Toxicity of the iron siderophore mycobactin J in mouse macrophages: Evidence for a hypoxia response.

Mycobacterium tuberculosis, the causative agent of tuberculosis, is an obligate intracellular pathogen that lives within the phagosome of macrophages. Here we demonstrate that the siderophore mycobactin J, produced by the closely related intracellular pathogen Mycobacterium paratuberculosis, is toxic to murine macrophage cells. Its median lethal dose, 10 µM, is lower than that of the iron chelators desferrioxamine B and TrenCAM, an enterobactin analog. To determine the source of this toxicity, we conducted microarray, ELISA, and metabolite profiling experiments. The primary response is hypoxia-like, which implies iron starvation as the underlying cause of the toxicity. This observation is consistent with our recent finding that mycobactin J is a stronger iron chelator than had been inferred from previous studies. Mycobactin J is known to partition into cell membranes and hydrophobic organelles indicating that enhanced membrane penetration is also a likely factor. Thus, mycobactin J is shown to be toxic, eliciting a hypoxia-like response under physiological conditions.

Bilateral maculopathy in a thalassemia patient on iron chelation therapy: a case report / Maculopatia bilateral em paciente com talassemia em terapia quelante de ferro: relato de caso

ABSTRACT A 10-year-old Malay girl with underlying HbE/beta-thalassemia, on regular blood transfusion and deferoxamine iron chelation therapy, presented with two-month history of bilateral blurring of vision. On examination, her vision was 6/36 both eyes. Other optic nerve functions were normal. Anterior segment examination of both eyes was unremarkable. Fundus examination of both eyes revealed dull foveal reflex. Optical coherence tomography of both maculae showed increased central subfield thickness. Fundus fluorescence angiography showed patchy hypofluorescence over macular region for both eyes and late staining, indicating retinal pigment epithelium anomalies. A diagnosis of iron-chelation-therapy-related bilateral maculopathy was made. Patient was co-managed with pediatric hematology team to adjust the dose of deferoxamine, and was given three monthly appointments to monitor the progression of maculopathy at the ophthalmology clinic. However patient defaulted ophthalmology follow-up after the first visit.

RESUMO Uma menina malaia de 10 anos de idade com doença de base- B/beta-talassemia, em transfusão de sangue regular e terapia quelante de ferro deferoxamina, apresentou história de dois meses de visão turva bilateral. Ao exame, sua visão era de 6/36 em ambos os olhos. Outras funções do nervo óptico estavam normais. O exame do segmento anterior de ambos os olhos foi normal. Exame do fundo de ambos os olhos revelou reflexo foveal opaco. A tomografia de coerência óptica de ambas as máculas mostrou aumento da espessura do subcampo central. A angiografia de fluorescência do fundo mostrou hipofluorescência irregular sobre a região macular de ambos os olhos e coloração tardia, indicando anomalias de epitélio pigmentar da retina. Um diagnóstico de maculopatia bilateral relacionada à terapia quelante de ferro foi feito. A paciente foi avaliada em conjunto com a equipe de hematologia pediátrica para ajustar a dose de deferoxamina, e foram oferecidas três consultas mensais na clínica oftalmológica, para monitorar a progressão da maculopatia. No entanto, ela não compareceu para acompanhamento oftalmológico após a primeira visita.

Use of deferoxamine (DFO) in transfusion-dependent ß-thalassemia during pregnancy: A retrospective study.

OBJECTIVE: To report cases of use of chelation therapy during pregnancy which resulted in favorable outcomes for the babies. MATERIALS AND METHODS: In this retrospective cohort study, we described the evolution and outcome of 9 pregnancies in Italian thalassemic women who received deferoxamine (DFO) inadvertently during early pregnancy. RESULTS: The use of deferoxamine during first trimester did not lead to adverse effects on the fetus or cause major complications for the gestation, although an increase in iron burden was observed after suspending chelation therapy. CONCLUSION: In our experience, iron-chelation therapy might be administrated in pregnancy where the benefits to the mother outweigh the potential risks to the baby.

