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BACKGROUND: Children born extremely preterm (gestational age < 28 weeks) show reduced visual function even without any cerebral or ophthalmological neonatal diagnosis. In this study, we aimed to assess the retinal structure with optical coherence tomography (OCT) and visual function with pattern-reversal visual evoked potentials (PR-VEPs) in a geographically defined population-based cohort of school-aged children born extremely preterm. Moreover, we aimed to explore the association between measures of retinal structure and visual pathway function in this cohort. METHODS: All children born extremely preterm from 2006-2011 (n = 65) in Central Norway were invited to participate. Thirty-six children (55%) with a median age of 13 years (range = 10-16) were examined with OCT, OCT-angiography (OCT-A), and PR-VEPs. The foveal avascular zone (FAZ) and circularity, central macular vascular density, and flow were measured on OCT-A images. Central retinal thickness, circumpapillary retinal nerve fibre layer (RNFL) and inner plexiform ganglion cell layer (IPGCL) thickness were measured on OCT images. The N70-P100 peak-to-peak amplitude and N70 and P100 latencies were assessed from PR-VEPs. RESULTS: Participants displayed abnormal retinal structure and P100 latencies (≥ 2 SD) compared to reference populations. Moreover, there was a negative correlation between P100 latency in large checks and RNFL (r = -.54, p = .003) and IPGCL (r = -.41, p = .003) thickness. The FAZ was smaller (p = .003), macular vascular density (p = .006) and flow were higher (p = .004), and RNFL (p = .006) and IPGCL (p = .014) were thinner in participants with ROP (n = 7). CONCLUSION: Children born extremely preterm without preterm brain injury sequelae have signs of persistent immaturity of retinal vasculature and neuroretinal layers. Thinner neuroretinal layers are associated with delayed P100 latency, prompting further exploration of the visual pathway development in preterms.
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Potenciais Evocados Visuais , Macula Lutea , Recém-Nascido , Criança , Humanos , Adolescente , Lactente , Lactente Extremamente Prematuro , Vias Visuais , RetinaRESUMO
AIM: To investigate visual function and neurodevelopment in a geographically defined population cohort of school-aged children born extremely preterm. METHODS: All children born extremely preterm in Central Norway between 2006 and 2011 (n=65) were identified, and 36 (median age, min/max: 13, 10/16) were included. Best-corrected visual acuity (BCVA), contrast sensitivity (four spatial frequencies), parent-reported challenges and neuropsychological testing in learning, executive functions, motor skills, perception, reaction time, working and visual memory, processing speed, and pattern separation were measured. Brain MRI (3T) was acquired and read by a neuroradiologist. RESULTS: Median (min/max) BCVA letter score was 85 (35/91) in the better and 82 (13/89) in the worse eye. ROP participants (n=7) had lower contrast sensitivity in the two highest spatial frequencies (p = 0.024 and p = 0.004). Parent-reported challenges correlated negatively with BCVA (learning: p = 0.014; executive functions: p = 0.002; motor skills: p = 0.000; and perception: p = 0.001), while motor skills correlated negatively with one (p = 0.010) and perception with two (p = 0.003 and p = 0.009) of four spatial frequencies. Neuropsychological tests were reduced relative to norms. None had MRI-verified preterm brain injury. CONCLUSION: Visual function was subnormal and correlated with parent-reported challenges in a small cohort of extremely preterm school-aged children, indicating that visual function may be a marker of neurodevelopmental outcomes.
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Lactente Extremamente Prematuro , Destreza Motora , Recém-Nascido , Gravidez , Feminino , Humanos , Criança , Parto , Testes Neuropsicológicos , Função ExecutivaRESUMO
BACKGROUND: Anti-vascular endothelial growth factor is a medicine administered intravitreally by an injection to maintain visual acuity in patients with a variety of retinal diseases. The demand for this treatment has grown considerably in the westernized world the last two decades and will continue to increase due to an aging population. Because of the high volume, injections seize enormous resources and represent high costs for both hospitals and society. Task-shifting of injections from physicians to nurses may be a means to reduce such costs, however the magnitude of possible savings has been poorly investigated. To this end we investigated changes in the hospital costs per injection, six-year cost projections of physician- versus nurse-administered injections for a Norwegian tertiary hospital and we compared the societal costs per patient per year. METHODS: Patients (n = 318) were randomized to either physician- or nurse administered injections, and data were prospectively collected. Hospital costs per injection were calculated as the sum of training costs, personnel time and running expenses. The number of injections for the years 2014 - 21 from a Norwegian tertiary hospital was combined with age group specific injection prevalence and population projections to calculate cost projections for 2022 - 27. Societal costs per patient were calculated as the sum of hospital costs, transport costs for patients, caregivers' use of time, costs of ophthalmology consultations and community-based homecare. RESULTS: The hospital costs per injection were 5.5 higher for physicians compared to nurses (281.6 versus 276.1 ). Cost projections estimated an annual hospital saving of task-shifting of 48 921 for 2022 - 27. Societal costs per patient did not differ significantly between the two groups (mean 4988 vs 5418 , p = 0.398). CONCLUSION: Task-shifting of injections from physicians to nurses can reduce hospital costs and increase the flexibility of physician resources. The annual savings are modest, but increased demand for injections might increase future cost savings. To achieve future savings for society, organizing ophthalmology consultations and injections on the same day to reduce the number of visits might be a solution. TRIAL REGISTRATION: ClinicalTrials.gov NCT02359149 (09/02/2015).
