Monitoring for retinal toxicity in patients taking hydroxychloroquine and chloroquine

Monitoring for retinal toxicity in patients taking hydroxychloroquine and chloroquine The British Society for Rheumatology (BSR) has published updated guidelines on the prescribing and monitoring of DMARDs, which include recommendations for more intensive screening for retinal toxicity in patients on antimalarials [1]. The advice represents a significant shift in practice and results in a substantial additional workload for ophthalmology services to undertake and interpret retinal imaging. In follow up to the BSR guidelines, and in response to the recognition of the increasing number of patients identified with advanced HCQ retinopathy [2, 3], the Royal College of Ophthalmologists (RCOphth) have now published their own, more detailed, recommendations; these provide additional clarity to the BSR guidelines regarding the diagnostic tests required and suggested monitoring schedules [4]. The current BSR guidelines state ‘Patients should have baseline formal ophthalmic examination, ideally including objective retinal assessment for example using optical coherence tomography, within 1 year of commencing an antimalarial drug’ [1]. During treatment, it recommends ‘annual eye assessment (ideally including optical coherence tomography) if treatment is continued for >5 years’ [1]. The RCOphth expands upon these recommendations, highlighting who should be screened, where screening should take place, what screening tests to use both at baseline and at screening visits, how to interpret results of screening and how to manage toxicity [4]. The RCOphth guidelines specify the diagnostic tests for screening: 10-2 Humphrey visual field testing (using a white stimulus), followed by pupillary dilation and imaging with both spectral domain optical coherence tomography and widefield fundus autofluorescence. Screening should take place in the hospital eye service under the supervision of an ophthalmologist. The role of screening is to detect the earliest evidence of definite HCQ retinopathy, with a recommendation made to the prescribing physician to consider alternative treatment options if retinopathy is detected [4]. Baseline screening does not need to delay therapy, but should ideally take place within the first 6 months, and certainly within the first year, of starting HCQ therapy. It is the responsibility of the prescribing physician to refer to ophthalmology for enrolment in screening. Subsequent screening frequency then depends upon individual risk of toxicity. Most patients need to begin screening after they have been on therapy for 5 years, at which point annual screening should commence. Patients at increased risk of toxicity should commence annual screening from the outset. Such additional risk factors include: use of chloroquine (rather than HCQ), concomitant tamoxifen use, impaired renal function (estimated glomerular filtration rate of <50 ml/min/1.73 m2) and doses of HCQ greater than 5 mg per kilogram per day (absolute body weight, rather than ideal body weight). The decision to institute earlier screening should be based upon the recommendation of the ophthalmologist. It is therefore important to communicate known risk factors for HCQ retinopathy to ophthalmology for the purposes of screening. A referral template is attached to the RCOphth guidelines on screening for HCQ retinopathy [4]. Screening results will be reported as either no toxicity, possible toxicity (e.g. an abnormal spectral domain optical coherence tomography result, but normal Humphrey visual field testing) or definite toxicity (ideally with one subjective and one objective test demonstrating features consistent with HCQ retinopathy). The guidelines provide detailed advice on additional tests for patients with possible toxicity, including referral for other tests such as multifocal electroretinography in specific patient groups. In cases of definite toxicity, the guidelines recommend that the responsibility for stopping treatment should be with the treating physician, explicitly stating that it would not be appropriate for ophthalmologists to stop anti-malarial treatment [4]. Helpfully, the recommendations address the organization of services. They highlight that written communication from the ophthalmologist indicating the outcome of each screening episode be sent to the patient, prescribing physician and general practitioner. In the event of failure to attend screening, patients should not be automatically discharged. Patients should be reminded of the purpose of screening and the approximate interval to the next screening appointment stated. A patient information leaflet has been produced by the Macular Society with input from the RCOphth guideline development group [5]. In recognition of the workload, the guidelines advise that ophthalmologists who regularly interpret HCQ retinopathy screening test results should have sessional commitments allocated within their work plan [4]. The revised guidelines from the RCOphth are a welcome support to the existing BSR DMARD guidelines [1, 4]. The recommendations are clear, and the rheumatology community now needs to work with ophthalmology services to ensure that appropriate screening is put in place. Future research is needed to understand the risks, benefits and economics of antimalarial therapy in rheumatic disease. Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this manuscript. Disclosure statement: The authors have declared no conflicts of interest. References 1 Ledingham J, Gullick N, Irving K et al.   BSR and BHPR guideline for the prescription and monitoring of non-biologic disease-modifying anti-rheumatic drugs. Rheumatology (Oxford)  2017; 56: 2257. Google Scholar CrossRef Search ADS PubMed  2 Latasiewicz M, Gourier H, Yusuf IH et al.   Hydroxychloroquine retinopathy: an emerging problem. Eye  2017; 31: 972– 6. Google Scholar CrossRef Search ADS PubMed  3 Yusuf IH, Sharma S, Luqmani R, Downes SM. Hydroxychloroquine retinopathy. Eye  2017; 31: 828– 45. Google Scholar CrossRef Search ADS PubMed  4 Royal College of Ophthalmologists (RCOphth). Hydroxychloroquine and chloroquine retinopathy: recommendations on screening – membership consultation. 2018. https://www.rcophth.ac.uk/standards-publications-research/clinical-guidelines/. 5 Macular Society. Eye screening for patients taking hydroxychloroquine (Plaquenil®). Macular Society. 2018. https://www.macularsociety.org/resource/hydroxychloroquine-retinopathy. © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Rheumatology Oxford University Press

Monitoring for retinal toxicity in patients taking hydroxychloroquine and chloroquine

