Common Pittfalls Leading to Hydroxychloroquine Retinopathy

Common Pitfalls Leading to Hydroxychloroquine Retinopathy ÊÊÊÊÊÊÊÊÊÊ Ê A 74 year old woman with rheumatoid arthritis was started on hydroxychloroquine 400 mg/d in 2004. She was first referred by her rheumatologist for screening for retinopathy in 2012. She had lost the left eye to trauma as a child. She was 5 ft tall, weighed 198 pounds, and had no renal or liver insufficiency (see figure above). Ê ÊÊÊÊÊÊÊÊÊÊÊ The ophthalmologist who screened her in 2012 found her to have a corrected visual acuity of 20/20 in her right eye and interpreted her 10-2 visual field (VF) and multifocal electroretinogram (mfERG) as normal, although they were not. He did not recognize her toxic dosing and made no recommendation to change it. She was asked to return in 6 months but did not. Ê A different ophthalmologist examined her in 2014. Her corrected visual acuity was 20/20 in the right eye and her fundus examination was normal. A 10-2 VF using a red test object showed progression of an annular scotoma present in 2012. A spectral domain optical coherence tomography (SDOCT) imaging study of the macula showed loss of the parafoveal ellipsoid zone and thinning of the outer nuclear layer. The figure above shows mages of the patient described. A. Note the somatotype. In the short, obese patient, dosing based on ideal body weight, not actual body weight, is appropriate. B. Paracentral scotomata. (red arrow) in her 10-2 visual field test of 2012, missed by her ophthalmologist. C. Annulus of hyperautofluorescence (green arrow) on blue fundus autofluorescence imaging from 2014. D. Reduced paracentral wavelet amplitudes (blue arrow) on multifocal electroretinography. E. Paracentral loss of the ellipsoid line and thinning of the outer nuclear layer (yellow arrow) on spectral domain optical coherence tomography. Ê This case illustrates avoidable, commonly seen traps in the management of the patient taking HC: 1. The rheumatologist prescribed a toxic dose of HC based on the patientÕs height and weight. Commentary: The patient was 5 feet tall, with an ideal body weight of 123 pounds (55.9 kg, see Table 2) and a maximal daily safe dose of 55.9X6.5=363 mg/d of HC. To achieve this using the available pill size of 200 mg, one uses the fact that HC has a long half life (approximately 40 days). Thus one can omit a day of dosing in a week and arrive at a suitable average daily dose. Over a weekÕs duration, this patient can take up to 7X363=2543 mg of HC safely. If she takes 2 tablets per day Monday through Saturday and skips HC on Sunday, her weekly total dose will be 2400 mg which averages out to 2400/7=343 mg/d, which is less than a toxic dose. Ê 2. The patient had no baseline ophthalmic screening examination and was not sent for screening by an ophthalmologist until 8 years into therapy despite having a high risk for toxicity based on her daily dosing. Commentary: AAO guidelines state that a baseline examination should be obtained and then for low risk patients, yearly examinations should begin 5 years later. Ophthalmologists have rejected regularly these recommendations. Rather than continuing to recommend a gap in screening rejected by those tasked with screening for retinopathy, it would be better if the guidelines embrace the practical reality that annual screening is the norm, which in the first years is mainly aimed at detecting and correcting toxic daily dosing. Ê 3. The ophthalmologist failed to recognize and correct the toxic dosing of hydroxychloroquine. Commentary: Toxic dosing is consistently found in 12.8-74.7% of patients taking HC. Correcting toxic daily dosing is the most common action taken by the screening ophthalmologist, and is the main reason to screen patients taking HC. Where safe dosing is assumed, as in Great Britain, screening is not recommended because the rarity of HR in these circumstances makes it a wasteful expense of scarce medical resources. Ê 4. The first ophthalmologist failed to recognize the evidence of toxicity on the initial 10-2 VF. Commentary: The diagnosis of HCR is based on ancillary testing Ð 10-2 VF, SDOCT, mfERG, and fundus autofluorescence imaging. Ophthalmologists who screen for HCR have an obligation to understand what constitutes a positive test, what the potential artifacts are, and how to use multiple modalities to raise clinical confidence in a diagnosis. The topic has been thoroughly explored in multiple publications. Failure to properly interpret testing has formed the basis of large malpractice settlements in missed cases of HCR.