Effect of Cefiderocol, a Siderophore Cephalosporin, on QT/QTc Interval in Healthy Adult Subjects.

PURPOSE: Cefiderocol is a novel siderophore cephalosporin with potent activity against gram-negative bacteria, including multidrug-resistant strains. This Phase I study was conducted to assess the tolerability of single-ascending doses of cefiderocol (part 1) and the effect of cefiderocol on cardiac repolarization, assessed using the electrocardiographic corrected QT interval (QTcF) and other ECG parameters (part 2), in healthy adult subjects. METHODS: Part 1 was a randomized, double-blind, placebo-controlled, single-ascending dose study in healthy adult male and female subjects. Part 2 was a 4-period crossover study in which subjects received a single 2-g dose of cefiderocol (therapeutic dose), a single 4-g dose of cefiderocol (supratherapeutic dose), or saline (placebo), each infused over 3 hours, and a single oral 400-mg dose of moxifloxacin. In each treatment period, continuous cardiac monitoring was used to assess the effects of cefiderocol on ECG parameters. The QT interval corrected using the Fridericia formula (QTcF) was the primary ECG parameter; the time-matched placebo- and baseline-adjusted (dd)-QTcF interval was the primary end point. The plasma pharmacokinetic properties of cefiderocol were calculated on the basis of concentration-time profiles in all evaluable subjects. FINDINGS: All point estimates for the ddQTcF interval were <5 ms and the upper bound of the 90% CIs were <10 ms at each timepoint after the initiation of the cefiderocol 3-hour infusion. Concentration-effect modeling showed a slightly negative slope and predicted modestly negative values of the ddQTcF interval at the Cmax of cefiderocol. Both doses of cefiderocol were well tolerated. All adverse events were mild in severity, with no deaths or serious adverse events reported. IMPLICATIONS: Overall, therapeutic and supratherapeutic doses of cefiderocol had no apparent clinically significant effect on the QTcF.

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

BACKGROUND: Deferoxamine (DFO) is one of the most commonly used chelation treatments for transfusional hemosiderosis. Pattern dystrophies constitute a distinct entity of retinal disorders that has been occasionally identified in association with deferoxamine. CASE PRESENTATION: We report two cases of bilateral macular pattern dystrophy in transfusion dependent patients undergoing chronic chelation therapy with deferoxamine due to thalassemias. Our patients were evaluated with multimodal imaging and the results are presented. Both patients had normal cone and rod responses in the full-field electroretinogram and continued the prescribed chelation therapy, after hematology consult. The patients were followed up every 3 months for 2 and 4 years respectively for possible deterioration. Their best corrected visual acuity remained stable with no anatomic change on Optical Coherence Tomography findings. CONCLUSION: Multimodal imaging of our patients allowed a better evaluation and possibly earlier detection of the DFO-related changes. Screening and close follow up of patients under chronic chelating therapy is important in order to promptly diagnose and manage possible toxicity either with discontinuation of the offending agent or dose modification.

Cefiderocol: a novel siderophore cephalosporin.

INTRODUCTION: The emergence of multidrug-resistant bacterial pathogens has led to a global public health emergency and novel therapeutic options and drug-delivery systems are urgently needed. Cefiderocol is a siderophore cephalosporin antibiotic that has recently been developed to combat a variety of bacterial pathogens, including ß-lactam- and carbapenem-resistant organisms. AREAS COVERED: This paper provides an overview of the mutational and plasmid-mediated mechanisms of ß-lactam and carbapenem resistance, the biochemical pathways of siderophores in bacterial iron metabolism, and how cefiderocol may be able to provide better targeted antimicrobial therapy that escape these drug-resistant mechanisms. We also explore the pharmacokinetics of this new compound as well as results from preclinical and clinical studies. EXPERT OPINION: There is an urgent need for novel antimicrobial agents to address the emergence of multidrug-resistant pathogens, which are an increasing cause of morbidity and mortality worldwide. Our understanding of multidrug-resistance and bacterial biochemical pathways continues to expand, and the development of cefiderocol specifically targeting siderophore-mediated iron transport shows potential in escaping mechanisms of drug resistance. Cefiderocol, which demonstrates a favorable side effect profile, has the potential to become first-line therapy for our most aggressive and lethal multidrug-resistant Gram-negative pathogens.

