Elsevier

Ophthalmology

Volume 123, Issue 6, June 2016, Pages 1386-1394
Ophthalmology

American Academy of Ophthalmology Statement
Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision)

https://doi.org/10.1016/j.ophtha.2016.01.058Get rights and content

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.

Section snippets

Hydroxychloroquine and Chloroquine Toxicity

The mechanism of CQ and HCQ toxicity is not well understood. High experimental doses have acute effects on the metabolism of retinal cells, but it is not clear how these short-term metabolic effects relate to the slow and chronic damage that characterizes the clinical state of toxicity. Binding to melanin in the RPE may serve to concentrate the agents and contribute to, or prolong, their toxic effects. However, melanin binding also could serve as a mechanism for removing toxic agents from

Statistical Risk of Toxicity

Earlier literature on the prevalence of CQ or HCQ retinopathy included few patients on long-term therapy and only recognized severe toxicity (bull's-eye changes). These reports have been superseded now by a large study of 2361 patients who used HCQ for more than 5 years and were evaluated with 10-2 visual fields or spectral-domain optical coherence tomography (SD OCT) so that toxicity could be recognized before there were any visible signs on fundus examination.2 The overall prevalence of

Dosage Recommendations

On the basis of the risk data described, we recommend that all patients using HCQ keep daily dosage <5.0 mg/kg real weight.2 There may be rare instances when higher doses are needed to manage life-threatening disease or a lower limit is advisable because of major risk factors (described later). Following this guideline will minimize the risk of retinopathy and allow long-term use of HCQ for most patients. Previous recommendations to use ideal body weight for the calculation of dose were based

Major Factors

The most important risk factors are listed in Table 1.

Rationale for Screening

Hydroxychloroquine and CQ retinopathy are not reversible, and cellular damage may progress even after the drugs are stopped. When retinopathy is not recognized until a bull's-eye appears, the disease can progress for years, often with foveal thinning and an eventual loss of visual acuity. However, when retinopathy is recognized early, before RPE damage, there is only mild and limited progression after discontinuing the medication, and the fovea is not threatened.5 Thus, screening may not

Clinical Examination Techniques

Screening techniques that are recommended or that should be avoided are listed in Table 3.

Management of Eyes at Risk or with Retinopathy

No diet or medical therapy has proven effective as yet to prevent, treat, or reduce risk from HCQ or CQ retinopathy other than cessation of the drug. Even stoppage of the drug does not prevent progression of retinopathy, although this is typically mild if the toxicity is recognized before there is RPE damage. Patients with age-related maculopathy or macular dystrophies sometimes are advised to avoid excessive sun exposure and maintain intake of lutein and zeaxanthin (which are foveal

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    Correspondence: Flora Lum, MD, Department of Quality of Care and Knowledge Base Development, American Academy of Ophthalmology, 655 Beach Street, San Francisco, CA 94109-1336. E-mail: [email protected].

    Financial Disclosure(s): The author(s) have made the following disclosure(s): T.Y.Y.L.: Consultant − Allergan, Bayer Healthcare, Novartis Pharmaceuticals, Genentech; Grants/grants pending − Bayer Healthcare, Novartis Pharmaceuticals; Lecture fees − Allergan, Bausch & Lomb, Bayer Healthcare, Novartis Pharmaceuticals; Payment − manuscript preparation from Novartis Pharmaceuticals.

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