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Show Journal of'A] euro- Ophthalmology 21( 1): 32- 33, 2001. © 2001 Lippincott Williams & Wilkins, Inc., Philadelphia Rapid Recovery With Oral Zinc Sulphate in Deferoxamine- induced Presumed Optic Neuropathy and Hearing Loss Antonio Pinna, MD, PhD, Laura Corda, MD, and Francesco Carta, MD Deferoxamine continues to be the mainstay of therapy to remove excess iron in patients requiring long- term transfusions. Overall, deferoxamine has been regarded as having minimal side effects. However, neurotoxicity-related abnormalities, such as optic neuropathy and sensorineural hearing loss, have been described in patients receiving long- term high- dose subcutaneous deferoxamine ( 1- 3). Management of deferoxamine toxicity consists of immediate drug withdrawal. Reversal of toxicity takes weeks to months and does not appear to be related to the deferoxamine dosage and the patient's age. We report a case of deferoxamine- induced presumed optic neuropathy and sensorineural hearing loss. The patient recovered rapidly after treatment with oral zinc sulphate. CASE REPORT A 25- year- old woman with homozygous beta-thalassemia presented with visual loss lasting 2 weeks. She had been regularly transfused since the age of five. Pretransfusional Hb had been maintained in the 11 to 13 g/ dL range in the previous 2 years. She had been taking subcutaneous deferoxamine 2 g/ d ( 50 mg/ kg), 7 days a week, for 3 years in an attempt to achieve a negative iron balance. She has also had mild posttrans-fusional hepatitis C virus ( HCV) chronic hepatitis. On initial examination, her best- corrected visual acuity was 20/ 60 bilaterally. No lens opacities were detected. Fundus examination and fluorescein angiography results were normal OU. The Farnsworth Panel D- 15 test showed an irregular pattern of errors. Automated perimetry revealed bilateral central scotoma. Serum ferritin was 656 ng/ mL ( normal range: 9- 120 ng/ mL), serum iron was 191 ( xg/ dL ( normal range: 40- 160 ( xg/ dL), se- Manuscript received October 16, 2000; accepted December 5, 2000. From the Institute of Ophthalmology ( AP, FC), University of Sas-sari, Sassari, Italy; Department of Ophthalmology ( AP), San Francesco Hospital, Nuoro, Italy; and Centro per le Microcitemie ( LC), San Francesco Hospital, Nuoro, Italy. Address correspondence and reprint requests to Antonio Pinna, MD, PhD, Via Casula 6, 07100 Sassari, Italy; e- mail: oculist@ ssmain. uniss. it. rum calcium was 4.12 mEq/ L ( normal range: 4.5- 5.5 mEq/ L), serum magnesium was 1.6 mg/ dL ( normal range: 1.8- 2.5 mg/ dL), and serum copper was 106 ( xg/ dL ( normal range: 70- 140 ( xg/ dL). Audiometry showed high- frequency sensorineural deficit bilaterally. MRI of the brain and optic nerves was normal. Apart from visual and auditory abnormalities, neurologic examination findings were normal. On the basis of these data, the diagnosis of deferoxamine- induced presumed optic neuropathy and sensorineural hearing loss was made. As a result, deferoxamine was stopped, and oral zinc sulphate ( 100 mg twice daily) was given. After 2 days, visual acuity was 20/ 20 OU, central scotomas disappeared, and color vision and audiogram abnormalities reversed completely. Pretreatment serum zinc levels were not measured, but posttreatment serum zinc was 300 ( xg/ dL ( normal range: 75- 120 ( xg/ dL). Three weeks later, the patient restarted deferoxamine 1.5 g/ d, 6 days a week, and zinc sulphate was tapered to 22.5 mg twice daily. She has had no signs of ocular and auditory toxicity in the 2 years after this incident. DISCUSSION Generalized iron overload resulting from multiple transfusions is common in homozygous beta- thalasse-mia. Since 1962- when administration of intramuscular deferoxamine, a chelating agent that removes iron from ferritin, hemosiderin, and transferrin, was shown to increase urinary iron excretion substantially in patients with thalassemia ( 4)- determined efforts have been made worldwide to administer parenteral deferoxamine