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PURPOSE: Mutations of the COL4A1 gene, a major structural protein of vessels, may cause hereditary angiopathy with nephropathy, aneurysms and muscle cramps (HANAC) syndrome. The vascular structure and function of patients with HANAC is poorly known. Here, we report a family with HANAC syndrome associated to a previously unreported mutation in COL4A1. The structure and function of retinal vessels were detailed by adaptive optics ophthalmoscopy (AOO) and optical coherence tomography (OCT) angiography. METHODS: Clinical data from six affected individuals (43 to 72 years old) from a single family comprising two generations were collected. Imaging charts including conventional fundus imaging, OCT-angiography and AOO in static and dynamic (flicker) mode were reviewed. DNA sequencing was done in the proband. RESULTS: DNA sequencing of the proband revealed a heterozygous deletion of COL4A1 (NM_001845) at position 1120 in the intron 20 resulting in the loss of splicing donor site for exon 20 (c.1120 + 2_1120 + 8del heterozygote). Four patients had arterial hypertension, and three had kidney dysfunction, one of which under dialysis. By fundus examination, five had typical retinal arteriolar tortuosity with arteriolar loops. Wall-to-lumen ratio of arteries was within normal limits, that is, lower than expected for hypertensive patients. Several foci of arteriolar irregularities were noted in the two oldest patients. In three affected subjects, evaluation of the neurovascular coupling showed a higher flicker-induced vasodilation than a control population (6 % to 11 %; n < 5 %). CONCLUSIONS: Structural and dynamic analysis of retinal vessels in a HANAC family bearing a previously unreported intronic COL4 mutation was done. In addition to arteriolar tortuosity, we found reduced wall-to-lumen ratio, arteriolar irregularity and increased vasodilatory response to flicker light. These abnormalities were more marked in the oldest subjects. This abnormal flicker response affected also non-tortuous arteries, suggesting that microvascular dysfunction extends beyond tortuosity. Such explorations may help to better vascular dysfunction related to HANAC and hence better understand the mechanisms of end-organ damage.
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Aneurisma , Calambre Muscular , Humanos , Adulto , Persona de Mediana Edad , Anciano , Calambre Muscular/complicaciones , Calambre Muscular/genética , Colágeno Tipo IV/genética , Intrones , Aneurisma/complicaciones , Aneurisma/genética , Vasos Retinianos , Mutación , Tomografía de Coherencia ÓpticaRESUMEN
PURPOSE: The purpose of this study is to evaluate real-world treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) in routine clinical practice in France. METHODS: RAINBOW (NCT02279537) was an ambispective, observational, 4-year study assessing IVT-AFL effectiveness, treatment patterns, and safety in patients with nAMD in France. Treatment-naïve patients prescribed IVT-AFL and treated according to local practice (pro re nata or treat-and-extend) were eligible. Three treatment cohorts were retrospectively identified based on their treatment pattern within the first 12 months: regular (3 initial monthly IVT-AFL injections received within 45-90 days after the first injection in month 0 and followed by injections every 2 months), irregular with the initial monthly injections, and irregular without the initial monthly injections. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline to month 12. The 48-month results are described here. RESULTS: Overall, the study included 516 patients (each with one study eye), and 30.2% of patients completed 48 months of IVT-AFL treatment. Mean change in BCVA from baseline (56.5 letters) to month 48 for patients with an assessment at both time points was + 1.1 (regular cohort, n = 47), + 0.1 (irregular cohort with initial monthly injections, n = 115), and - 1.3 letters (irregular cohort without initial monthly injections, n = 26), representing a decrease from the gains achieved at month 12. Mean number of IVT-AFL injections received by month 48 in the treatment cohorts was 14.9, 13.7, and 11.9, respectively. The safety profile of IVT-AFL was consistent with previous studies. CONCLUSION: In RAINBOW, the 48-month results demonstrate a lack of long-term effectiveness of IVT-AFL treatment of nAMD due to progressive undertreatment in routine clinical practice in France. These real-world findings highlight the importance of 3 initial monthly IVT-AFL injections followed by continuous proactive treatment beyond the first year to achieve optimal functional outcomes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02279537.
