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

Georgakopoulos, Constantinos D.; Tsapardoni, Foteini; Kostopoulou, Elli V.; Makri, Olga Ε

doi:10.1186/s12886-018-0911-2

Cited by 9 publications

(5 citation statements)

References 38 publications

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“…DM mesylate stock (Fresenius Kabi) was dissolved in saline at 100 g/L. Doses were extrapolated from human chelation dosing for DM at 9 mL/kg body weight, 17,18 thus providing a total chelator concentration of 26 mmol/L (iron‐binding equivalents), 17,19–21 which was achieved by DM group receiving an intravascular infusion at a concentration of 0.6 mmol/L as adapted from published data 22–24 …”

Section: Methodsmentioning

confidence: 99%

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Novel NMP split liver model recapitulates human IRI and demonstrates ferroptosis modulators as a new therapeutic strategy

Nazzal

Madsen

Armstrong

et al. 2021

Pediatric Transplantation

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Background Almost 9%of deceased donor livers are discarded as marginal donor livers (MDL) due to concern of severe ischemia reperfusion injury (IRI). Emerging data supports ferroptosis (iron regulated hepatocellular death) as an IRI driver, however lack of robust preclinical model limits therapeutic testing. In this manuscript we describe the development of a novel rigorous internal control system utilizing normothermic perfusion of split livers to test ferroptosis regulators modulating IRI. Methods Upon institutional approval, split human MDLs were placed on our normothermic perfusion machine, Perfusion Regulated Organ Therapeutics with Enhanced Controlled Testing (PROTECT), pumping arterial and portal blood. Experiment 1 compared right (UR) and left (UL) lobes to validate PROTECT. Experiment 2 assessed ferroptosis regulator Deferoxamine in Deferoxamine Agent Treated (DMAT) vs. No Agent Internal Control (NAIC) lobes. Liver serology, histology, and ferroptosis genes were assessed. Results Successful MDL perfusion validated PROTECT with no ALT or AST difference between UR and UL (∆ALT UR: 235, ∆ALT UL: 212; ∆AST UR: 576, ∆AST UL: 389). Liver injury markers increased in NAIC vs. DMAT (∆ALT NAIC: 586, ∆ALT DMAT: ‐405; ∆AST NAIC: 617, ∆AST DMAT: ‐380). UR and UL had similar expression of ferroptosis regulators RPL8,HO‐1 and HIFα. Significantly decreased intrahepatic iron (p = .038), HO‐1 and HIFα in DMAT (HO‐1 NAIC: 6.93, HO‐1 DMAT: 2.74; HIFαNAIC: 8.67, HIFαDMAT: 2.60)and no hepatocellular necrosis or immunohistochemical staining (Ki67/Cytokeratin‐7) differences were noted. Conclusion PROTECT demonstrates the therapeutic utility of a novel normothermic perfusion split liver system for drug discovery and rapid translatability of therapeutics, driving a paradigm change in organ recovery and transplant medicine. Our study using human livers, provides preliminary proof of concept for the novel role of ferroptosis regulators in driving IRI.

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Section: Methodsmentioning

confidence: 99%

Section: Dm Dosingmentioning

confidence: 99%

Novel NMP split liver model recapitulates human IRI and demonstrates ferroptosis modulators as a new therapeutic strategy

Nazzal

Madsen

Armstrong

et al. 2021

Pediatric Transplantation

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“…A single case of bilateral central serous chorioretinopathy has also been reported 118. Acutely, patients may have a decrease of vision, develop nyctalopia, ring scotoma, and color vision issues within 10 days of initiating treatment or even many months later 119–123…”

Section: Retinal/rpe Relatedmentioning

confidence: 99%

“…118 Acutely, patients may have a decrease of vision, develop nyctalopia, ring scotoma, and color vision issues within 10 days of initiating treatment or even many months later. [119][120][121][122][123]…”

Section: Symptomsmentioning

confidence: 99%

The Impact of Systemic Medications on Retinal Function

Somisetty

Santina

Sarraf

et al. 2023

Asia-Pacific Journal of Ophthalmology

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This study will provide a thorough review of systemic (and select intravitreal) medications, along with illicit drugs that are capable of causing various patterns of retinal toxicity. The diagnosis is established by taking a thorough medication and drug history, and then by pattern recognition of the clinical retinal changes and multimodal imaging features. Examples of all of these types of toxicity will be thoroughly reviewed, including agents that cause retinal pigment epithelial disruption (hydroxychloroquine, thioridazine, pentosan polysulfate sodium, dideoxyinosine), retinal vascular occlusion (quinine, oral contraceptives), cystoid macular edema/retinal edema (nicotinic acid, sulfa-containing medications, taxels, glitazones), crystalline deposition (tamoxifen, canthaxanthin, methoxyflurane), uveitis, miscellaneous, and subjective visual symptoms (digoxin, sildenafil). The impact of newer chemotherapeutics and immunotherapeutics (tyrosine kinase inhibitor, mitogen-activated protein kinase kinase, checkpoint, anaplastic lymphoma kinase, extracellular signal-regulated kinase inhibitors, and others), will also be thoroughly reviewed. The mechanism of action will be explored in detail when known. When applicable, preventive measures will be discussed, and treatment will be reviewed. Illicit drugs (cannabinoids, cocaine, heroin, methamphetamine, alkyl nitrite), will also be reviewed in terms of the potential impact on retinal function.

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“…deferoxamine) [ 2 , 3 ]. 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 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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Background Deferoxamine retinopathy is the informally designated term used to describe a characteristic pattern of outer retinal degeneration in iron-overloaded chronic anemia patients who are treated with deferoxamine. We hypothesize that insufficiently treated iron overloading and not only deferoxamine is the cause of the retinal degeneration. Our case report is based on exposure histories of two anemia patients and literature review. Case presentation Both anemia patients presented with bilateral visual loss secondary to photoreceptor and retinal pigment epithelium degeneration. Chart review showed that visual loss came after a year-long slow, and rather monotonous rise in plasma ferritin concentrations, with no obvious relation to iron chelator exposure. In one patient, the onset of symptomatic visual loss came after a bout of fever followed by two additional febrile episodes, all accompanied by plasma ferritin spikes. Adjustment of iron chelation therapy did not improve visual function. Experimental studies clearly show that both systemic and intraocular exposure to iron ions can induce retinal degeneration. Conclusion The available evidence indicates that retinal degeneration in chronic anemia patients treated by deferoxamine is cause by insufficient iron chelation, not by deferoxamine. The actual role of iron chelating agents may be to promote a long enough survival to allow the slow development of retinal siderosis.

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

Cited by 9 publications

References 38 publications

Novel NMP split liver model recapitulates human IRI and demonstrates ferroptosis modulators as a new therapeutic strategy

Novel NMP split liver model recapitulates human IRI and demonstrates ferroptosis modulators as a new therapeutic strategy

The Impact of Systemic Medications on Retinal Function

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

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