With no risk to the patient, the OCT laser reflects off the eye, permitting close inspection of the nine layers of the retina. Toxicity due to hydroxychloroquine or other antimalarials is manifest in what ophthalmologists call the flying saucer sign or sombrero sign because of its distinctive appearance, the result of fovial thinning and loss of the inner segment/outer segment junction.
scohen125/RetinaGallery
Mild hydroxychloroquine toxicity with the flying saucer sign (center) is seen in this image from an 82-year-old woman who had discontinued the drug for 6 years after taking it for 30 years at 200 mg/day.
Dr. Rosenbaum credited Dr. Michael F. Marmor, professor of ophthalmology at Stanford (Calif.) University, as the driving force behind the new appreciation of the full scope of hydroxychloroquine toxic retinopathy. Dr. Marmor was coauthor of the recent Kaiser Permanente study and has also collaborated with rheumatologist Dr. Fred Wolfe of the National Databank for Rheumatic Diseases in a large study (Arthritis Care Res. 2010;62:775-84). In addition, Dr. Marmor chaired the American Academy of Ophthalmology committee that drew up revised guidelines for screening for hydroxychloroquine retinopathy (Ophthalmology 2011;118:415-22).
Those guidelines call for screening when a patient first goes on hydroxychloroquine and then not again until the 5-year mark, since toxicity is rare within the first 5 years of treatment. After 5 years of use, annual screening is recommended. The screening should include a visual field exam as well as one of the advanced objective technologies: spectral domain OCT, autofluorescence, or multifocal electroretinography. Use of the outmoded Amsler grid is discouraged.
Dr. Rosenbaum advised his colleagues to send their patients to a practitioner who utilizes spectral domain OCT.
“Multifocal ERG is painful, time consuming, and you wouldn’t want to undergo it. Autofluorescence is equally as good as OCT but not as many centers do it; optometrists now often have OCT in their office,” he observed.
The Kaiser Permanente study identified several key risk factors for hydroxychloroquine retinopathy. The investigators were unable to identify a safe dosage of hydroxychloroquine, but they noted that for daily consumption of 4.0-5.0 mg/kg of real body weight, the prevalence was low – less than 2% – for the first 10 years of use. However, the prevalence climbed sharply thereafter. The researchers determined that real body weight predicted risk better than did ideal weight and should be used by clinicians in their dosing calculations. Patients on more than 5.0 mg/kg of real body weight daily had a 5.7-fold greater prevalence of hydroxychloroquine retinopathy.
Chronic kidney disease, defined as an estimated glomerular filtration rate below 60 mL/min, was associated with a twofold increased risk. Concurrent use of tamoxifen – a drug that appears to be toxic to the retina in its own right – was associated with a 4.6-fold increased risk of hydroxychloroquine retinopathy.