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Inhibidores de la Angiogénesis , Degeneración Macular , Humanos , Francia/epidemiología , Inyecciones Intravítreas , Degeneración Macular/tratamiento farmacológico , Ranibizumab , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Agudeza VisualRESUMEN
OBJECTIVES: To evaluate the effectiveness of a home-based simulator training, in comparison with a videogame-based training, in terms of powered wheelchair driving skills, skills use in a real-world setting, and driving confidence. DESIGN: Single-blinded randomized controlled trial. SETTING: Community. PARTICIPANTS: New powered wheelchair users (N=47) randomly allocated to simulator group (n=24, 2 drop-out) and control group (n=23, 3 drop-out). INTERVENTIONS: The miWe wheelchair simulator (simulator group) or a kart driving videogame (control group) was setted-up at participants' homes (computer + joystick). They were instructed to use it at least 20 minutes every 2 days, during a period of 2 weeks. PRIMARY OUTCOME MEASURE(S): Assessments were done at baseline (T1) and post-training (T2) using the Wheelchair Skills Test Questionnaire (WST-Q, version 4.1), Wheelchair Confidence Scale (WheelCon), Assistive Technology Outcomes Profile for Mobility, and Life-Space Assessment (LSA). The time necessary to complete 6 WST tasks was measured with a stopwatch. RESULTS: Participants of the simulator group significantly increased their WST-Q capacity score at T2 by 7.5% (P<.05), whereas the control group remained at the same score (P=.218). Participants of both groups rolled backward and went through a door significantly faster at T2 (P=.007; P=.016), but their speed did not change for the other skills. The WheelCon score significantly increased after training (+4% for the control group and +3.5% for the simulator group, P=.001). There was no T1-T2 difference between groups for the WST-Q performance scores (P=.119), the ATOP-Activity (P=.686), the ATOP-Participation scores (P=.814), and the LSA score (P=.335). No adverse events or side effects were reported during data collection or training. CONCLUSIONS: Participants of both groups improved some skills and their wheelchair driving confidence. The simulator training group also demonstrated a modest post-training gain in their WST-Q capacity, but more studies would be needed to explore the long-term effects of the McGill immersive wheelchair simulator (miWe) simulator on driving skills.
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Silla de Ruedas , Humanos , Encuestas y Cuestionarios , Destreza MotoraRESUMEN
BACKGROUND: Wearable powered exoskeletons represent a promising rehabilitation tool for locomotor training in various populations, including in individuals with a spinal cord injury. The lack of clear evidence on how to implement a locomotor powered exoskeleton training program raises many challenges for patients, clinicians and organizations. OBJECTIVE: To report determinants of implementation in clinical practice of an overground powered exoskeleton locomotor training program for persons with a spinal cord injury. DATA SOURCES: Medline, CINAHL, Web of Science. STUDY SELECTION: Studies were included if they documented determinants of implementation of an overground powered exoskeleton locomotor training program for individuals with spinal cord injury. DATA EXTRACTION: Eligible studies were identified by two independent reviewers. Data were extracted by one reviewer, based on constructs of the Consolidated Framework for Implementation Research, and validated by a second reviewer. RESULTS: Sixty-three articles were included. 49.4% of all determinants identified were related to the intervention characteristics, 29.6% to the individuals' characteristic and 13.5% to the inner setting. Recurrent barriers identified were the high prevalence of adverse events (e.g., skin issues, falls) and device malfunctions. Adequate training for clinicians, time and resource available, as well as discussion about patients' expectations were identified as facilitators. CONCLUSIONS: Powered exoskeleton training is a complex intervention. The limited information on the context and the implementation process domains may represent a barrier to a successful transition from knowledge to action.
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Dispositivo Exoesqueleto , Rehabilitación Neurológica , Traumatismos de la Médula Espinal , Humanos , Modalidades de Fisioterapia , Traumatismos de la Médula Espinal/rehabilitación , CaminataRESUMEN
The Patient Registry for Adolescents and Adults with Stable Fontan Circulation aims to describe a contemporary cohort of Fontan patients who could be eligible for a clinical trial investigating macitentan, an endothelin receptor antagonist. This international, non-interventional, multicentre, cross-sectional, observational registry enrolled patients with "stable" Fontan circulation ≥10 years following extra-cardiac conduit or lateral tunnel procedure. Main exclusion criteria were NYHA functional class IV, reoperation of Fontan circulation, or signs of disease worsening. Patient characteristics at enrolment are described; available data were collected during a single registration visit. Of the 266 screened patients, 254 were included in this analysis. At enrolment, median (interquartile range) age was 24 (20;30) years, 37%/63% of patients were from the USA/Europe, 54% were male, 54%/47% had undergone extra-cardiac conduit/lateral tunnel procedures, and 95% were in NYHA functional class I or II. History of arrhythmia was more common in older patients and patients with lateral tunnel; overall prevalence was 19%. Most laboratory values were within the normal range but mean creatinine clearance was abnormally low (87.7 ml/min). Angiotensin-converting enzyme inhibitors were used by 48% of patients and their use was associated with creatinine clearance <90 ml/min (p = 0.007), as was Fontan completion at an older age (p = 0.007). 53.4% of patients had clinical characteristics that could potentially meet an endothelin receptor antagonist trial's eligibility criteria. The PREpArE-Fontan registry describes a cohort of patients who could potentially participate in an endothelin receptor antagonist trial and identified early subtle signs of Fontan failure, even in "stable" patients.