Iron Overload and Chelation Therapy in Non-Transfusion Dependent Thalassemia.

Iron overload (IOL) due to increased intestinal iron absorption constitutes a major clinical problem in patients with non-transfusion-dependent thalassemia (NTDT), which is a cumulative process with advancing age. Current models for iron metabolism in patients with NTDT suggest that suppression of serum hepcidin leads to an increase in iron absorption and subsequent release of iron from the reticuloendothelial system, leading to depletion of macrophage iron, relatively low levels of serum ferritin, and liver iron loading. The consequences of IOL in patients with NTDT are multiple and multifactorial. Accurate and reliable methods of diagnosis and monitoring of body iron levels are essential, and the method of choice for measuring iron accumulation will depend on the patient's needs and on the available facilities. Iron chelation therapy (ICT) remains the backbone of NTDT management and is one of the most effective and practical ways of decreasing morbidity and mortality. The aim of this review is to describe the mechanism of IOL in NTDT, and the clinical complications that can develop as a result, in addition to the current and future therapeutic options available for the management of IOL in NTDT.

Bilateral central serous retinopathy in a patient with paroxysmal nocturnal hemoglobinuria treated with deferoxamine.

PURPOSE: To report a case of acute bilateral central serous retinopathy associated with deferoxamine therapy in the context of paroxysmal nocturnal hemoglobinuria. METHODS: Spectral-domain optical coherence tomography and fundus autofluorescence were used to investigate posterior segment changes. RESULTS: A 76-year-old man with paroxysmal nocturnal hemoglobinuria and hereditary spherocytosis was started on deferoxamine for iron overload secondary to previous blood transfusions. Four days after initiation of treatment, he developed bilateral reduced vision and metamorphopsia. He was noted to have bilateral central serous retinopathy. Symptoms and serous retinal detachment resolved rapidly following discontinuation of treatment. CONCLUSIONS: This case represents the first report of acute bilateral central serous retinopathy associated with deferoxamine therapy. Cessation of deferoxamine resulted in rapid visual recovery.

Effects of deferasirox-deferoxamine on myocardial and liver iron in patients with severe transfusional iron overload.

Deferasirox (DFX) monotherapy is effective for reducing myocardial and liver iron concentrations (LIC), although some patients may require intensive chelation for a limited duration. HYPERION, an open-label single-arm prospective phase 2 study, evaluated combination DFX-deferoxamine (DFO) in patients with severe transfusional myocardial siderosis (myocardial [m] T2* 5-<10 ms; left ventricular ejection fraction [LVEF] ≥56%) followed by optional switch to DFX monotherapy when achieving mT2* >10 ms. Mean dose was 30.5 mg/kg per day DFX and 36.3 mg/kg per day DFO on a 5-day regimen. Geometric mean mT2* ratios (Gmeanmonth12/24/Gmeanbaseline) were 1.09 and 1.30, respectively, increasing from 7.2 ms at baseline (n = 60) to 7.7 ms at 12 (n = 52) and 9.5 ms at 24 months (n = 36). Patients (17 of 60; 28.3%) achieved mT2* ≥10 ms and ≥10% increase from baseline at month 24; 15 switched to monotherapy during the study based on favorable mT2*. LIC decreased substantially from a baseline of 33.4 to 12.8 mg Fe/g dry weight at month 24 (-52%). LVEF remained stable with no new arrhythmias/cardiac failure. Five patients discontinued with mT2* <5 ms and 1 died (suspected central nervous system infection). Safety was consistent with established monotherapies. Results show clinically meaningful improvements in mT2* in about one-third of patients remaining on treatment at month 24, alongside rapid decreases in LIC in this heavily iron-overloaded, difficult-to-treat population. Combination therapy may be useful when rapid LIC reduction is required, regardless of myocardial iron overload. This trial was registered at www.clinicaltrials.gov as #NCT01254227.

