Rapid development of severe toxic retinopathy associated with continuous intravenous deferoxamine infusion

Deferoxamine mesylate is a chelating agent used in the treatment of iron overload in patients requiring regular transfusions. Deferoxamine is most commonly administered as a slow subcutaneous infusion but continuous intravenous infusion may be required for treating life threatening cardiac complications due to iron overload.¹ Toxic retinopathy is one of the complications associated with deferoxamine, in which different manifestations including pigmentary retinopathy, bull's eye maculopathy, and vitelliform maculopathy have been described.²,³,⁴,⁵,⁶,⁷,⁸ We report a patient who had rapid development of irreversible diffuse pigmentary retinopathy with severe visual loss while receiving continuous intravenous deferoxamine infusion.

Case report

A 17 year old β thalassaemic patient was referred for ophthalmic assessment with recent onset of colour vision impairment 4 months after commencement of continuous intravenous deferoxamine infusion. He had been on subcutaneous deferoxamine for 14 years but stopped self administration 6 months before presentation. As a consequence of the poor compliance, he developed iron overload with a serum ferritin level of 6370 μg/l, causing dilated cardiomyopathy and arrhythmia. Owing to the severity of the heart condition, he was treated with 44 mg/kg/day (therapeutic index = 0.007) continuous deferoxamine infusion via an indwelling intravenous catheter. On presentation, his visual acuity was 6/18 in both eyes with normal colour vision testing on Ishihara plates. Slit lamp and dilated fundus examinations revealed no abnormality. In view of the severe life threatening cardiac complications, deferoxamine was continued despite the visual symptoms. Three weeks later, his visual acuity deteriorated to counting fingers on reassessment. Fundus examination revealed diffuse pigmentary changes at both macula and peripheral retina (fig 1). Serum ferritin level was found to have decreased to 430 μg/l (therapeutic index = 0.103). Since his heart condition had stabilised, the deferoxamine dosage was reduced to 11 mg/kg/day and later changed to subcutaneous infusion. One year after initial presentation, his visual acuity improved to 6/60 but the diffuse pigmentary retinopathy remained unchanged. Electro‐oculogram showed severely reduced response with Arden ratio of 1.1 bilaterally and full field electroretinogram demonstrated reduced scotopic and photopic response amplitudes with normal implicit times in both eyes.

Figure 1 Fundus photograph of the right eye showing (A) deferoxamine induced toxic retinopathy with diffuse retinal pigmentary changes and areas of hyperpigmentation and hypopigmentation in the macula, with (B) extension of the pigmentary changes to the equatorial region and the peripheral retina areas.

Comment

The use of subcutaneous deferoxamine is generally safe and the development of ocular toxicity is uncommon.³,⁹ However, compliance with subcutaneous therapy may be poor particularly in young patients, and intravenous infusion is sometimes required to treat life threatening complications.¹,⁴ It has been suggested that monthly monitoring of serum ferritin to adjust the deferoxamine dosage below a therapeutic index of 0.025 (daily dose per body weight (mg/kg) divided by serum ferritin level (μg/l)) may prevent deferoxamine related complications.¹⁰ However, this was derived based on ototoxicity and it was unclear whether it applied to ocular toxicity. Our case illustrated the rapid development of severe pigmentary retinopathy over 3 weeks because of a sudden fall in serum ferritin level, which resulted in a therapeutic index four times above the limit. Despite prompt reduction of deferoxamine dosage, the severe pigmentary retinopathy persisted and resulted in irreversible retinal damage with profound visual loss. A previous study on the long term outcome of continuous 24 hour deferoxamine infusion has described a case of reversible retinal toxicity when the therapeutic index was briefly elevated to 0.030.¹ Davies et al also reported the development of pigmentary retinopathy in a patient who had intravenous deferoxamine infusion with a therapeutic index of 0.039 but the visual symptoms resolved after cessation of therapy and the patient's final vision was not affected.⁴ Our case highlighted the importance of frequent serum ferritin level monitoring and maintaining the deferoxamine dosage with therapeutic index <0.025 as severe irreversible retinopathy can develop rapidly. Frequent regular ophthalmic assessments should also be carried out in patients who are on continuous intravenous deferoxamine infusion, as prompt drug discontinuation might potentially arrest the retinal damage.