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Procedimiento de Fontan , Cardiopatías Congénitas , Adolescente , Adulto , Anciano , Creatinina , Estudios Transversales , Antagonistas de los Receptores de Endotelina , Femenino , Procedimiento de Fontan/efectos adversos , Cardiopatías Congénitas/diagnóstico , Humanos , Masculino , Sistema de Registros , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Background and Objectives: Long-term hydroxychloroquine (HCQ) therapy can lead to retinal toxicity. Typically, it is characterized by a bull's eye maculopathy. More recently, a "pericentral" form of HCQ retinopathy that predominantly affects patients of Asian descent has been described. To our knowledge, this is the first reported case where such an asymmetry between the right and the left eye in the toxicity profile is observed. Case presentation: The patient presented with a 12-year exposure to HCQ at a daily dose of 4.35 mg/kg. She presented an inferior pericentral-only phenotype of HCQ toxicity on the right eye and a perifoveal-only toxicity on the left eye. Modest progression of toxicity was observed on both eyes over the seven years of follow-up, despite drug discontinuation. Conclusions: To our knowledge, this is the first time that two different phenotypes of HCQ-related retinopathy are found in the same patient, challenging our understanding of the pathophysiology of HCQ retinal toxicity.
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Antirreumáticos , Degeneración Macular , Enfermedades de la Retina , Antirreumáticos/toxicidad , Femenino , Humanos , Hidroxicloroquina/efectos adversos , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/tratamiento farmacológico , Tomografía de Coherencia ÓpticaRESUMEN
Most studies addressing the role of vestibulospinal reflexes in balance maintenance have mainly focused on responses in the lower limbs, while limited attention has been paid to the output in trunk and back muscles. To address this issue, we tested whether electromyographic (EMG) responses to galvanic vestibular stimulations (GVS) were modulated similarly in back and leg muscles, in situations where the leg muscle responses to GVS are known to be attenuated. Body sway and surface EMG signals were recorded in the paraspinal and limb muscles of humans (n = 19) under three complementary conditions. During treadmill locomotion, EMG responses in the lower limbs were observed only during stance, whereas responses in trunk muscles were observed during all phases of the locomotor cycle. During upright standing, a slight head contact abolished the responses in the lower limbs, while the responses remained present in back muscles. Similarly, during parabolic flight-induced microgravity, EMG responses in lower limb muscles were suppressed but remained in axial muscles despite the abolished gravitational otolithic drive. Our results suggest a differentiated control of axial and appendicular muscles when a perturbation is detected by vestibular inputs. The persistence and low modulation of axial muscle responses suggests that a hard-wired reflex is functionally efficient to maintain posture. By contrast, the ankle responses to GVS occur only in balance tasks when proprioceptive feedback is congruent. This study using GVS in microgravity is the first to present an approach delineating feedforward vestibular control in unconstrained environment.NEW & NOTEWORTHY This study addresses the extent of conservation of trunk muscle control in humans. Results show that galvanic vestibular stimulation-evoked vestibular responses in trunk muscles remain strong in conditions where leg muscle responses are downmodulated (walking, standing, microgravity). This suggests a phylogenetically conserved blueprint of sensorimotor organization, with strongly hardwired vestibulospinal inputs to axial motoneurons and a higher degree of flexibility in the later emerging limb control system.
