Elsevier

Ophthalmology

Volume 118, Issue 2, February 2011, Pages 415-422
Ophthalmology

American Academy of Ophthalmology update
Revised Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy

https://doi.org/10.1016/j.ophtha.2010.11.017Get rights and content

Background

The American Academy of Ophthalmology recommendations for screening of chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy were published in 2002, but improved screening tools and new knowledge about the prevalence of toxicity have appeared in the ensuing years. No treatment exists as yet for this disorder, so it is imperative that patients and their physicians be aware of the best practices for minimizing toxic damage.

Risk of Toxicity

New data have shown that the risk of toxicity increases sharply toward 1% after 5 to 7 years of use, or a cumulative dose of 1000 g, of HCQ. The risk increases further with continued use of the drug.

Dosage

The prior recommendation emphasized dosing by weight. However, most patients are routinely given 400 mg of HCQ daily (or 250 mg CQ). This dose is now considered acceptable, except for individuals of short stature, for whom the dose should be determined on the basis of ideal body weight to avoid overdosage.

Screening Schedule

A baseline examination is advised for patients starting these drugs to serve as a reference point and to rule out maculopathy, which might be a contraindication to their use. Annual screening should begin after 5 years (or sooner if there are unusual risk factors).

Screening Tests

Newer objective tests, such as multifocal electroretinogram (mfERG), spectral domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF), can be more sensitive than visual fields. It is now recommended that along with 10-2 automated fields, at least one of these procedures be used for routine screening where available. When fields are performed independently, even the most subtle 10-2 field changes should be taken seriously and are an indication for evaluation by objective testing. Because mfERG testing is an objective test that evaluates function, it may be used in place of visual fields. Amsler grid testing is no longer recommended. Fundus examinations are advised for documentation, but visible bull's-eye maculopathy is a late change, and the goal of screening is to recognize toxicity at an earlier stage.

Counseling

Patients should be aware of the risk of toxicity and the rationale for screening (to detect early changes and minimize visual loss, not necessarily to prevent it). The drugs should be stopped if possible when toxicity is recognized or strongly suspected, but this is a decision to be made in conjunction with patients and their medical physicians.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Chloroquine and Hydroxychloroquine Toxicity

The mechanism of CQ and HCQ toxicity is not well understood. These drugs have acute effects on the metabolism of retinal cells, including the photoreceptors, but it is not clear whether these short-term metabolic effects are the cause of the slow and chronic damage that characterizes the clinical state of toxicity. Both agents bind to melanin in the retinal pigment epithelium (RPE), and this binding may serve to concentrate the agents and contribute to, or prolong, their toxic effects. However,

Risk of Toxicity

Although no one disputes the potential seriousness of retinal toxicity from these drugs, the rationale (cost-effectiveness) for prospective screening depends on the prevalence of toxicity and the ability to prevent adverse clinical effects (Table 1). The risk of toxicity from CQ and HCQ is low, even after many years of use, but there were little prevalence data in older literature. The largest series of rheumatologic patients showed only 1 case of clear toxicity among 1207 users.9 A smaller

Cumulative Dose

Most reported cases of toxicity have occurred in patients using the drug for more than 7 years or with a cumulative dose that exceeds 1000 g HCQ (or 460 g CQ) (Table 1). The number of reported cases of likely toxicity begins to increase sharply after approximately 5 years of use.10 A cumulative dose of 1000 g HCQ is reached in 7 years with a typical daily dose of 400 mg, and a cumulative dose of 460 g CQ is reached in 5 years with a typical daily dose of 250 mg.

Daily Dose

Older literature (and the

Ophthalmologic Examination

A thorough ophthalmologic examination is important for documentation of visual status and ocular findings. Visual acuity should be measured with best correction in place. The corneal epithelium should be examined to detect verticillata. A dilated fundus examination should be performed and the macula assessed for drusen or pigmentary changes that might be confused with toxicity, with attention to the earliest signs of bull's-eye maculopathy. Pigmentation or atrophy in the periphery and the

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  • Cited by (0)

    Manuscript no. 2010-451.

    Financial Disclosure(s): The author(s) have made the following disclosure(s) for the years 2009 and 2010: Michael Marmor, consultant/advisor, CoMentis, Inc., Eli Lilly and Co., Merck & Co., Inc., Basilea Pharmaceutica, Bayer Corp USA, Johnson & Johnson. Ulrich Kellner, none. Timothy Y. Y. Lai, consultant/advisor, grant support, Novartis Pharmaceuticals; Jonathan S. Lyons, none. William F. Mieler, consultant/advisor, Alcon Laboratories, Allergan, Inc., Genentech, Inc.

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

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