Combined chelation therapy with daily oral deferiprone and twice-weekly subcutaneous infusion of desferrioxamine in children with ß-thalassemia: 3-year experience.

OBJECTIVE: To study the efficacy of combined treatment with oral and subcutaneous iron chelators. MATERIAL AND METHODS: 50-100 mg/kg/day of oral deferiprone (DFP) combined with 40 mg/kg/dose s.c. desferrioxamine (DFO) twice weekly were given to transfusion-dependent ß-thalassemia children. RESULTS: Enrolled patients (9 with ß-thalassemia major and 33 with ß-thalassemia hemoglobin E), ranging from 3 to 18 years in age, were divided into 3 groups; group 1 ferritin ≥1,000-2,500 ng/ml (n = 10), group 2 ferritin >2,500-4,000 ng/ml (n = 23) and group 3 ferritin >4,000 ng/ml (n = 9). Of the 42 patients, 28 reached the 36-month follow-up. Ten patients whose ferritin declined <15% while receiving 100 mg/kg/day of DFP were considered nonresponders. The median age and previous transfusion duration before enrollment were significantly higher in nonresponders than responders (p = 0.04 and 0.003, respectively). The responders exhibited a significant fall in median ferritin levels from 2,954.6 to 936.6 ng/ml (p < 0.001). Time to a significant decrease in serum ferritin among responders was 6 months. In 13 patients, 16 episodes of adverse events occurred: hemophagocytosis with cytopenia (n = 1), neutropenia (n = 2), thrombocytopenia (n = 2), elevated alanine aminotransferase (n = 5), elevated serum creatinine (n = 1), proteinuria (n = 1) and gastrointestinal discomfort (n = 4). CONCLUSION: Combination therapy with daily oral DFP and subcutaneous DFO twice weekly is a safe and effective alternative to chelation monotherapy in ß-thalassemia children.

Modified desensitization protocols for a pediatric patient with anaphylactic reaction to deferoxamine.

Thalassemia major is an inherited form of chronic hemolytic anemia that results in iron overload due to regular blood transfusions. Deferoxamine is used as chelating agentfor treatment ofpatients with chronic iron overload worldwide. Anaphylactic reaction to deferoxamine is rare, and the mechanism ofdeferoxamine-induced anaphylaxis is not well understood. Only afewpediatric cases ofsuccessful desensitization for deferoxamine hypersensitivity have been described, and a different protocol has been used in each report. We report a case ofanaphylaxis to deferoxamine in a thirteen-years-old Thai boy with Hemoglobin E/ß-thalassemia disease who underwent successful desensitization. He had been receiving blood transfusions since the age often months. At age eleven, the patient began treatment with deferoxamine. Treatment was interrupted after the occurrence ofanaphylaxis, with urticaria, wheezing and gastrointestinal symptoms. A skin prick test was positive, indicating a type 1 hypersensitivity reaction. Deferoxamine desensitization was attempted with various differentprotocols. Finally, the patient could tolerate deferoxamine therapy at the dose previously administered. We proposed this modified subcutaneous desensitization protocolforpediatric cases that develop allergic reactions to deferoxamine.

Spectral domain optical coherence tomography findings in early deferoxamine maculopathy: report of two cases.