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Pierna/fisiología , Neuronas Motoras/fisiología , Músculo Esquelético/fisiología , Equilibrio Postural/fisiología , Reflejo/fisiología , Médula Espinal/fisiología , Vestíbulo del Laberinto/fisiología , Adulto , Estimulación Eléctrica , Electromiografía , Humanos , Músculos Paraespinales/fisiologíaRESUMEN
PURPOSE: To report the effectiveness of intravitreal aflibercept (IVT-AFL) treatment for diabetic macular edema (DME) in French clinical practice. METHODS: APOLLON (NCT02924311) was a prospective, observational cohort study of patients with DME. Effectiveness was evaluated by change from baseline in best-corrected visual acuity (BCVA) at 12 months in treatment-naïve patients (i.e., had not received any anti-vascular endothelial growth factor [anti-VEGF] agent, laser, or steroid at IVT-AFL treatment start) and previously treated patients (i.e., previously treated with anti-VEGF agents other than IVT-AFL, laser, or steroids at IVT-AFL treatment start). Secondary endpoints included change in central retinal thickness (CRT) over 12 months, frequency of injections, and proportion of patients with safety events. RESULTS: Of the 147 patients followed for at least 12 months and included in the effectiveness analysis, 52.4% (n = 77) were treatment-naïve and 47.6% (n = 70) were previously treated. Mean (standard deviation [SD]) BCVA score at baseline was 62.7 (14.3) Early Treatment Diabetic Retinopathy Study (ETDRS) letters in treatment-naïve patients and 60.0 (13.7) ETDRS letters in previously treated patients. At month 12, mean (SD) change in BCVA was + 7.8 (12.3) letters in treatment-naïve patients and + 5.0 (11.3) letters in previously treated patients. Mean CRT decreased in both patient cohorts. The mean (SD) number of IVT-AFL injections at month 12 was 7.6 (2.5) for treatment-naïve patients and 7.6 (2.3) for previously treated patients. Of 388 patients included in the safety analysis, ocular treatment-emergent adverse events occurred in 54.1% (n = 210) of patients. CONCLUSION: IVT-AFL treatment was associated with improvements in functional and anatomic outcomes in both treatment-naïve and previously treated patients with DME in France.
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Retinopatía Diabética/tratamiento farmacológico , Edema Macular/tratamiento farmacológico , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Agudeza Visual , Anciano , Retinopatía Diabética/complicaciones , Retinopatía Diabética/epidemiología , Femenino , Estudios de Seguimiento , Francia/epidemiología , Humanos , Incidencia , Inyecciones Intravítreas , Edema Macular/epidemiología , Edema Macular/etiología , Masculino , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: To review treatment outcomes from real-world data of patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) injection. METHODS: RAINBOW (ClinicalTrials.gov, NCT02279537) is an ongoing, observational, 4-year study to monitor the effectiveness and safety of IVT-AFL in patients with nAMD in clinical practice in France. Treatment-naïve patients diagnosed with nAMD who had been prescribed IVT-AFL by their treating physician were eligible. The regimens of interest were regular treatment interval cohort (patients who received three initial monthly IVT-AFL injections followed by regular injections every 2 months) and two irregular treatment interval cohorts (with and without three initial monthly injections). Here we describe results at 24 months in patients according to IVT-AFL treatment regimen. RESULTS: The mean change in best-corrected visual acuity (BCVA) with IVT-AFL from baseline to 24 months was + 3.0 letters in the overall population (P < 0.05 vs baseline). The mean change was positive for the regular and irregular treatment interval cohorts with initial doses (+ 4.9 and + 4.0 letters, respectively; P < 0.05 vs baseline) and negative for the irregular treatment interval cohort without initial doses (- 2.5 letters; P = 0.365 vs baseline) at 24 months. The mean overall number of IVT-AFL injections over 12 and 24 months was 6.0 and 8.8, respectively. The most common ocular adverse events were lack of efficacy (6.3%), vitreous floaters (2.7%), and increased lacrimation (1.7%). CONCLUSIONS: In the real-world RAINBOW study, visual outcomes observed at 24 months were consistent with results from the primary endpoint at 12 months. In this study, treatment-naïve patients who received three initial IVT-AFL doses and regular IVT-AFL treatment over the first 24 months experienced better visual outcomes than patients who received no initial doses and an irregular treatment regimen. TRIAL REGISTRATION: www.ClinicalTrials.gov (NCT02279537). Registered 29 October 2014.
