydroxychloroquine, DEFINITE retinopathy, On Hydroxychloroquine, NO retinopathy, On Hydroxychloroquine, POSSIBLE retinopathy |
| Macular Autofluorescence (Standard of Care test)Heidelberg Engineering Spectralis Autofluorescence imaging (macular structural image) | Diagnostic test | Normative Controls, On Hydroxychloroquine, DEFINITE retinopathy, On Hydroxychloroquine, NO retinopathy, On Hydroxychloroquine, POSSIBLE retinopathy |
Primary outcome
The sensitivity and specificity of both devices to discriminate between NO, POSSIBLE and DEFINITE hydroxychloroquine retinopathy compared to standard screening tests
Time frame: All tests required to determine sensitivity and specificity of both devices compared to standard retinal imaging will be completed in a single visit. Safety will be evaluated up to 1 week post-visit.
Primary Outcome
3 secondary outcomes
To compare the sensitivity and specificity of undilated versus dilated testing with the multifocal ERG device, for all categories of hydroxychloroquine retinopathy
Time frame: All tests required to determine this outcome will be completed at a single visit. Safety will be evaluated up to 1 week post-visit.
To determine the patient acceptability of both devices evaluated using standardised, study-specific questionnaires
Time frame: All tests required to determine this outcome will be completed at a single visit. Safety will be evaluated up to 1 week post-visit.
To determine the proportion and recruitment rate of patients in each category of hydroxychloroquine retinopathy who consent to join this study.
Time frame: All tests required to determine this outcome will be completed at a single visit. Safety will be evaluated up to 1 week post-visit.
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 6 Aug 2025.
- Derived from this study: PubMed 39719323Lee CN, Wafa HA, Murphy G, Galloway J, Mahroo OA, Jackson TL. Novel electroretinography devices to detect hydroxychloroquine retinopathy: study protocol for a diagnostic accuracy and feasibility study. BMJ Open Ophthalmol. 2024 Dec 24;9(1):e001898. doi: 10.1136/bmjophth-2024-001898.
- Individual participant dataSharing planned: Undecided
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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.
Professor Timothy L Jackson study chair
King's College Hospital NHS Trust
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 Hydroxychloroquine Retinopathy, run by King's College Hospital NHS Trust at 1 site in United Kingdom.
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 5 inclusion and 21 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 6 Aug 2025. 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 Kingdom. 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 Dr Chan Ning Lee (020 3299 1297, channing.lee2@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The sensitivity and specificity of both devices to discriminate between NO, POSSIBLE and DEFINITE hydroxychloroquine retinopathy compared to standard screening tests (time frame: All tests required to determine sensitivity and specificity of both devices compared to standard retinal imaging will be completed in a single visit. Safety will be evaluated up to 1 week post-visit.). 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 NCT06035887, which also lists 1 linked publication.
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 6 Aug 2025.