Understanding Retinal Function, Vision Loss, and Retinal Toxicity Associated with Hydroxychloroquine Use: A Comprehensive Systematic Literature Review and Exploration of Biomarkers.

Abstract

Objectives: This review-based project will systematically analyse the current body of literature, offering a comprehensive understanding of hydroxychloroquine (HCQ) retinopathy. By understanding the correlation between HCQ usage and the mechanism of vision loss, we aim to explore the clinical biomarkers of hydroxychloroquine retinopathy (HCQR) and how sensitive different screening devices are to detecting these biomarkers. Furthermore, our exploration of biomarkers indicative of retinal damage will contribute to enhancing the safety and monitoring of patients undergoing HCQ therapy. Study Design: The search was done using Google Scholar, Scopus, PubMed, Medline, the Web of Science, the Cochrane Library, and the Joanna Briggs Institute (JBI). Several of the 6,659 studies were found. After removing the duplicates, 1.772 studies remained. The title, abstract, or sometimes the whole paper of the remaining studies were evaluated based on the inclusion or exclusion criteria of this review. Only 46 studies met the criteria. Two reviewers used an extraction tool based on the JBI critical appraisal tool; cohort studies and quasi-experimental studies were used to critically appraise the papers (Appendix 2). As a result, 24 papers were selected for data extraction. Results: Due to the generally low quality of evidence, meta-analysis was considered unsuitable. Therefore, the findings were summarized using narrative synthesis with supporting tables. Data was collected using a data extraction instrument based on the principles of effective practice and organisation of care (EPOC) (Glenton et al. 2022). The review suggests that a daily dose > 5 mg/kg/day poses the highest risk for HCQR, with common early signs being retinal thinning. However, it is noteworthy that many studies couldn't fully explain HCQR's mechanism (Greenstein et al. 2015; Marmor et al. 2016; Garrity et al. 2019; Godinho et al. 2020). This review revealed that SD-OCT and mfERG demonstrated the highest sensitivity in detecting early functional and structural changes caused by HCQ, with one possibly occurring before the other (Chen et al. 2010; Greenstein et al. 2015; Yusuf et al. 2021; Melles and Marmor 2022)