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Inhibidores de la Angiogénesis/administración & dosificación , Neovascularización Coroidal/tratamiento farmacológico , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Degeneración Macular Húmeda/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/efectos adversos , Neovascularización Coroidal/diagnóstico por imagen , Neovascularización Coroidal/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intravítreas , Masculino , Proteínas Recombinantes de Fusión/efectos adversos , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Agudeza Visual/fisiología , Degeneración Macular Húmeda/diagnóstico por imagen , Degeneración Macular Húmeda/fisiopatologíaRESUMEN
Inherited retinal disorders (IRD) represent clinically and genetically heterogeneous diseases. To date, pathogenic variants have been identified in ~260 genes. Albeit that many genes are implicated in IRD, for 30-50% of the cases, the gene defect is unknown. These cases may be explained by novel gene defects, by overlooked structural variants, by variants in intronic, promoter or more distant regulatory regions, and represent synonymous variants of known genes contributing to the dysfunction of the respective proteins. Patients with one subgroup of IRD, namely incomplete congenital stationary night blindness (icCSNB), show a very specific phenotype. The major cause of this condition is the presence of a hemizygous pathogenic variant in CACNA1F. A comprehensive study applying direct Sanger sequencing of the gene-coding regions, exome and genome sequencing applied to a large cohort of patients with a clinical diagnosis of icCSNB revealed indeed that seven of the 189 CACNA1F-related cases have intronic and synonymous disease-causing variants leading to missplicing as validated by minigene approaches. These findings highlight that gene-locus sequencing may be a very efficient method in detecting disease-causing variants in clinically well-characterized patients with a diagnosis of IRD, like icCSNB.
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Canales de Calcio Tipo L/genética , Enfermedades Hereditarias del Ojo/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Mutación , Miopía/genética , Ceguera Nocturna/genética , Análisis de Secuencia de ADN/métodos , Predisposición Genética a la Enfermedad , Hemicigoto , Humanos , Intrones , Masculino , Linaje , Empalme del ARN , Mutación SilenciosaRESUMEN
PURPOSE: The purpose of this study is to report a case of ritonavir-related retinal toxicity followed over a year. Electrophysiological features and multimodal imaging, including adaptive optics, are provided and discussed. METHODS: Electrophysiological recordings and multimodal imaging were performed and repeated over 1 year. RESULTS: Fundus examination revealed crystalline maculopathy in conjunction with pigment disruption. Spectral domain optical coherence tomography displayed thinning of the macula without cysts. Autofluorescence imaging revealed a mixed pattern of complete loss of the autofluorescence in the area of retinal pigment deposit and an increased transmission of the autofluorescence in the area of retinal thinning. Fluorescein angiography ruled out parafoveal telangiectasia. Indocyanine green angiography was not contributive. Increased spacing of the macular cone mosaic, crystal deposits and pigment migrations were seen with adaptive optics. Full-field electroretinogram was slightly reduced for both eyes, especially in the light-adapted responses, and mfERG confirmed bilateral maculopathy. Functional and structural abnormalities did not change with follow-up besides constant pigmentary changes monitored with adaptive optics. CONCLUSION: Ritonavir-related retinal toxicity is a maculopathy with peculiar features including crystalline and pigment migration associated with central or temporofoveolar thinning and inconstant macular telangiectasia. Despite drug cessation, retinal remodelling continues to progress.
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Inhibidores de la Proteasa del VIH/efectos adversos , Enfermedades de la Retina/inducido químicamente , Ritonavir/efectos adversos , Electrorretinografía , Angiografía con Fluoresceína/métodos , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal , Enfermedades de la Retina/diagnóstico , Pigmentos Retinianos/metabolismo , Tomografía de Coherencia Óptica/métodosRESUMEN
Bone cells exposed to real microgravity display alterations of their cytoskeleton and focal adhesions, two major mechanosensitive structures. These structures are controlled by small GTPases of the Ras homology (Rho) family. We investigated the effects of RhoA, Rac1, and Cdc42 modulation of osteoblastic cells under microgravity conditions. Human MG-63 osteoblast-like cells silenced for RhoGTPases were cultured in the automated Biobox bioreactor (European Space Agency) aboard the Foton M3 satellite and compared to replicate ground-based controls. The cells were fixed after 69 h of microgravity exposure for postflight analysis of focal contacts, F-actin polymerization, vascular endothelial growth factor (VEGF) expression, and matrix targeting. We found that RhoA silencing did not affect sensitivity to microgravity but that Rac1 and, to a lesser extent, Cdc42 abrogation was particularly efficient in counteracting the spaceflight-related reduction of the number of focal contacts [-50% in silenced, scrambled (SiScr) controls vs. -15% for SiRac1], the number of F-actin fibers (-60% in SiScr controls vs. -10% for SiRac1), and the depletion of matrix-bound VEGF (-40% in SiScr controls vs. -8% for SiRac1). Collectively, these data point out the role of the VEGF/Rho GTPase axis in mechanosensing and validate Rac1-mediated signaling pathways as potential targets for counteracting microgravity effects.
