Position Statement
Subject:
Screening for Hydroxychloroquine Retinopathy
Presented
By: Committee on Rheumatologic Care
For Distribution To: Members of the American College
of Rheumatology
Medical Societies
Centers for Medicare and Medicaid Services
Managed Care Organizations/Third-Party Carriers
Arthritis Foundation
Background:
Hydroxychloroquine (Plaquenil) is a commonly used medication in the management of various rheumatic diseases. Standard doses used by rheumatologists are 200mg and 400mg per day. Although serious toxicity with hydroxychloroquine is very unusual, when it does occur it occurs in the form of retinal toxicity. With greater than forty years of experience in monitoring retinal toxicity, the incidence of toxicity has been found to be extremely rare. The American Academy of Ophthalmology has recently reviewed this cumulative experience with hydroxychloroquine and has come out with recommendations for retinal toxicity monitoring. Ophthalmology 2002; 109:1377-82
Several points are important in their review. First, the purpose of monitoring is the recognition of early toxicity and not the prevention of toxicity. Once abnormalities are recognized, toxicity has occurred and it may not reverse. Secondly, there is a strong suggestion from the literature that toxicity is dose and duration related and that the majority of cases have occurred at more than 6.5 mg/kg/day and have occurred at more than 5 years of usage. With more than one million patients using them, less than 20 cases have occurred in doses less than 6.5 mg/kg/day and all occurred with greater than five years of usage. Third, patients who have macular degeneration or retinal dystrophy or who have had previous hydroxychloroquine use may be more susceptible to toxicity or at least present more complicated monitoring problems. Fourth, patients who have severe compromise of renal or hepatic systems might theoretically have more toxicity as the drug is cleared by these two systems, although there is little evidence for this occurring in practice. Finally, obesity may cause an overestimation of the safe dose of hydroxychloroquine because the drug does not accumulate in fat.
POSITION:
Patients beginning hydroxychloroquine therapy should be informed of the possibility, although extremely rare, of retinal toxicity and that periodic monitoring can limit the toxicity by early recognition.
The American Academy of Ophthalmology (AAO) recommends that patients treated with hydroxychloroquine can be divided into two groups: low-risk patients, who receive < 6.5 mg/kg/day of hydroxychloroquine and have used the drug for less than five years, and higher-risk patients, who have used the drug for longer periods, who are taking larger dosages or who have other risk factors such as high body fat level, concomitant kidney or liver disease, concomitant retinal disease or are of an older age (>60 years). All individuals starting these drugs should have a complete baseline ophthalmologic examination within the first year of treatment. This should include examination of the retina through a dilated pupil and testing of central visual field sensitivity by either a self-testing grid chart (Amsler grid) or an automated threshold central visual field testing (Humphrey 10-2 testing). If the patient is in the low-risk category and these examination results are normal, the AAO recommendation is that no further special ophthalmologic testing is needed for the next five years. For patients in the higher- risk category, an annual eye examination is recommended. Should any hint of toxicity appear, more elaborate tests can be performed, such as multifocal electroretinography (mfERG). However, its sensitivity for early screening remains to be determined.
If toxicity is suspected or documented, ideally the drug should be stopped. However, there are situations when this is not an easy decision, e.g., if the impression of toxicity is early or tenuous, or if the treatment has been very effective. Usually, the alternatives to hydroxychloroquine are more toxic therapy and therefore increase the potential of harm. The rheumatologist, ophthalmologist and patient can make a cooperative decision about whether to halt the drug or cautiously continue it with close monitoring of vision function and with the knowledge that some vision could be lost.
Appropriate standards for children and adolescents have not been sufficiently addressed in the available literature. Retinal abnormalities or new interference with vision (including color vision) can be an indication of toxicity and should be discussed with the consulting ophthalmologist on an urgent basis. Use of hydroxychloroquine in children younger than seven years of age may be limited by difficulty in obtaining satisfactory evaluation of color vision in this age group. For this reason, the pediatric age group should receive an annual examination, as a minimum standard of care, until definitive studies in children suggest increasing this monitoring interval.
Approved by Committee on Rheumatologic Care: 02/22/06; 01/11/03
Approved by the Board of Directors: May 2006; 03/07/03
