Novel ERG for Detection of Hydroxychloroquine Retinopathy

Sponsor

King's College Hospital NHS Trust (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06035887

Collaborator

LUPUS UK (Other), King's College Hospital Charity (Other)

140

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief 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 participants characterised by presence or absence of hydroxychloroquine-related retinopathy.

Condition or Disease	Intervention/Treatment	Phase
Hydroxychloroquine 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)

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

Study Type:

Observational

Anticipated Enrollment :

140 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

A Feasibility Study Using Novel, Portable Electroretinography Devices to Detect Hydroxychloroquine Retinopathy

Anticipated Study Start Date :

Dec 1, 2023

Anticipated Primary Completion Date :

Nov 1, 2025

Anticipated Study Completion Date :

Nov 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Normative Controls Age- and sex- matched normal controls	Diagnostic Test: Hand-Held Full-Field Skin-Electrode Electroretinography (Device to be evaluated) RETEval Complete hand-held electroretinogram Diagnostic Test: Trolley-Mounted Multifocal Skin-Electrode Electroretinography (Device to be evaluated) UTAS multifocal electroretinogram Diagnostic Test: Spectral-Domain Optical Coherence Tomography (Standard of Care test) Heidelberg Engineering Spectralis Spectral-Domain Optical Coherence Tomography (macular structural scan) Diagnostic Test: Macular Autofluorescence (Standard of Care test) Heidelberg Engineering Spectralis Autofluorescence imaging (macular structural image)
On Hydroxychloroquine, NO retinopathy Participants over 18 years on hydroxychloroquine without hydroxychloroquine-related retinopathy	Diagnostic Test: Hand-Held Full-Field Skin-Electrode Electroretinography (Device to be evaluated) RETEval Complete hand-held electroretinogram Diagnostic Test: Trolley-Mounted Multifocal Skin-Electrode Electroretinography (Device to be evaluated) UTAS multifocal electroretinogram Diagnostic Test: Spectral-Domain Optical Coherence Tomography (Standard of Care test) Heidelberg Engineering Spectralis Spectral-Domain Optical Coherence Tomography (macular structural scan) Diagnostic Test: Macular Autofluorescence (Standard of Care test) Heidelberg Engineering Spectralis Autofluorescence imaging (macular structural image)
On Hydroxychloroquine, POSSIBLE retinopathy Participants over 18 years on hydroxychloroquine with possible (indeterminate) hydroxychloroquine-related retinopathy	Diagnostic Test: Hand-Held Full-Field Skin-Electrode Electroretinography (Device to be evaluated) RETEval Complete hand-held electroretinogram Diagnostic Test: Trolley-Mounted Multifocal Skin-Electrode Electroretinography (Device to be evaluated) UTAS multifocal electroretinogram Diagnostic Test: Spectral-Domain Optical Coherence Tomography (Standard of Care test) Heidelberg Engineering Spectralis Spectral-Domain Optical Coherence Tomography (macular structural scan) Diagnostic Test: Macular Autofluorescence (Standard of Care test) Heidelberg Engineering Spectralis Autofluorescence imaging (macular structural image)
On Hydroxychloroquine, DEFINITE retinopathy Participants over 18 years on hydroxychloroquine with definite hydroxychloroquine-related retinopathy	Diagnostic Test: Hand-Held Full-Field Skin-Electrode Electroretinography (Device to be evaluated) RETEval Complete hand-held electroretinogram Diagnostic Test: Trolley-Mounted Multifocal Skin-Electrode Electroretinography (Device to be evaluated) UTAS multifocal electroretinogram Diagnostic Test: Spectral-Domain Optical Coherence Tomography (Standard of Care test) Heidelberg Engineering Spectralis Spectral-Domain Optical Coherence Tomography (macular structural scan) Diagnostic Test: Macular Autofluorescence (Standard of Care test) Heidelberg Engineering Spectralis Autofluorescence imaging (macular structural image)

Outcome Measures

Primary Outcome Measures

The sensitivity and specificity of both devices to discriminate between NO, POSSIBLE and DEFINITE hydroxychloroquine retinopathy compared to standard screening tests [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

Secondary Outcome Measures

To compare the sensitivity and specificity of undilated versus dilated testing with the multifocal ERG device, for all categories of hydroxychloroquine retinopathy [All tests required to determine this outcome will be completed at a single visit. Safety will be evaluated up to 1 week post-visit.]
Secondary Outcome
To determine the patient acceptability of both devices evaluated using standardised, study-specific questionnaires [All tests required to determine this outcome will be completed at a single visit. Safety will be evaluated up to 1 week post-visit.]
Feasibility Outcome
To determine the proportion and recruitment rate of patients in each category of hydroxychloroquine retinopathy who consent to join this study. [All tests required to determine this outcome will be completed at a single visit. Safety will be evaluated up to 1 week post-visit.]
Feasibility Outcome

Other Outcome Measures

To determine which ERG waveform features (such as implicit time or amplitude) from both devices best discriminate participants with NO hydroxychloroquine retinopathy from those with POSSIBLE and DEFINITE hydroxychloroquine retinopathy [All tests required to determine this outcome will be completed at a single visit. Safety will be evaluated up to 1 week post-visit.]
Exploratory Outcome
To determine if both device waveforms correlate with standard mfERG waveforms in patients receiving hydroxychloroquine [All tests required to determine this outcome will be completed at a single visit. Novel device ERG waveforms will be compared with standard mfERG where undertaken in the preceding 12 months. Safety will be evaluated up to 1 week post-visit.]
Exploratory Outcome

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Inclusion Criteria:

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

Exclusion Criteria:

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
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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

King's College Hospital NHS Trust
LUPUS UK
King's College Hospital Charity

Investigators

Study Chair: Professor Timothy L Jackson, King's College Hospital NHS Trust

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

King's College Hospital NHS Trust

ClinicalTrials.gov Identifier:

NCT06035887

Other Study ID Numbers:

IRAS 317611

First Posted:

Sep 13, 2023

Last Update Posted:

Sep 13, 2023

Last Verified:

Sep 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Yes

Product Manufactured in and Exported from the U.S.:

Keywords provided by King's College Hospital NHS Trust

Electroretinography

Diagnostic Evaluation

Additional relevant MeSH terms:

Retinal Diseases

Study Results

No Results Posted as of Sep 13, 2023