Hydroxychloroquine (Plaquenil) Toxicity

In effect, her lecture was about a toxic retinopathy that takes the classic appearance of bilateral bull’s eye maculopathy. That characteristic appearance is in fact a ring of parafoveal RPE depigmentation that spares the fovea.In passing, she noted that colour vision test and the Amsler grid are not very useful, and in advanced cases, there are losses of VA, peripheral vision, and night vision (nyctalopia). Additionally, there is widespread RPE and general retinal atrophy.A practitioner’s aim should be to detect the probl early, ideally at the pre-RPE loss stage. Classically, there is initial photoreceptor damage in the parafoveal area with the earliest changes most likely to occur in the infero-tporal retina.{{quote-A:R-W:450-Q: A practitioner’s aim should be to detect the probl early, ideally at the pre-RPE loss stage. }}However, in Asian eyes in particular, those early changes often occur in the outer macula area near the vascular arcades – the major vessels above and below the perifovea. The prevalence was given as 7.5% overall by Arnold whereas previously, it was a rare condition.She also stated that there is no completely safe dosage, any deleterious effects are not reversible, and the condition may progress somewhat even after cessation of the medication, especially if not detected early (pre-RPE damage).Key risk factors are daily dosing for some time, concurrent kidney disease, and the concurrent use of tamoxifen, which is usually used for breast cancer. Current recommendations base dosage on actual patient weight but generally, practitioners are advised to limit the dosage to 5 mg/kg body weight/day, although 4 mg/kg/day is preferred.If those recommendations are followed, safety out to 10 years is described as ‘very low risk’. The cumulative risk difference between the 4 mg and 5 mg or more dosages is in favour of the lower amount significantly.Assessment of the visual fields using an automated instrument can show functional damage before it becomes apparent with OCT. A white, 10-2 target was suggested, paying particular attention to the supero-nasal field (inferior-tporal retina) for evidence of early defects.Eventually, the field defect can amount to a ring scotoma. A 24-2 target may be required for some Asian eyes. Both horizontal and vertical OCT scans were recommended and, especially in Asian eyes, scans out to the arcades were suggested. An OCT thickness map was also suggested.Initial damage involves focal interruptions to the photoreceptor lines and localised thinning of the adjacent outer retina. RPE damage follows and, eventually, widespread retinal atrophy. Additional tests include autofluorescence, which maps damage and, late in the process, RPE loss due to the latter’s reduced autofluorescence.MfERG, which is a very sensitive test that confirms suspected visual field losses, was also suggested. Screening recommendations are: Baseline, none for the first five years unless the known risk factors apply, and annual screenings thereafter.As a minimum, screening should include automated visual fields and spectral domain OCT, while autofluorescence and mfERG should be included if available. A standard fundus exam, Amsler grid, colour vision tests, fluorescein angiography, and full-field ERG/EOG are not useful as screening tools.Once a bull’s eye maculopathy is apparent it is too late for a good outcome. If screening test results are suggestive of toxicity, medication should not be stopped precipitously and positive tests repeated. Confirmation with a mfERG and autofluorescence is appropriate.{{image3-a:l-w:1080}}

Dr Jennifer Arnold is a Sydney based medical retinal specialist and researcher. She is a partner at Marsden Eye Specialists with practices in Parramatta, Penrith and Castle Hill. Arnold maintains a strong involvent in clinical research: she has been involved as principal investigator in over 50 international clinical trials of new treatments for a range of retinal conditions and in the analysis of real world outcomes of the managent of retinal.


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