Hydroxychloroquine

The 4-aminoquinolines (chloroquine and hydroxychloroquine) are used as second line agents for their disease modifying effect in rheumatoid arthritis and systemic lupus erythematosus. The association between chloroquine therapy and pigmentary maculopathy has been known since 1959.[1] The manufacturer's datasheet suggests that all patients receiving hydroxychloroquine should undergo an ophthalmic examination, including a central visual field test at least twice a year. If implemented this recommendation would have a noticeable impact on the ophthalmic service. Is it necessary?

The earliest sign of chloroquine retinopathy is a paracentral scotoma. This so called premaculopathy can be detected with an Amsler chart.[2] Later, subtle pigmentary mottling develops at die macula, and this may progress to the characteristic bull's eye maculopathy and widespread retinal pigment epithelial atrophy. In its early stages chloroquine retinopathy is reversible by stopping the drug.[3] Hydroxychloroquine given at currently prescribed doses is thought to be less toxic than chloroquine.

The recommended dose for hydroxychloroquine is 6.5 mg/kg lean body weight per day.[4] In their prospective study of 73 patients treated with hydroxychloroquine for at least 18 months, Morsman et al reported one case of possible toxic retinopathy -- and this patient had received twice the recommended daily dose.[5] In a retrospective study of 82 patients taking hydroxychloroquine for over a year (mean 38.6 months) Spalton et al found no cases of retinopathy.[6] No correlation was present between the computerised visual field indices and any measure of increasing drug exposure. The authors concluded that visual field testing was unnecessary in these patients.[6] Bernstein analysed all published cases and Food and Drug Administration reports of hydroxychloroquine retinopathy. He found no evidence of permanent visual loss among more than 1500 patients who did not exceed the recommended daily dosage for up to 10 years.[7] More recently, however, two well documented cases of hydroxychloroquine retinopathy have been reported in patients treated for 6.5 and 8 years without exceeding the recommended maximum daily dose.[8]

The Royal College of Ophthalmologists' guidelines for managing patients receiving hydroxychloroquine recommend a baseline ophthalmic examination at the start of treatment, including best corrected visual acuity, fundoscopy, and a central visual field test.[9] Thereafter the prescribing medical practitioner should be responsible for any screening considered necessary. Patients should be' warned to report any visual disturbance and may be given an Amsler chart to use on a monthly basis. No further ophthalmic examination is necessary. unless the patient becomes symptomatic.

Current evidence suggests that hydroxychloroquine retinopathy is extremely rare if the recommended dose is not exceeded. In most cases a baseline ophthalmic assessment and issue of an Amsler chart with instructions on its use will suffice. The small number of patients who have received hydroxychloroquine for longer than six years should be kept under ophthalmic review until more information is available about the safety of long term treatment.

[1] Hobbs HE, Sorsby A, Freedman A. Retinopathy following chloroquine therapy. Lancet 1959;ii:478-80.

[2] Easterbrook M. The sensitivity of Amsler grid testing in early chloroquine retinopathy. Trans Ophthalmol Soc UK 1985;104:204-7.

[3] Crews SJ. Chloroquine retinopathy with recovery in early stages. Lancet 1964;ii:436-8.

[4] Mackenzie AH. Dose refinemets in long-term therapy of rheumatoid arthritis with antimalarials. Am J Med 1983;75(suppl):40-5.

[5] Morsman CDG, Livesey SJ, Richards IM, Jessop JD, Mills PV. Screening for hydroxychloroquine retinal toxicity: is it necessary? Eye 1990;4:572-6.

[6] Spalton DJ, Roe GMV, Hughes GRV. Hydroxychloroquine dosage parameters and retinopathy. Lupus 1993;2:355-8.

[7] Bernstein HN. Ocular safety of hydroxychloroquine. Ann Opthalmol 1991;23:292-6.

[8] Mavrikakis M, Papazoglou S, Sfikakis PP, Vaiopoulos G.Rouglas K. Retinal toxicity in long term hydroxychloroquine treatment Ann Rheum Dis 1996;55:187-9.

[9] Royal College of Opthalmologists Chloroquine, hydroxychloroquine and the eye.London RCO 1993.

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