Long-Term Effects of Iron Chelating Agents on Ocular Function in Patients with Thalassemia Major

Abstract

Background:The aim of this study is to evaluate eye structures and function in patients receiving iron chelating therapy and to assess whether a correlation exists between the onset of ocular alterations and the intake of iron chelating drugs. Methods: A prospective cohort study was performed. Eighty-eight patients, composed of children and adults with thalassemia major (TM) who are taking or had taken iron chelating drugs (deferoxamine, deferiprone or deferasirox), have been initially enrolled in the study. The final sample featured 80 patients, including 18 children and 62 adults. These subjects received an eye examination to evaluate intraocular pressure (IOP), best corrected visual acuity (BCVA), the presence of refractive defects, cornea, anterior chamber, lens, fundus oculi, visual field and mean retinal nerve fiber layer (RNFL) thickness. Logistic regression model analysis was performed in order to assess any correlation. In addition, a literature search regarding the relation between iron chelating drugs and ocular adverse events was carried out to compare the results obtained with the evidence in the literature. Results: Logistic regression did not report a significant correlation between the intake of iron chelating drugs and the onset of anterior ocular segment alterations, lens opacities, retinal diseases, optical neuropathies, astigmatism, visual field and RNFL thickness defects. Logistic regression returned a statistically significant correlation between myopia and iron chelation therapy (p-value 0.04; OR 1.05) and also between presbyopia and total duration of therapy with deferoxamine (p-value 0.03; OR 1.21). Although intraocular pressure levels remained within the normal range, a significant correlation with the length of deferoxamine therapy has been found (p-value 0.002; association coefficient −0.12). A negative correlation between deferiprone and presbyopia has also been observed. Conclusion: Iron chelation therapy is not associated with severe visual function alterations. Limitation of deferoxamine treatment can help prevent ocular complications. Deferiprone and/or deferasirox may be preferable, especially in patients over age 40 years.

Optic neuropathy in iron overload and iron chelation therapy

“…States of systemic iron overaload, such as hereditary hemosiderosis and iron overload secondary to transfusion dependence, are known to be associated with optic neuropathy 1–3 . Similarly, several studies have shown the treatment of such states with chelation therapy, particularly deferoxamine, to be associated with optic neuropathy 4–8 . We report a case of optic neuropathy in a patient with hereditary xerocytosis (HX), an autosomal dominant hemolytic anemia that requires frequent and life‐saving blood transfusions, which resulted in iron overload treated with chelation therapy.…”

“…The available literature shows no adverse ocular events associated with deferiprone. 7,8 Furthermore, our patient was immunosuppressed with tacrolimus, which has been rarely associated with optic neuropathy. 17 Although reported patterns of optic neuropathy in tacrolimus use (i.e., bilateral visual field deficits not respecting the horizontal meridian) are not entirely consistent with our case, its presence may have served as a predisposing factor.…”

“…Deferiprone and deferasirox, more recently developed chelators, have shown more facile forms of administration (oral versus continuous intravenous infusion) and longer half‐lives than that of deferoxamine. The available literature shows no adverse ocular events associated with deferiprone 7,8 …”

“…Deferoxamine has been utilized for transfusion-related iron overload since 1968; however, recent case reports and series have shown an association with toxic retinopathies including pigmentary retinopathy, bull's eye maculopathy, and vitelliform maculopathy. 3,7 Deferiprone and deferasirox, more recently developed chelators, have shown more facile forms of administration (oral versus continuous intravenous infusion) and longer half-lives than that of deferoxamine. The available literature shows no adverse ocular events associated with deferiprone.…”

Iron overload and iron chelating agent exposure in anemia-associated outer retinal degeneration: a case report and review of the literature

“…Several studies, primarily case-reports, have suggested that iron chelators may cause retinopathy [ 3 – 7 ]. However, other studies have presented results that contradict this notion [ 8 , 9 ], and the demonstration of a potential role of trace element imbalance in optic nerve degeneration further complicates the evaluation of visual loss in patients suffering from chronic anemia [ 10 ]. Finally, the potential role of iron in inducing retinal degeneration has received little attention in the context of chronic anemia management.…”