Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision)
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Background 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.Pattern of retinopathy Although the locus of toxic damage is parafoveal in many eyes, Asian patients often show an extramacular pattern of damage. DOSE: We recommend a maximum daily HCQ use of ≤5.0 mg/kg real weight, which correlates better with risk than ideal weight. There are no similar demographic data for CQ, but dose comparisons in older literature suggest using ≤2.3 mg/kg real weight.Risk of toxicity The risk of toxicity is dependent on daily dose and duration of use. At recommended doses, the risk of toxicity up to 5 years is under 1% and up to 10 years is under 2%, but it rises to almost 20% after 20 years. However, even after 20 years, a patient without toxicity has only a 4% risk of converting in the subsequent year.Major risk factors High dose and long duration of use are the most significant risks. Other major factors are concomitant renal disease, or use of tamoxifen.Screening schedule A baseline fundus examination should be performed to rule out preexisting maculopathy. Begin annual screening after 5 years for patients on acceptable doses and without major risk factors.Screening tests The primary screening tests are automated visual fields plus spectral-domain optical coherence tomography (SD OCT). These should look beyond the central macula in Asian patients. The multifocal electroretinogram (mfERG) can provide objective corroboration for visual fields, and fundus autofluorescence (FAF) can show damage topographically. Modern screening should detect retinopathy before it is visible in the fundus.Toxicity Retinopathy is not reversible, and there is no present therapy. Recognition at an early stage (before any RPE loss) is important to prevent central visual loss. However, questionable test results should be repeated or validated with additional procedures to avoid unnecessary cessation of valuable medication.Counseling Patients (and prescribing physicians) should be informed about risk of toxicity, proper dose levels, and the importance of regular annual screening.
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Revised American Academy of Ophthalmology guidance limits hydroxychloroquine dosing to less than 5 mg/kg absolute body weight, based on the Kaiser-Permanente study.
“The retrospective Kaiser-Permanente study was the basis for the revised American Academy of Ophthalmology (AAO) guidance to limit hydroxychloroquine dosing to less than 5 mg/kg absolute body weight (26).”
From Association of Higher Hydroxychloroquine Blood Levels With Reduced Thrombosis Risk in Systemic Lupus Erythematosus (2021) · cites this paper as [26]
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“The new recommendations advise use of HCQ at <5 mg/kg actual body weight to reduce the risk of future retinopathy (26).”
BackgroundRisk of retinal toxicity in longterm users of hydroxychloroquine
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- Authors
- Marmor, M. F., Kellner, U., Lai, T. Y. Y., Melles, R. B., & Mieler, W. F.
- Affiliations
- Stanford Medicine (US)
- Helios Hospital Siegburg (DE)
- Chinese University of Hong Kong (HK)
- Kaiser Permanente Redwood City Medical Center (US)
- University of Illinois Chicago (US)
- Venue
- Ophthalmology
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 123
- Issue
- 6
- Pages
- 1386-1394
- ISSN
- 0161-6420 (ISSN-L)
- OpenAlex
- W2302013022
- Cited by
- 1,164
- References
- 32
- Citations by year
- 2026: 73 · 2025: 89 · 2024: 96 · 2023: 83 · 2022: 113 · 2021: 174 · 2020: 245 · 2019: 100 · 2018: 86 · 2017: 78 · 2016: 23 · 2015: 1 · 2014: 2 · 2013: 1
- FWCI
- 101.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Drug-Induced Ocular Toxicity
- Health Sciences › Medicine › Ophthalmology › Ocular and Laser Science Research
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- chloroquine retinopathy, hydroxychloroquine retinopathy, retinal toxicity, retinopathy screening, screening guidelines, risk factors, spectral-domain optical coherence tomography, multifocal electroretinogram, fundus autofluorescence, tamoxifen, kidney disease, patient counseling
- MeSH terms
- Academies and Institutes, Adult, Chloroquine, Electroretinography, Female, Fluorescein Angiography, Humans, Hydroxychloroquine, Maximum Allowable Concentration, Middle Aged, Ophthalmology, Retinal Diseases, Risk Factors, United States, Vision Disorders, Visual Acuity, Visual Fields, Antirheumatic Agents, Tomography, Optical Coherence, Asian People, Visual Field Tests
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