PURPOSE: To describe spectral domain optical coherence tomography features in two cases of early deferoxamine induced retinal toxicity. METHODS: Two patients complained of sudden bilateral visual loss and dyschromatopsia. Both suffered from acute myelocytic leukemia with severe aplastic anemia and were treated with intravenous deferoxamine for 1 month. First ophthalmologic exploration and follow-up included fundoscopic examination, fluorescence angiography, fundus autofluorescence, and spectral domain optical coherence tomography. RESULTS: Initially, both patients presented with a decreased visual acuity, inferior to 20/100. Fundus examination revealed a loss of transparency of the outer retina in the two cases. Autofluorescence pictures displayed hypoautofluorescence in the macular area, whereas fluorescein angiography unveiled an annular hyperfluorescence staining in the macular zone. Spectral domain optical coherence tomography showed a serous detachment of the neuroepithelium associated with photoreceptor outer segment elongation. Deferoxamine toxicity was immediately suspected and therapy promptly interrupted. One week later, both patients recovered visual acuity of 20/20 but retinal pigment epithelium (RPE) mottling was noticed in the macular areas. Spectral domain optical coherence tomography monitoring showed a progressive resolution of serous retinal detachment. Elongation of the photoreceptor outer segment disappeared but the RPE remained thickened, interrupted, and fragmented at different macular loci. CONCLUSION: Serous detachment of the neuroepithelium associated with photoreceptor outer segment elongation in the early stage of deferoxamine maculopathy is described for the first time. Early drug discontinuation allowed a fast resolution of the serous detachment but the typical RPE pigment mottling observed at the resolution phase was noticed 1 week later.

Multimodal imaging in a case of deferoxamine-induced maculopathy.

PURPOSE: To report a case of deferoxamine-induced maculopathy and present the use of multimodal retinal imaging to study this disease entity. METHODS: This is an observational case report of one patient. Multimodal imaging with fundus autofluorescence, infrared imaging, and spectral domain optical coherence tomography was used to investigate the macular changes induced by deferoxamine toxicity. RESULTS: A 53-year-old man with history of ß-thalassemia presented with decreased vision in both eyes 1 month after initiating deferoxamine therapy. Infrared imaging showed areas of increased stippled infrared intensity through the macula. Fundus autofluorescence revealed diffuse areas of stippled hyperautofluorescence and hypoautofluorescence. Spectral domain optical coherence tomography changes included disruption of the ellipsoid zone, attenuation of the photoreceptors, and deposits within the retinal pigment epithelium. CONCLUSION: A case of deferoxamine-induced maculopathy was described and the use of multimodal retinal imaging to study this disease entity was presented.

Deferoxamine retinopathy: spectral domain-optical coherence tomography findings.

BACKGROUND: To describe the spectral domain optical coherence tomography (SD-OCT) findings of a patient who developed pigmentary retinopathy following high-dose deferoxamine administration. CASE PRESENTATION: A 34-year-old man with thalassemia major complained of nyctalopia and decreased vision following high-dose intravenous deferoxamine to treat systemic iron overload. Fundus examination revealed multiple discrete hypo-pigmented lesions at the posterior pole and mid-peripheral retina. Recovery was partial following cessation of desferrioxamine six weeks later. A follow-up SD-OCT showed multiple accumulated hyper-reflective deposits primarily in the choroid, retina pigment epithelium (RPE), and inner segment and outer segment (IS/OS) junction. CONCLUSION: Deferoxamine retinopathy primarily targets the RPE-Bruch membrane-photoreceptor complex, extending from the peri-fovea to the peripheral retina with foveola sparing. An SD-OCT examination can serve as a simple, noninvasive tool for early detection and long-term follow-up.

Multimodal imaging in deferoxamine retinopathy.