in parallel with transfusions. Overall, deferoxamine has not been associated with serious side effects and has been considered minimally toxic in patients with iron loading. Systemic toxic effects include skin flushing at the injection site, urticaria, hypotension, shock and anaphylaxis, reversible nephrotoxicity, and hearing loss. Cataract formation, retinal pigmentary degeneration, and optic neuropathy are the most substantial ocular side effects ( 3). Different mechanisms of possible deferoxamine toxicity include blockade of critical iron- dependent 32 ZINC SUPPLEMENT IN DEFEROXAMINE NEUROTOXICITY 33 enzymes and reduction in critical trace elements other than Fe2+ ( Cu2+, Zn2+, Mg2+, Ca2+) ( 1,5). Evidence indicates that alterations in zinc metabolism may play a role in the pathogenesis of deferoxamine neurotoxicity. Urinary zinc excretion, which is already increased in patients with homozygous beta- thalassemia, may be further increased by usual doses ( 50 mg/ kg) of deferoxamine ( 6,7). Oral zinc supplements with calcium diethylene triamine pentacetic acid ( Ca- DTPA) have been reported to be successful in the management of deferoxamine-induced auditory neurotoxicity ( 8). Moreover, oral zinc sulphate may be beneficial in the management of some toxic optic neuropathies ( 9). In our patient, a presumably toxic origin for the visual and hearing loss was suggested by the bilateral involvement. She was receiving only 50 mg/ kg of deferoxamine, which is generally considered a standard and safe dose, but she had relatively low ferritin levels. It seems likely that toxic deferoxamine levels were attained because the dose was disproportionately high in relation to the amount of iron available for chelation. Similar findings have also been observed by other authors ( 1). We are not aware of any report of toxic optic neuropathy, zinc- related or otherwise, with significant dysfunction to the levels noted, recovering completely in 48 hours. Unfortunately, we were not able to determine pretreatment serum zinc levels. However, because reversal of deferoxamine toxicity after drug withdrawal takes weeks to months, the rapid recovery of visual and auditory abnormalities in our patient suggests that excess deferoxamine may have interfered with zinc metabolism, and oral zinc supplement was beneficial. In conclusion, patients receiving deferoxamine should be closely monitored for ocular and auditory side effects. When such effects are detected, the drug should be discontinued. Oral zinc sulphate may help accelerate neurotoxicity reversal. REFERENCES 1. Olivieri NF, Buncic JR, Chew E, et al. Visual and auditory neurotoxicity in patients receiving subcutaneous deferoxamine infusions. N Engl J Med 1986; 314: 869- 73. 2. Orton RB, de Veber LL, Sulh HM. Ocular and auditory toxicity of long- term, high- dose subcutaneous deferoxamine therapy. Can J Ophthalmol 1985; 20: 153- 6. 3. Lakhapal V, Schocket SS, Jiji R. Deferoxamine ( Desferal ® )- induced toxic retinal pigmentary degeneration and presumed optic neuropathy. Ophthalmology 1984; 91: 443- 51. 4. Sephton- Smith R. Iron excretion in thalassemia major after administration of chelating agents. Br Med J 1962; 2: 1577- 80. 5. Davies SC, Hungerford JL, Arden GB, et al. Ocular toxicity of high- dose intravenous desferrioxamine. Lancet 1983; 2: 181- 4. 6. Uysal Z, Akar N, Kemahli S, et al. Desferrioxamine and urinary zinc excretion in beta- thalassemia major. Pediatr Hematol Oncol 1993; 10: 257- 60. 7. al- Refaie FN, Wonke B, Wickens DG, et al. Zinc concentration in patients with iron overload receiving oral iron chelator 1,2- dimethyl- 3- hydroxypyrid- 4- one or desferrioxamine. J Clin Pathol 1994; 47: 657- 60. 8. Wonke B, Hoffbrand AV, Aldouri M, et al. Reversal of desferrioxamine induced auditory neurotoxicity during treatment with Ca- DTPA. Arch Dis Child 1989; 64: 77- 82. 9. Bechetoille A, Ebran JM, Jallet G. Zinc et neuropathies optiques: de nouvelles perspectives. Bull Soc Opht Fr 1984; 84: 99- 102. J Neuro- Ophthalmol, Vol. 21, No. 1, 2001 |
