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      Quantitative Fundus Autofluorescence in Systemic Chloroquine/Hydroxychloroquine Therapy

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          Abstract

          Purpose

          To investigate the effect of systemic chloroquine/hydroxychloroquine (CQ/HCQ) on outer retinal health using quantitative fundus autofluorescence (QAF) imaging.

          Methods

          For this prospective, cross-sectional study, 44 CQ/HCQ patients and 25 age-matched controls underwent multimodal retinal imaging including QAF (488 nm) and spectral-domain optical coherence tomography (SD-OCT) in addition to the recommended CQ/HCQ screening procedures. Custom written FIJI plugins enabled detailed QAF analysis and correlation with retinal thickness and comparison to the healthy controls.

          Results

          Out of 44 patients, 29 (mean age 43.5 ± 12.2, range 22–59 years) exposed to CQ/HCQ (mean cumulative dose 724.2 ± 610.4 g, median 608.0 g, range 18.6–2171.0 g) met eligibility criteria. Four of these 29 patients had bull's-eye maculopathy (BEM). Mean QAF values were significantly higher in CQ/HCQ patients than in healthy controls. QAF increase started early after treatment onset, remained high even years after treatment cessation, and was not accompanied by pathologies in the other screening methods, including retinal thicknesses (except in BEM patients).

          Conclusions

          QAF might be a useful tool in retinal imaging and in verifying systemic CQ/HCQ intake. The early onset and preserved high levels of QAF parallel findings of CQ deposition in the retina in animal models. Whether QAF can be used as a screening tool to detect early CQ/HCQ related maculopathy is the subject of long-term ongoing studies.

          Translation Relevance

          Experimental QAF imaging in systemic CQ/HCQ therapy monitoring might be a useful tool to indicate the drug or its metabolites and to detect metabolic retinal changes.

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          Most cited references60

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          Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies

          The coronavirus disease 2019 (COVID-19) virus is spreading rapidly, and scientists are endeavoring to discover drugs for its efficacious treatment in China. Chloroquine phosphate, an old drug for treatment of malaria, is shown to have apparent efficacy and acceptable safety against COVID-19 associated pneumonia in multicenter clinical trials conducted in China. The drug is recommended to be included in the next version of the Guidelines for the Prevention, Diagnosis, and Treatment of Pneumonia Caused by COVID-19 issued by the National Health Commission of the People's Republic of China for treatment of COVID-19 infection in larger populations in the future.
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            A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19

            Purpose COVID-19 (coronavirus disease 2019) is a public health emergency of international concern. As of this time, there is no known effective pharmaceutical treatment, although it is much needed for patient contracting the severe form of the disease. The aim of this systematic review was to summarize the evidence regarding chloroquine for the treatment of COVID-19. Methods PubMed, EMBASE, and three trial Registries were searched for studies on the use of chloroquine in patients with COVID-19. Results We included six articles (one narrative letter, one in-vitro study, one editorial, expert consensus paper, two national guideline documents) and 23 ongoing clinical trials in China. Chloroquine seems to be effective in limiting the replication of SARS-CoV-2 (virus causing COVID-19) in vitro. Conclusions There is rationale, pre-clinical evidence of effectiveness and evidence of safety from long-time clinical use for other indications to justify clinical research on chloroquine in patients with COVID-19. However, clinical use should either adhere to the Monitored Emergency Use of Unregistered Interventions (MEURI) framework or be ethically approved as a trial as stated by the World Health Organization. Safety data and data from high-quality clinical trials are urgently needed.
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              The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.

              Hydroxychloroquine sulfate is widely used for the long-term treatment of autoimmune conditions but can cause irreversible toxic retinopathy. Prior estimations of risk were low but were based largely on short-term users or severe retinal toxicity (bull's eye maculopathy). The risk may be much higher because retinopathy can be detected earlier when using more sensitive screening techniques.
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                Author and article information

                Journal
                Transl Vis Sci Technol
                Transl Vis Sci Technol
                tvst
                TVST
                Translational Vision Science & Technology
                The Association for Research in Vision and Ophthalmology
                2164-2591
                28 August 2020
                August 2020
                : 9
                : 9
                : 42
                Affiliations
                [1 ]University Hospital Würzburg, Department of Ophthalmology, Würzburg, Germany
                [2 ]University of Alabama at Birmingham, Department of Ophthalmology, Birmingham, AL, USA
                [3 ]University Hospital Bonn, Department of Ophthalmology, Bonn, Germany
                Author notes
                Correspondence: Thomas Ach, MD, FEBO. University Hospital Bonn, Department of Ophthalmology, Ernst Abbe Strasse 2, Bonn, 53127, Germany. e-mail: thomas.ach@ 123456ukbonn.de
                [*]

                CR and AB contributed equally to this work and should be considered co-first authors.

                Article
                TVST-20-2534
                10.1167/tvst.9.9.42
                7463177
                4017e3ad-4c2a-4459-b1b4-25b70a5ccd94
                Copyright 2020 The Authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 03 August 2020
                : 23 April 2020
                Page count
                Pages: 15
                Categories
                Article
                Article

                quantitative fundus autofluorescence,chloroquine,hydroxychloroquine,bulls eye maculopathy

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