PURPOSE: To describe macular lesions in patients with deferoxamine (DFO) retinopathy, and to follow their clinical course using multimodal imaging. METHODS: The authors retrospectively reviewed charts and multimodal imaging of 20 patients with ß-thalassemia diagnosed with DFO retinopathy (40 eyes) after a minimum of 10 years of DFO treatment. Imaging included fundus photography, near-infrared reflectance and fundus autofluorescence imaging on confocal laser scanning ophthalmoscope, and spectral domain optical coherence tomography. RESULTS: Mean age of the 20 patients was 45 years, and mean duration of subcutaneous DFO therapy was 32 years (range, 20-52 years). Ten patients (50%) showed different types of pattern dystrophy-like fundus changes, including butterfly shaped-like (n = 3), fundus flavimaculatus-like (n = 3), fundus pulverulentus-like (n = 3), and vitelliform-like (n = 1) changes. Ten patients (50%) presented only minimal changes in the macula; these patients were significantly younger than patients presenting other patterns (P = 0.023). Confocal laser scanning ophthalmoscope and spectral domain optical coherence tomography showed that these abnormalities were more diverse and widespread than expected by ophthalmoscopy. Abnormal fundus autofluorescence and/or near-infrared reflectance signals corresponded to accumulation of material located within the outer retina or in the Bruch membrane-retinal pigment epithelium (RPE) complex on spectral domain optical coherence tomography. Follow-up examinations during a 40-month period revealed progressive development of RPE atrophy in areas of pattern dystrophy-like changes. CONCLUSION: DFO retinopathy included a variety of pattern dystrophy-like changes or minimal changes affecting the RPE-Bruch membrane-photoreceptor complex. Multimodal imaging demonstrated that fundus changes were more diverse and widespread than expected from ophthalmoscopy. Consistently with previous histologic description of DFO retinopathy, multimodal imaging confirmed that photoreceptor outer-derived retinoids, various fluorophores, and RPE displacement or clumping are involved in DFO retinopathy, finally leading to frank RPE atrophy in most cases of pattern dystrophy-like changes.

High dose deferoxamine in intracerebral hemorrhage (HI-DEF) trial: rationale, design, and methods.

BACKGROUND: Hemoglobin degradation products, in particular iron, have been implicated in secondary neuronal injury following intracerebral hemorrhage (ICH). The iron chelator Deferoxamine Mesylate (DFO) exerts diverse neuroprotective effects, reduces perihematoma edema (PHE) and neuronal damage, and improves functional recovery after experimental ICH. We hypothesize that treatment with DFO could minimize neuronal injury and improve outcome in ICH patients. As a prelude to test this hypothesis, we conducted a Phase I, open-label study to determine the tolerability, safety, and maximum tolerated dose (MTD) of DFO in patients with ICH. Intravenous infusions of DFO in doses up to 62 mg/kg/day (up to a maximum of 6000 mg/day) were well-tolerated and did not seem to increase serious adverse events (SAEs) or mortality. We have initiated a multi-center, double-blind, randomized, placebo-controlled, Phase II clinical trial (High Dose Deferoxamine [HI-DEF] in Intracerebral Hemorrhage) to determine if it is futile to move DFO forward to Phase III efficacy evaluation. METHODS: We will randomize 324 subjects with spontaneous ICH to either DFO at 62 mg/kg/day (up to a maximum daily dose of 6000 mg/day) or saline placebo, given by intravenous infusion for 5 consecutive days. Treatment will be initiated within 24 hours after ICH symptom onset. All subjects will be followed for 3 months and will receive standard of care therapy while participating in the study. At 3 months, the proportion of DFO-treated subjects with a good clinical outcome, assessed by modified Rankin Scale, will be compared to the placebo proportion in a futility analysis. CONCLUSIONS: The Hi-Def trial is expected to advance our understanding of the pathopgysiology of secondary neuronal injury in ICH and will provide a crucial "Go/No Go" signal as to whether a Phase III trial to investigate the efficacy of DFO is warranted.

Desferrioxamine-related ocular toxicity: a case report.

A 29-year-old lady receiving repeated blood transfusions for ß thalassemia since childhood, presented with rapidly deteriorating symptoms of night blindness and peripheral visual field loss. She was recently commenced on high-dose intravenous desferrioxamine for reducing the systemic iron overload. Clinical and investigative findings were consistent with desferrioxamine-related pigmentary retinopathy and optic neuropathy. Recovery was partial following cessation of desferrioxamine. This report highlights the ocular side-effects of desferrioxamine mesylate and the need to be vigilant in patients on high doses of desferrioxamine.

Abnormal fundus autofluorescence results of patients in long-term treatment with deferoxamine.

