Novel electroretinography devices to detect hydroxychloroquine retinopathy: study protocol for a diagnostic accuracy and feasibility study

Abstract

Introduction: Annual screening for hydroxychloroquine (HCQ) retinopathy is recommended, and electroretinography (ERG) is considered a gold-standard test, but there are screening shortfalls and standard ERG is burdensome and has limited availability. Newer, portable ERG devices using skin-based electrodes may increase screening capacity but need validation. This study aims to determine initial device accuracies and feasibility of further research.

Methods and analysis: Prospective diagnostic device accuracy and feasibility study comparing novel ERG devices to standard screening tests. Three groups of 35 participants on HCQ, categorised by HCQ retinopathy (definite, possible and no retinopathy), and 35 healthy control participants, recruited by consecutive sampling, will have full field and multifocal ERG index tests, delivered using skin-contact electrodes by two devices-RETEval full-field and UTAS multifocal ERG, both manufactured by LKC Technologies (Gaithersburg, Maryland, USA), compared with spectral-domain optical coherence tomography and autofluorescence reference tests graded by two masked, independent retinal specialists. Eligible HCQ participants will either have diagnosed HCQ retinopathy or be eligible for screening per UK guidelines. Healthy control participants will have no prior HCQ exposure and be of similar age and sex to HCQ participants. Primary outcome is device-specific sensitivity and specificity. Secondary outcomes include the effect of dilation on device outputs, analysis of discriminatory waveforms, device acceptability and recruitment rate. Safety outcomes include adverse and serious adverse events and device events.

Ethics and dissemination: Cambridge East ethics committee gave a favourable opinion (24/EE/0011, 23/02/2024). Results will be published in a peer-reviewed ophthalmology journal.

Trial registration number: ClinicalTrials.gov NCT06035887.

Keywords: Clinical Trial; Diagnostic tests/Investigation; Electrophysiology; Retina.

Figure 1. Current recommended flow diagram for screening of patients on HCQ or CQ. Reproduced from the RCOphth HCQ and CQ screening guidelines. Abbreviations: CQ, chloroquine; eGFR, estimated glomerular filtration rate; FAF, fundus autofluorescence; HCQ, hydroxychloroquine; HVF, Humphrey automated visual field; mfERG, multifocal electroretinography; SD-OCT, spectral-domain optical coherence tomography.

Figure 2. Study participant flow diagram. Abbreviations: ERG, electroretinography; FAF, fundus autofluorescence; HCQ, hydroxychloroquine; mfERG, multifocal electroretinography; OCT, optical coherence tomography.