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Oxford University Press
Copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com
ISSN
1462-0324
eISSN
1462-0332
D.O.I.
10.1093/rheumatology/key024
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Abstract

The British Society for Rheumatology (BSR) has published updated guidelines on the prescribing and monitoring of DMARDs, which include recommendations for more intensive screening for retinal toxicity in patients on antimalarials [1]. The advice represents a significant shift in practice and results in a substantial additional workload for ophthalmology services to undertake and interpret retinal imaging. In follow up to the BSR guidelines, and in response to the recognition of the increasing number of patients identified with advanced HCQ retinopathy [2, 3], the Royal College of Ophthalmologists (RCOphth) have now published their own, more detailed, recommendations; these provide additional clarity to the BSR guidelines regarding the diagnostic tests required and suggested monitoring schedules [4]. The current BSR guidelines state ‘Patients should have baseline formal ophthalmic examination, ideally including objective retinal assessment for example using optical coherence tomography, within 1 year of commencing an antimalarial drug’ [1]. During treatment, it recommends ‘annual eye assessment (ideally including optical coherence tomography) if treatment is continued for >5 years’ [1]. The RCOphth expands upon these recommendations, highlighting who should be screened, where screening should take place, what screening tests to use both at baseline and at screening visits, how to interpret results of screening and how to manage toxicity [4]. The RCOphth guidelines specify the diagnostic tests for screening: 10-2 Humphrey visual field testing (using a white stimulus), followed by pupillary dilation and imaging with both spectral domain optical coherence tomography and widefield fundus autofluorescence. Screening should take place in the hospital eye service under the supervision of an ophthalmologist. The role of screening is to detect the earliest evidence of definite HCQ retinopathy, with a recommendation made to the prescribing physician to consider alternative treatment options if retinopathy is detected [4]. Baseline screening does not need to delay therapy, but should ideally take place within the first 6 months, and certainly within the first year, of starting HCQ therapy. It is the responsibility of the prescribing physician to refer to ophthalmology for enrolment in screening. Subsequent screening frequency then depends upon individual risk of toxicity. Most patients need to begin screening after they have been on therapy for 5 years, at which point annual screening should commence. Patients at increased risk of toxicity should commence annual screening from the outset. Such additional risk factors include: use of chloroquine (rather than HCQ), concomitant tamoxifen use, impaired renal function (estimated glomerular filtration rate of <50 ml/min/1.73 m2) and doses of HCQ greater than 5 mg per kilogram per day (absolute body weight, rather than ideal body weight). The decision to institute earlier screening should be based upon the recommendation of the ophthalmologist. It is therefore important to communicate known risk factors for HCQ retinopathy to ophthalmology for the purposes of screening. A referral template is attached to the RCOphth guidelines on screening for HCQ retinopathy [4]. Screening results will be reported as either no toxicity, possible toxicity (e.g. an abnormal spectral domain optical coherence tomography result, but normal Humphrey visual field testing) or definite toxicity (ideally with one subjective and one objective test demonstrating features consistent with HCQ retinopathy). The guidelines provide detailed advice on additional tests for patients with possible toxicity, including referral for other tests such as multifocal electroretinography in specific patient groups. In cases of definite toxicity, the guidelines recommend that the responsibility for stopping treatment should be with the treating physician, explicitly stating that it would not be appropriate for ophthalmologists to stop anti-malarial treatment [4]. Helpfully, the recommendations address the organization of services. They highlight that written communication from the ophthalmologist indicating the outcome of each screening episode be sent to the patient, prescribing physician and general practitioner. In the event of failure to attend screening, patients should not be automatically discharged. Patients should be reminded of the purpose of screening and the approximate interval to the next screening appointment stated. A patient information leaflet has been produced by the Macular Society with input from the RCOphth guideline development group [5]. In recognition of the workload, the guidelines advise that ophthalmologists who regularly interpret HCQ retinopathy screening test results should have sessional commitments allocated within their work plan [4]. The revised guidelines from the RCOphth are a welcome support to the existing BSR DMARD guidelines [1, 4]. The recommendations are clear, and the rheumatology community now needs to work with ophthalmology services to ensure that appropriate screening is put in place. Future research is needed to understand the risks, benefits and economics of antimalarial therapy in rheumatic disease. Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this manuscript. Disclosure statement: The authors have declared no conflicts of interest. References 1 Ledingham J, Gullick N, Irving K et al.   BSR and BHPR guideline for the prescription and monitoring of non-biologic disease-modifying anti-rheumatic drugs. Rheumatology (Oxford)  2017; 56: 2257. Google Scholar CrossRef Search ADS PubMed  2 Latasiewicz M, Gourier H, Yusuf IH et al.   Hydroxychloroquine retinopathy: an emerging problem. Eye  2017; 31: 972– 6. Google Scholar CrossRef Search ADS PubMed  3 Yusuf IH, Sharma S, Luqmani R, Downes SM. Hydroxychloroquine retinopathy. Eye  2017; 31: 828– 45. Google Scholar CrossRef Search ADS PubMed  4 Royal College of Ophthalmologists (RCOphth). Hydroxychloroquine and chloroquine retinopathy: recommendations on screening – membership consultation. 2018. https://www.rcophth.ac.uk/standards-publications-research/clinical-guidelines/. 5 Macular Society. Eye screening for patients taking hydroxychloroquine (Plaquenil®). Macular Society. 2018. https://www.macularsociety.org/resource/hydroxychloroquine-retinopathy. © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Journal

RheumatologyOxford University Press

Published: Feb 26, 2018

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