Royal College of Ophthalmologists : [Eye (1998) 12, 907-909]
Introduction:
Chloroquine and hydroxychloroquine (quinolones) are used primarily by rheumatologists for rheumatology arthritis and systemic lupus erythematosis and by dermatologists for cutaneous lupus. They bind to melanin pigment and interact with nucleic acids (genetic material). Although irreversible retinopathy has been described with the use of the drugs, this has occurred at total doses in excess of those currently recommended. The use of low-dose hydroxychloroquine or the unrelated to antimalarial, Mepacrine, confers minimal risk. Chloroquine should only be considered that if these agents have failed, as there are inadequate data to advise on a safe maximum dose. And the six case series with a total of some 1500 patients treated with hydroxychloroquine, only one case of retinopathy with visual loss was observed. In the largest single series, one patient out of 1207 developed retinopathy after seven years. Where doses of hydroxychloroquine were kept below 6.5 mg per kg per day lean body weight, no cases of toxicity were found in 973 patients followed. However, two cases of retinopathy have been reported when the drug was used for more than six years.
Clinical features:
reversible
irreversible
Is there a case for screening for quinolone toxicity?
Although screening has been recommended, there is no strong evidence that screening is justified. Screening programmes are costly and may generate needless anxiety and work for clinicians. There is no reliable screening test that will identify reversible toxicity before ophthalmoscopic changes develop and the appearance of age-related macular degeneration may be indistinguishable from toxic damage.
Recommendations for good practice in rheumatology and dermatology clinics:
baseline assessment
If no abnormality is detected, treatment with hydroxychloroquine can be commenced.
If visual impairment is present an assessment by an ophthalmologist is advised.
maximum day the dosage recommendations
Hydroxychloroquine 6.5 mg per kilogram lean body weight (usually 400 mg) daily. If the patient is overweight check lean body weight with body mass index calculator.
annual evaluation
Patients should be monitored yearly with note being taken of any visual symptoms, visual acuity measurements and any distortion using the reading chart.
Referral to the ophthalmologist:
Referral to the ophthalmologist is appropriate if any patient:
Children requiring such treatment are likely to be attending the ophthalmologist for slit- lamp examination to exclude uveitis.
Examination by the ophthalmologist:
Assessment should include
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safe criteria: < 5 years: 6.5 mg/kg/day lean body weight in the absence of kidney or liver failure. Cumulative dose < 400 grams (i.e. 2.5 years @ 400 mg/day)
relatively safe: 5-10 years @ < 6.5 mg/kg/day. Cumulative dose < 700 grams. (i.e. 5 yrs at 400 mg/day)
Potentially toxic: > 10yrs or > 6.5 mg/kg/day or > 700 g cumulative dose. (Retinal toxicity has occurred at these levels)
Monitoring Recommendations:
visual acuity, colour vision, slit lamp examination of cornea & retina, central visual field (central 100 by static perimetry or Amsler)
Check cumulative dosage (mg/kg)
Same tests as above
Pattern ERG (if available) tests the ganglion cell layer and is an early indicator of macular dysfunction
>10yrs or >700g cumulative. Advise discontinuation of hydroxychloroquine if practicable or monitor 6 monthly.
The prescribing Medical Practitioner :
should inform each patient of the risks of treatment and the recommended dose,
monitor the dose prescribed (dose/body wgt, cumulative dose, kidney/liver function)
and ensure that ophthalmic examinations occur at the recommended intervals.
Patients must understand that current investigative techniques cannot be guaranteed to detect early, reversible retinopathy and that any retinopathy may progress after cessation of therapy.