Pseudovitelliform maculopathy associated with deferoxamine toxicity: multimodal imaging and electrophysiology of a rare entity

Abstract

SummaryDeferoxamine is a commonly used chelating agent for secondary hemochromatosis. We report a rare retinal manifestation of deferoxamine toxicity in a 68-year-old man and provide supporting multimodal imaging and electrophysiology. The patient had iron overload related to transfusion-dependent myelodysplastic syndrome and developed a pseudovitelliform macular lesion related to deferoxamine toxicity. We also describe for the first time the worsening of this maculopathy on deferasirox, an alternative chelating agent. Macular pseudovitelliform lesion is a unique manifestation of deferoxamine toxicity that can be mistaken for pattern dystrophy. It is important to recognize this manifestation, because discontinuation of the offending agent may halt or reverse the toxicity. Case ReportA 68-year-old man presented to Atlantis Eyecare for evaluation of blurred vision in both eyes. He endorsed dark adaptation difficulties for 6 months. A year prior to presentation, he was noted by his general ophthalmologist to have a normal fundus examination. His past medical history was notable for myelodysplastic syndrome, for which he received frequent blood transfusions. He had been on deferoxamine for 5 years, presently at 16 g per week, for transfusion-related hemochromatosis. On review of systems, he reported adult-onset hearing loss. He had no family history of retinal degeneration or other pertinent history.On examination, uncorrected Snellen visual acuity was 20/25-2 in the right eye and 20/30-2 in the left eye. Ishihara plates were 4/15 in the right eye and 1/15 in the left eye. There was no afferent pupillary defect. He had bilateral posterior chamber intraocular lenses. Fundus examination revealed healthy appearing optic nerves, but there was diffuse pigment mottling in both maculae, with pseudovitelliform lesions centrally ( Figure 1A). Retinal vessels and periphery were unremarkable.Fundus autofluorescence (FAF) revealed central hypoautofluorescence, with surrounding punctuate increased and decreased autofluorescence in the macula ( Figure 1B). Wide-field FAF did not reveal any abnormalities outside of the maculae ( Figure 1C). Fluorescein angiography (FA) showed blocked fluorescence centrally, with surrounding punctate staining and transmission hyperfluorescence corresponding to the areas of pigment mottling ( Figure 1D). Indocyanine green (ICG) angiography showed increased choroidal vascularity in both maculae ( Figure 1E). Optical coherence tomography (OCT) of the macula revealed vitreomacular adhesion with central subretinal deposits in both eyes (Figure 2A).Kinetic perimetry (Goldmann) revealed superior constriction in both eyes, worse on the right (Figure 3). Electroretinography (ERG) demonstrated a mild-tomoderate reduction in rod function, with relatively preserved cone function of the right eye and normal rod and cone function of the left eye ( Figure 4A and 4B). The electro-oculogram (EOG) was markedly abnormal, with an Arden ratio of 1.3 in each eye ( Figure 4C).Given morphologic and functional evidence of...

Pattern dystrophies in patients treated with deferoxamine: report of two cases and review of the literature

“…Regarding pattern dystrophies, various contradicting electrophysiology findings have been reported in literature (Table 1 ). More specifically, ERG results range from normal [ 3 , 26 ] to impaired cone [ 25 ] or rod responses [ 35 ]. Diffuse dysfunction in EOG has also been reported in one vitelliform case [ 35 ].…”

“…Finally, administration of brinzolamide 0.1% in a patient with vitelliform maculopathy related to DFO resulted in reduction of the macular lesion [ 38 ]. In a recent case report of a pseudovitelliform maculopathy related to DFO, further deterioration occurred after changing the chelator from DFO to deferasirox [ 35 ].…”

Makulopathie bei Sichelzellerkrankung

“…In Zusammenhang mit dem seit fast 60 JahreneingesetztenDeferoxaminwurden RPE-Veränderungen teils mit Akkumulation von Material im Bereich der äußeren Retina, eine Schießscheibenmakulopathie, eine Verdickung der Bruch-Membran und seltener eine pseudovitelliforme Makulopathie beschrieben [10].…”

“…Für das seit 2002 verfügbare Deferasirox wurden milde makuläre Pigmentveränderungen [75], eine perifoveale Verdünnung der äußeren Netzhaut mit Un-terbrechung der ellipsoiden Zone ähnlich frühen OCT-Veränderungen unter Hydroxychloroquin-Einnahme [54] und eine Zunahme einer bereits vorbestehenden Deferoxamin-induzierten pseudovitelliformen Makulopathie nach Wechsel auf Deferasirox [10] beschrieben. Die Häufigkeit des Auftretens einer Makulopathie wird in der Fachinformation mit 1:1000 bis 1:100 angegeben.…”

“…Die Deferoxamin-und Deferasiroxassoziierten Veränderungen und Funktionsstörungen sind nach Absetzen und Dosisreduktion teilweise reversibel. Diskutiert wird, dass die Schädigung auf einem direkten toxischen Effekt auf das RPE beruht oder indirekt auf eine Chelatbildung mit für das RPE essenziellen Spurenelementen (Zink, Kupfer) zurückzuführen ist [10]. Während bei der Makulopathie durchChelatbildnerVeränderungen im Bereich der äußeren Netzhaut…”