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Fenómenos Fisiológicos Celulares , Osteoblastos/metabolismo , ARN Interferente Pequeño/genética , Ingravidez , Proteína de Unión al GTP cdc42/metabolismo , Proteína de Unión al GTP rac1/metabolismo , Proteína de Unión al GTP rhoA/metabolismo , Actinas/metabolismo , Células Cultivadas , Citoesqueleto/metabolismo , Sensación de Gravedad , Humanos , Mecanotransducción Celular , Microtúbulos/metabolismo , Osteoblastos/citología , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Vuelo Espacial , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteína de Unión al GTP cdc42/antagonistas & inhibidores , Proteína de Unión al GTP cdc42/genética , Proteína de Unión al GTP rac1/antagonistas & inhibidores , Proteína de Unión al GTP rac1/genética , Proteína de Unión al GTP rhoA/antagonistas & inhibidores , Proteína de Unión al GTP rhoA/genéticaRESUMEN
PURPOSE: We report the clinical findings and retinal function of a patient who presented retinal toxicity signs after cefuroxime use for a phacoemulsification surgery. METHODS: A 64-year-old man underwent a technically uneventful left eye cataract surgery. A standard intracameral dose of cefuroxime (0.1 mL of 10.0 mg/mL solution) was administered at the end of the surgery. RESULTS: At review 2 days later, he complained about left eye visual loss. Fundus examination revealed a diffuse retinal pallor with small intraretinal cysts. Optical coherence tomography scans showed a large retinal serous detachment with a schisis-like appearance of the outer nuclear layer. A slight global retinal dysfunction was recorded on ISCEV full-field electroretinogram. Fast clinical recovery was observed. Optical coherence tomography scans were back to normal within less than a week. Two months later, full-field electroretinogram showed no longer abnormalities. CONCLUSION: It is the first report to our knowledge of a case of retinal toxicity with a standard dose. Kinetics and studies about cefuroxime toxicity are reviewed and discussed.
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Cámara Anterior/efectos de los fármacos , Antibacterianos/toxicidad , Cefuroxima/toxicidad , Facoemulsificación , Retina/efectos de los fármacos , Enfermedades de la Retina/inducido químicamente , Electrorretinografía , Endoftalmitis/prevención & control , Angiografía con Fluoresceína , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Retina/diagnóstico , Tomografía de Coherencia ÓpticaRESUMEN
PURPOSE: To report the first documented case of aripiprazole-induced chorioretinopathy. METHODS AND RESULTS: A 47-year-old schizophrenic patient with loss of vision due to an atypical retinopathy was investigated. She had been treated with aripiprazole for 8 years. Multimodal imaging showed in the right eye a large area of retinal atrophy predominating in the outer retina, including the posterior pole up to the upper temporal periphery, and in the left eye a serous retinal detachment. The electroretinogram exhibited decreased and delayed responses of both the rod and cone systems; the electrooculogram showed no light peak. CONCLUSION: Aripiprazole, an atypical antipsychotic, was introduced more recently than the antipsychotics commonly incriminated in chorioretinopathies, such as thioridazine. Optical coherence tomography was not used to document former cases of antipsychotic-related chorioretinopathies. Although pathophysiological mechanisms are poorly understood, imaging of the present case points toward an involvement of the retinal pigmentary epithelium. Clinicians should be aware of the potential chorioretinal toxicity of new atypical antipsychotics.