PURPOSE: To describe and classify patterns of abnormal fundus autofluorescence (FAF) of patients with ß-thalassemia receiving long-term treatment with deferoxamine (DFO). DESIGN: Prospective, cross-sectional, case-control study. PARTICIPANTS: A total of 197 consecutive patients with ß-thalassemia major or intermedia with at least 10 years of treatment with DFO were recruited in a tertiary referral center in Milan, Italy, and were investigated. Seventy-nine thalassemic patients without a history of chelation therapy were included as a control group. METHODS: All of the patients were investigated using best-corrected visual acuity (BCVA), fundus photography, and FAF imaging by confocal scanning laser ophthalmoscopy (cSLO) and were compared with the control group. MAIN OUTCOME MEASURES: Identification of abnormal FAF patterns in thalassemic patients treated with long-term DFO and their progression and relationship with visual function. RESULTS: Abnormal FAF not related to other diseases was observed in 18 of the 197 patients (9%) and was classified into 4 phenotypic patterns: minimal change, focal, patchy, and speckled. The abnormal increased or decreased FAF was bilateral in all the cases, and only in some cases did it correspond to funduscopically visible alterations. There were no FAF abnormalities in the control group. During the follow-up, progressive FAF changes related to retinal pigment epithelium (RPE) damage occurred in the patchy pattern, associated with decreasing BCVA. Patients with speckled and focal patterns showed limited or no changes in FAF during the follow-up. No changes in FAF were found in patients with a minimal change pattern. No treated patient with a normal baseline examination demonstrated FAF changes. Patients with patterns other than the minimal change showed significant BCVA deterioration (P<0.001). CONCLUSIONS: Various phenotypic patterns of abnormal FAF can be identified with cSLO imaging. Fundus autofluorescence is a helpful, fast, and noninvasive tool for monitoring the status of the macula in patients at risk of DFO toxicity. It may be useful in the decision to discontinue or switch the therapy in cases of particular high risk for disease progression. The progressive alteration of the RPE suggests an important role of pathologic RPE changes in the evolution of visual loss during long-term treatment with DFO.

[Myelodysplastic syndrome in the elderly: comprehensive geriatric assessment and therapeutic recommendations]. / Síndrome mielodisplásico en el paciente mayor: valoración geriátrica integral y recomendaciones terapéuticas.

The onset of myelodysplastic syndromes (MDS) is usually around the age of 70. Despite this, most clinical trials are restricted to younger subjects. Thus, the management of elderly patients with MDS is not always optimal. Physiologically, elderly patients show characteristics that differ from those of younger patients and that condition their pharmacological treatment. In this regard, the comprehensive geriatric assessment (CGA) becomes particularly important. This document gathers conclusions from the 1(st) Meeting of Members of the Sociedad Española de Medicina Geriátrica and the Sociedad Española de Hematología y Hemoterapia, with the objective of proposing the establishment of CGA instruments to assist in the decision-making process of elderly patients with MDS. The results of this consensus document will focus on the diagnosis, prognosis, treatment and management of adverse events in this age group.

Efficacy of brinzolamide ophthalmic suspension 1% for treatment of a vitelliform macular lesion in a patient with desferrioxamine retinopathy.

A 46-year-old woman with a vitelliform macular lesion secondary to desferrioxamine retinal toxicity in the right eye was treated with brinzolamide 1% ophthalmic drops three times a day. A spectral-domain optical coherence tomography (SD-OCT) unit was used to monitor any changes in the macular lesion. Two months after starting the eye drops, the SD-OCT showed a notable improvement in the vitelliform macular lesion's thickness. Six months later, further improvement was noted in the macular lesion thickness on SD-OCT testing in the right eye. Best-corrected visual acuity was initially 1.00 logarithm of the minimum angle of resolution (20/200 on a Snellen acuity chart) in the right eye and 0.14 logarithm of the minimum angle of resolution (20/25(-2)) in the left eye. After 6 months of treatment, visual acuity was 0.92 (20/200(+1)) in the right eye and 0.08 (20/25(+1)) in the left eye. The use of brinzolamide 1% was associated with a marked reduction in a vitelliform macular lesion on SD-OCT testing secondary to desferrioxamine retinal toxicity.