Do You Need to Screen for Hydroxychloroquine Retinopathy?
Hydroxychloroquine and chloroquine are front-line drugs in the management of rheumatoid and other diseases, and many patients take them on a chronic basis. However, they can be toxic to the retina and have the potential to cause permanent loss of vision. The incidence of retinopathy is very low when patients take less than 6.5 mg/kg/day of hydroxychloroquine or 3 mg/kg/day of chloroquine, and almost unknown within the first 5 years of usage at these dosage levels. Nevertheless occasional patients, most often using higher doses or having used one of the drugs for many years, will develop a distinctive pattern of retinal damage called "bull's eye retinopathy." These drugs accumulate in the melanotic retinal pigment epithelium (RPE) that lies just behind the retina, and gradually damage both RPE and overlying retina. The damage begins somewhat curiously, in areas of retina just off-center (the "parafovea") and becomes visible as a ring-like zone of depigmentation about the foveal center. Thus, visual acuity (which comes from foveal cones) may still be good in the early stages of retinopathy, while there is a zone of impaired sensitivity just off-center. If drug exposure continues, the retinal damage spreads and eventually both center and periphery of the retina can be destroyed. Unfortunately, there is no known treatment for this retinopathy. Once recognized there will virtually always be some degree of permanent visual loss, and the damage may continue to progress long after stopping the drugs (sometimes for years, perhaps because of residual drug deposits in the body).
The dilemma with respect to screening patients that use hydroxychloroquine and chloroquine on a chronic basis (or at high dosages) is that while retinopathy is serious and permanent, its incidence is also very low. What balance of risks, benefits and costs is appropriate for users of these drugs? The PDRŽ recommends quarterly eye examinations (which most would agree is excessive), while a few authors have questioned the propriety of screening (which few would accept as optimal management). The American Academy of Ophthalmology (AAO) recently set up a task force to examine current knowledge about this toxic retinopathy and to make recommendations about the nature and frequency of screening. These may serve as a guide to patients and their medical physicians, but they also serve as a source of information so that patients and general physicians can participate in the decision-making about what screening regimen is most suitable. These recommendations can be found on the web.
The AAO recommendationssuggest that all individuals starting one of these drugs should have a complete baseline ophthalmologic exam within the first year of drug usage. This should include dilated examination of the retina and testing of central visual field sensitivity by either a self-testing grid chart (Amsler grid) or an automated field test (Humphrey 10-2 testing). If the patient is in a "low risk" category with respect to drug dosage and other risk factors, then only routine ophthalmologic testing (as might be advised for anyone at a given age) is recommended for the next 5 years.
It is important to recognize the distinction between "low risk" and "higher risk". From the literature, toxicity is very unlikely in patients taking less than the doses noted above of hydroxychloroquine or chloroquine within the first 5 years. Thus, a 200 mg tablet of hydroxychloroquine daily will be safe for virtually all but the tiniest patients, but a 400 mg daily dosage would put anyone under 135 pounds in the higher risk category. It would be ideal, of course, if all patients could be treated at the lower dose levels. Critical adjustment of hydroxychloroquine dosage is actually rather easy to achieve, even though the tablets come only in two sizes, because the duration of action is so prolonged (from binding within the body) that daily dosage levels can be calculated on a weekly basis (for example, taking two tablets one day, and one the next). However, even patients on these low dose levels would be considered at "higher risk" if they have high body fat levels, associated kidney or liver disease, pre-existing retinal disease, or are greater than 60 years old.
For patients in the higher risk category, which includes anyone using these drugs chronically for more than 5 years, annual eye exams are recommended. Although the incidence of toxicity still remains relatively low, it now becomes harder to predict who may or may not be at risk, and the consequence of missing the early signs of retinopathy can be permanent visual loss. For most patients the screening procedure should be a standard ophthalmologic exam, which includes retinal examination and Amsler grid or Humphrey field testing. Should any hints of toxicity appear, either as symptoms, retinal appearance changes or visual field abnormalities, then more elaborate tests can be performed such as multifocal electroretinography which measures objectively the electrical responses from the central retina.
If toxicity is suspected or documented, these drugs should ideally be stopped. This is not always a simple decision, however, especially if the impression of toxicity is early or tenuous, or if the drugs are effectively controlling a severe or unstable rheumatoid condition. The medical physician and patient should be informed about the ophthalmologic findings and risks so that a cooperative decision can be made about whether to halt drugs or to cautiously continue them with closer monitoring of visual function and with an acceptance of some risk to vision.
It is hoped that these new recommendations will clarify the process of hydroxychloroquine and chloroquine screening, and in particular make it easier during the initial years of usage when the risk is low and when there is likelihood that some patients will not continue on the drug long-term.
AAO Task Force on Recommendations for Screening for Hydroxychloroquine Toxicity:
Dr. Michael F. Marmor
Dr. Ronald Carr
Dr. Michael Easterbrook
Dr. Ayad Farjo
Dr. William Mieler
Patient summaries are available for many of ACP's guidelines and guidance statements.
Request bulk reprints of all guidelines published in Annals of Internal Medicine.
Download ACP's clinical recommendations to your iPhone, iPad, or Android.
Those with other mobile devices can simply visit http://www.acponline.org/mobile/clinicalguidelines/ from your mobile browser to access the Recommendation Summaries in a mobile-friendly format.
Search ACP's complete collection of clinical, ethics, and public policy recommendations.
High Value Care
Access resources and information for ACP's High Value Care initiative.
Access your peers' clinical expertise in our ACP members-only Special Interest Groups virtual community.
ACP Depression Care Guide provides physicians with team-based practices for screening, diagnosis, and management of depression in primary care settings.
Reviews of the World's Top Medical Journals - FREE to ACP Members!
|ACP JournalWiseSM is mobile optimized with optional email alerts! Get access to reviews from over 120 of the world's top medical journals alerting you to the highest quality, most clinically relevant new articles based on your preferred areas of specialty. ACP Members register your FREE account now!|
New CME Option: Internal Medicine 2014 Recordings
New CME Package
|Includes 75 of the most popular sessions in internal medicine and the subspecialties. Stream the sessions, answer brief quizzes and earn CME credit. See details.|