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Antipsicóticos/efectos adversos , Electrorretinografía , Imagen Multimodal , Piperazinas/efectos adversos , Quinolonas/efectos adversos , Retina/fisiopatología , Enfermedades de la Retina/inducido químicamente , Aripiprazol , Colorantes , Adaptación a la Oscuridad , Electrooculografía , Femenino , Angiografía con Fluoresceína , Humanos , Verde de Indocianina , Persona de Mediana Edad , Enfermedades de la Retina/fisiopatología , Epitelio Pigmentado de la Retina , Esquizofrenia/tratamiento farmacológico , Tomografía de Coherencia Óptica , Agudeza Visual/efectos de los fármacosRESUMEN
PURPOSE: To report new findings in a case of ocular siderosis explored by high resolution angiography and adaptive optics (AO). METHODS: We report data on a 40-year-old man with an intraocular foreign body (IOFB) embedded in the sclera after hammering. RESULTS: Nine months after this accident, the patient presented with full-field electroretinogram (FF-ERG) abnormalities. Subsequent IOFB extraction was performed. One month after the surgery, high resolution angiography showed for the first time small iron particles all over the inner retinal surface. Spreading of these deposits was followed by inflammatory prepapillary new vessels and venous retinal vasculatis, which spontaneously resolved within a few months. ERG responses became slightly electronegative at this time. Clearance of the iron particles was followed over a year with AO and ERG recording. AO revealed an arterial tropism with a decrease in the amount of particles overtime, which may be consistent with macrophagic activity. CONCLUSION: High resolution angiography and AO are new tools, combined with electrophysiology, to better understand ocular siderosis pathophysiology.
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Cuerpos Extraños en el Ojo/diagnóstico , Lesiones Oculares Penetrantes/diagnóstico , Hierro , Retina/fisiopatología , Enfermedades de la Retina/diagnóstico , Esclerótica/lesiones , Siderosis/diagnóstico , Adulto , Electrorretinografía , Cuerpos Extraños en el Ojo/fisiopatología , Cuerpos Extraños en el Ojo/cirugía , Lesiones Oculares Penetrantes/fisiopatología , Lesiones Oculares Penetrantes/cirugía , Humanos , Masculino , Enfermedades de la Retina/fisiopatología , Enfermedades de la Retina/cirugía , Siderosis/fisiopatología , Siderosis/cirugía , Tomografía de Coherencia Óptica , Agudeza Visual , VitrectomíaRESUMEN
Many lifestyle factors, such as nutritional imbalance leading to obesity, metabolic disorders, and nutritional deficiency, have been identified as potential risk factors for male infertility. The aim of this study was to evaluate the relationship between semen parameters and anthropometric, metabolic and nutritional parameters. Relationship was first assessed individually, then after the application of a previously constructed and validated machine learning score that allows their combination. Anthropometric, metabolic, antioxidant, micronutrient, and sperm parameters from 75 men suffering from idiopathic infertility from four infertility centers in France (Jean-Verdier ART Center Hospital, Bondy; North Hospital ART Center, Saint-Étienne; Navarre Polyclinic ART Center, Pau; and Cochin Hospital ART Center, Paris) between September 2009 and December 2013 were collected. After assessing standard correlation analysis, a previously built machine learning model, providing a score ranging from 0 (the poorest) to 1 (the most favorable), was calculated for each man in the study cohort. This machine learning model, which separates infertile/fertile men with unexplained infertility on the basis of their bioclinical signature, provides a more holistic evaluation of the influence of the considered markers (anthropometric, metabolic, and oxidative status). We observed a significant correlation of some anthropometric, metabolic, and nutritional disorders with some sperm characteristics. Moreover, an unfavorable machine learning score was associated with a high level of sperm DNA fragmentation. Favorable anthropometric, metabolic, and oxidative patterns, which may reflect an appropriate lifestyle, appear to positively impact overall health, in particular reproductive function. This study, consistent with previous publications, suggests that beyond semen quality parameters, in an essential assessment of male fertility, other key factors should be taken into account. In this regard, the application of emerging artificial intelligence techniques may provide a unique opportunity to integrate all these parameters and deliver personalized care.
Asunto(s)
Infertilidad Masculina , Aprendizaje Automático , Estado Nutricional , Análisis de Semen , Humanos , Masculino , Adulto , Infertilidad Masculina/etiología , Antropometría , Motilidad Espermática , Semen/metabolismoRESUMEN
INTRODUCTION: Didanosine is an adenosine analog, part of the nucleoside reverse-transcriptase inhibitor family. Since the description of didanosine-induced retinopathy in the early 1990s, little is known about the progression of this toxic retinopathy and the putative underlying mitochondrial defect. OBJECTIVES: We report long-term follow-up for cases of didanosine-induced retinopathy and discuss a new hypothesis for pathophysiology based on the alteration of endogenous adenosine on the photoreceptor outer segment turnover and phagocytosis by the retinal pigment epithelium. METHODS: Ophthalmic data from six cases (12 eyes) of didanosine-induced retinopathy from a single institution were retrospectively analyzed. RESULTS: All patients displayed bilateral retinal alterations in the mid-periphery. Despite didanosine discontinuation, patients with advanced areas of patchy chorioretinal atrophy appeared to have a faster progression than those with limited lesions. Full-field electroretinogram revealed generalized rod-cone dysfunction in most cases that remained stable over time. CONCLUSION: We propose new guidelines including early screening and long-term observations.
