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      Hydroxychloroquine-induced Retinal Toxicity

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          Abstract

          Long-term use of hydroxychloroquine can cause retinopathy, which may result in severe and progressive visual loss. In the past decade, hydroxychloroquine use has markedly increased and modern retinal imaging techniques have enabled the detection of early, pre-symptomatic disease. As a consequence, the prevalence of retinal toxicity in long-term hydroxychloroquine users is known to be higher than was previously estimated. The pathophysiology of the retinopathy is incompletely characterised, although significant advances have been made in understanding the disease from clinical imaging studies. Hydroxychloroquine retinopathy elicits sufficient public health concern to justify the implementation of retinopathy screening programs for patients at risk. Here, we describe the historical background of hydroxychloroquine retinopathy and summarize its current understanding. We review the utility and limitations of each of the mainstream diagnostic tests used to detect hydroxychloroquine retinopathy. The key considerations towards a consensus on the definition of hydroxychloroquine retinopathy are outlined in the context of what is known of the natural history of the disease. We compare the current screening recommendations for hydroxychloroquine retinopathy, identifying where additional evidence is required, and the management of proven cases of toxicity. Finally, we highlight the areas for further investigation, which may further reduce the risk of visual loss in hydroxychloroquine users.

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          Most cited references183

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          2019 update of the EULAR recommendations for the management of systemic lupus erythematosus

          Our objective was to update the EULAR recommendations for the management of systemic lupus erythematosus (SLE), based on emerging new evidence. We performed a systematic literature review (01/2007–12/2017), followed by modified Delphi method, to form questions, elicit expert opinions and reach consensus. Treatment in SLE aims at remission or low disease activity and prevention of flares. Hydroxychloroquine is recommended in all patients with lupus, at a dose not exceeding 5 mg/kg real body weight. During chronic maintenance treatment, glucocorticoids (GC) should be minimised to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn. Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of GC. In persistently active or flaring extrarenal disease, add-on belimumab should be considered; rituximab (RTX) may be considered in organ-threatening, refractory disease. Updated specific recommendations are also provided for cutaneous, neuropsychiatric, haematological and renal disease. Patients with SLE should be assessed for their antiphospholipid antibody status, infectious and cardiovascular diseases risk profile and preventative strategies be tailored accordingly. The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion.
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            Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology

            Despite widespread clinical use of antimalarial drugs such as hydroxychloroquine and chloroquine in the treatment of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and other inflammatory rheumatic diseases, insights into the mechanism of action of these drugs are still emerging. Hydroxychloroquine and chloroquine are weak bases and have a characteristic 'deep' volume of distribution and a half-life of around 50 days. These drugs interfere with lysosomal activity and autophagy, interact with membrane stability and alter signalling pathways and transcriptional activity, which can result in inhibition of cytokine production and modulation of certain co-stimulatory molecules. These modes of action, together with the drug's chemical properties, might explain the clinical efficacy and well-known adverse effects (such as retinopathy) of these drugs. The unknown dose-response relationships of these drugs and the lack of definitions of the minimum dose needed for clinical efficacy and what doses are toxic pose challenges to clinical practice. Further challenges include patient non-adherence and possible context-dependent variations in blood drug levels. Available mechanistic data give insights into the immunomodulatory potency of hydroxychloroquine and provide the rationale to search for more potent and/or selective inhibitors.
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              Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision).

              The American Academy of Ophthalmology recommendations on screening for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy are revised in light of new information about the prevalence of toxicity, risk factors, fundus distribution, and effectiveness of screening tools.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                30 May 2023
                2023
                : 14
                : 1196783
                Affiliations
                [1] 1 Oxford Eye Hospital and Nuffield Department of Clinical Neurosciences , John Radcliffe Hospital , University of Oxford , Oxford, United Kingdom
                [2] 2 Department of Ophthalmology , Hanyang University Hospital , Hanyang University College of Medicine , Seoul, South Korea
                Author notes

                Edited by: Ik-Hyun Cho, Kyung Hee University, South Korea

                Reviewed by: Flavia Chiosi, Colli Monaldi Hospital, Italy

                Heather Mack, Eye Surgery Associates, Australia

                *Correspondence: Seong Joon Ahn, ahnsj81@ 123456gmail.com
                Article
                1196783
                10.3389/fphar.2023.1196783
                10267834
                37324471
                42f348f1-b4dc-4874-8028-998670ba9e8b
                Copyright © 2023 Yusuf, Charbel Issa and Ahn.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 March 2023
                : 17 May 2023
                Funding
                This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government MSIT (NRF-2021R1G1A1013360); the National Institute for Health Research (NIHR) Biomedical Research Centre, Oxford, UK; the Medical Research Council UK (MR/R000735/1). Knoop Junior Research Fellowship, St. Cross College, Oxford.
                Categories
                Pharmacology
                Review
                Custom metadata
                Neuropharmacology

                Pharmacology & Pharmaceutical medicine
                hydroxychloroquine,optical coherence tomography,retinal imaging,screening,toxicity,retinopathy,hydroxychloroquine retinopathy

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