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D.C. Richa, W.R. Green, J.L. Dunaief; Two Cases of Hereditary Iron Overload Associated With AMD–Related Maculopathy . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3000.
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Purpose: Age–related macular (AMD) degeneration is the leading cause of irreversible blindness in the United States, although the pathogenesis is still not understood. Previous studies have demonstrated an increase in iron levels in post–mortem human AMD eyes when compared with age–matched normal controls (Hahn et al. Arch Ophthalmol. 2003, 121:1099–105). In addition, mice with increased retinal iron levels show increased retinal degeneration with features similar to AMD (Hahn et al. Proc Natl Acad Sci U S A. 2004, 101: 13850–5). These data suggest that iron overload may play a role in the pathogenesis of AMD. To further investigate this, we have studied two patients with hereditary iron overload to determine whether they have features of AMD. Methods: Perls’ staining and DAB enhanced Perls’ staining of a conjunctival biopsy was used to detect elevated iron levels in the conjunctival epithelium in the patient with aceruloplasminemia. In addition, fundus photography, fluorescein angiography, optical coherence tomography, and electroretinography were used to document retinal appearance and function. For the case of hemochromatosis, paraffin sections of formalin fixed post–mortem retinas were studied using Perls' Prussian blue and VIP enhanced Perls' to detect iron. Results: This Caucasian patient with aceruloplasminemia had a maculopathy beginning at age 47. He had development and progression of multiple subretinal yellowish–white deposits and RPE atrophy. To confirm tissue iron overload in this patient, we took the novel approach of a conjunctival biopsy which showed Perls’ Prussian blue positive epithelial cells. The patient with hemochromatosis had drusen that stained for iron with Perls’ Prussian blue. Electron microscopy revealed electron dense deposits (presumably iron) within drusen. The VIP enhanced Perls’ Prussian blue detected iron in the RPE. Conclusions: The demonstration of conjunctival iron overload and presumably retinal iron overload in the patient with aceruloplasminemia in combination with the early–onset of drusen suggest that the iron overload may have been the cause of the maculopathy. Similarly, the patient with hemochromatosis had drusen. Iron was detected in both the drusen and the RPE, suggesting that systemic iron overload or mutation in the hereditary hemochromatosis gene (HFE1) could possibly contribute to AMD. While none of these data prove that iron overload causes AMD, they provide support for this theory of pathogenesis.
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