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Didanosina , Humanos , Estudios de Seguimiento , Estudios RetrospectivosRESUMEN
PURPOSE: To report a case of late contralateral recurrence of unilateral acute idiopathic maculopathy (UAIM) and its sequelae by using adaptive optics. METHODS: A 46-year-old woman positive for coxsackie virus presented with a typical UAIM, followed 3 years later by a recurrence in the fellow eye. At an early stage, spectral domain-OCT showed a localized loss of the inner segment/outer segment and cone outer segment tips lines, while flood-illumination adaptive optics displayed pigment clumpings and transient small hard exudates, associated with a persistent blurring of the cone mosaic. RESULTS: These findings support the hypothesis of an outer retinal blood-barrier breakdown, inducing a disruption limited to the outer segment of the photoreceptors, followed by a progressive though incomplete normalization of the cone mosaic characterized by a persistent misalignment of outer segment tips. CONCLUSION: This would explain the acute clinical presentation of UAIM, followed by a spontaneous, partial, recovery, with a relative scotoma remaining over time.
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Degeneración Macular , Enfermedades de la Retina , Femenino , Angiografía con Fluoresceína , Humanos , Persona de Mediana Edad , Enfermedades de la Retina/diagnóstico , Tomografía de Coherencia Óptica , Agudeza VisualRESUMEN
PURPOSE: To report a new toxic retinopathy related to the use of hair dye. METHODS: Case reports of three patients with follow-up after exposure and until resolution. RESULTS: There were three middle-aged women (32-66 year old) all of whom had bilateral moderate to severe vision loss and normal slit-lamp examination at presentation. Fundus examination showed bilateral multiple serous retinal detachments predominantly located in the posterior pole, with some pigment epithelial hypertrophy in chronic cases. Optical coherence tomography showed similar features as in MEK-inhibitor retinopathy. Electrooculogram performed in one patient showed abnormal Arden ratio. During follow-up, visual acuity improved with regression of the serous retinal detachments. The speed of resolution was proportional to the acuteness of the exposure to aromatic amines. CONCLUSION: Hair dyes containing aromatic amines can be responsible for bilateral toxic retinopathy mimicking MEK-inhibitor retinopathy.
Asunto(s)
Tinturas para el Cabello , Desprendimiento de Retina , Enfermedades de la Retina , Adulto , Anciano , Aminas/efectos adversos , Femenino , Angiografía con Fluoresceína , Tinturas para el Cabello/efectos adversos , Humanos , Persona de Mediana Edad , Quinasas de Proteína Quinasa Activadas por Mitógenos/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos , Desprendimiento de Retina/diagnóstico , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/complicaciones , Enfermedades de la Retina/diagnóstico , Tomografía de Coherencia ÓpticaRESUMEN
APOLLON (NCT02924311) was a prospective observational study to evaluate the effectiveness of intravitreal aflibercept (IVT-AFL) treatment of diabetic macular edema (DME) over 24 months in routine clinical practice in France. The primary endpoint was mean change from baseline in best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study letters) by 12 months, and safety was monitored throughout the study. Of 402 patients enrolled across 61 participating clinics and hospitals in France, 168 patients were followed for at least 24 months and included in the effectiveness analyses (79 treatment-naïve and 89 previously treated). After 24 months of IVT-AFL treatment, the mean (± standard deviation [SD]) change in BCVA from baseline was + 6.5 (± 10.7) letters in treatment-naïve patients (p < 0.001) and + 1.6 (± 17.0) letters in previously treated patients (p = 0.415) from a baseline of 63.8 (± 13.6) and 60.5 (± 16.5) letters. The mean number of IVT-AFL treatments over 24 months was 11.3 (± 4.9) and 11.9 (± 4.7) for treatment-naïve and previously treated patients. This final analysis of the APOLLON study indicated that following 24 months of IVT-AFL treatment in routine clinical practice in France, treatment-naïve patients with DME achieved significant gains in visual acuity and previously treated patients maintained prior visual acuity gains.Trial registration number: NCT02924311.