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Médicos , Doenças Retinianas , Humanos , Idoso , Injeções Intravítreas , Centros de Atenção Terciária , Noruega , Análise Custo-BenefícioRESUMO
Research on retinopathy of prematurity (ROP) focuses mainly on the abnormal vascularization patterns that are directly visible for ophthalmologists. However, recent findings indicate that children born prematurely also exhibit changes in the retinal cellular architecture and along the dorsal visual stream, such as structural changes between and within cortical areas. Moreover, perinatal sustained systemic inflammation (SSI) is associated with an increased risk for ROP and the visual deficits that follow. In this paper, we propose that ROP might just be the tip of an iceberg we call visuopathy of prematurity (VOP). The VOP paradigm comprises abnormal vascularization of the retina, alterations in retinal cellular architecture, choroidal degeneration, and abnormalities in the visual pathway, including cortical areas. Furthermore, VOP itself might influence the developmental trajectories of cerebral structures and functions deemed responsible for visual processing, thereby explaining visual deficits among children born preterm.
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Doenças da Coroide , Doenças do Recém-Nascido , Retinopatia da Prematuridade , Criança , Doenças da Coroide/complicações , Humanos , Recém-Nascido , Neovascularização Patológica/complicações , Retina , Retinopatia da Prematuridade/complicaçõesRESUMO
Retinopathy of prematurity (ROP) is an important cause of childhood blindness globally, and the incidence is rising. The disease is characterized by initial arrested retinal vascularization followed by neovascularization and ensuing retinal detachment causing permanent visual loss. Although neovascularization can be effectively treated via retinal laser ablation, it is unknown which children are at risk of entering this vision-threatening phase of the disease. Laser ablation may itself induce visual field deficits, and there is therefore a need to identify targets for novel and less destructive treatments of ROP. Inflammation is considered a key contributor to the pathogenesis of ROP. A large proportion of preterm infants with ROP will have residual visual loss linked to loss of photoreceptor (PR) and the integrity of the retinal pigment epithelium (RPE) in the macular region. Recent studies using animal models of ROP suggest that choroidal degeneration may be associated with a loss of integrity of the outer retina, a phenomenon so far largely undescribed in ROP pathogenesis. In this review, we highlight inflammatory and neuron-derived factors related to ROP progression, as well, potential targets for new treatment strategies. We also introduce choroidal degeneration as a significant cause of residual visual loss following ROP. We propose that ROP should no longer be considered an inner retinal vasculopathy only, but also a disease of choroidal degeneration affecting both retinal pigment epithelium and photoreceptor integrity.
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Doenças da Coroide/metabolismo , Mediadores da Inflamação/metabolismo , Degeneração Neural/metabolismo , Retinopatia da Prematuridade/metabolismo , Animais , Doenças da Coroide/patologia , Doenças da Coroide/terapia , Humanos , Terapia a Laser/tendências , Degeneração Neural/patologia , Degeneração Neural/terapia , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Retinopatia da Prematuridade/patologia , Retinopatia da Prematuridade/terapia , Acuidade Visual/fisiologiaRESUMO
Neonatal hypoxia-ischemia (HI) and the delayed injury cascade that follows involve excitotoxicity, oxidative stress and mitochondrial failure. The susceptibility to excitotoxicity of the neonatal brain may be related to the capacity of astrocytes for glutamate uptake. Furthermore, the neonatal brain is vulnerable to oxidative stress, and the pentose phosphate pathway (PPP) may be of particular importance for limiting this kind of injury. Also, in the neonatal brain, neurons depend upon de novo synthesis of neurotransmitters via pyruvate carboxylase in astrocytes to increase neurotransmitter pools during normal brain development. Several recent publications describing intermediary brain metabolism following neonatal HI have yielded interesting results: (1) Following HI there is a prolonged depression of mitochondrial metabolism in agreement with emerging evidence of mitochondria as vulnerable targets in the delayed injury cascade. (2) Astrocytes, like neurons, are metabolically impaired following HI, and the degree of astrocytic malfunction may be an indicator of the outcome following hypoxic and hypoxic-ischemic brain injury. (3) Glutamate transfer from neurons to astrocytes is not increased following neonatal HI, which may imply that astrocytes fail to upregulate glutamate uptake in response to the massive glutamate release during HI, thus contributing to excitotoxicity. (4) In the neonatal brain, the activity of the PPP is reduced following HI, which may add to the susceptibility of the neonatal brain to oxidative stress. The present review aims to discuss the metabolic temporal alterations observed in the neonatal brain following HI.
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Astrócitos/metabolismo , Encéfalo/metabolismo , Glucose/metabolismo , Hipóxia-Isquemia Encefálica/metabolismo , Neurônios/metabolismo , Animais , Animais Recém-Nascidos , Humanos , RatosRESUMO
Mitochondrial impairment is a key feature underlying neonatal hypoxic-ischemic (HI) brain injury and melatonin is potentially neuroprotective through its effects on mitochondria. In this study, we have used (1) H and (13) C NMR spectroscopy after injection of [1-(13) C]glucose and [1,2-(13) C]acetate to examine neuronal and astrocytic metabolism in the early reperfusion phase after unilateral HI brain injury in 7-day-old rat pups, exploring the effects of HI on mitochondrial function and the potential protective effects of melatonin on brain metabolism. One hour after hypoxia-ischemia, astrocytic metabolism was recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was clearly impaired. Pyruvate carboxylation was also lower in both hemispheres after HI. The transfer of glutamate from neurons to astrocytes was higher whereas the transfer of glutamine from astrocytes to neurons was lower 1 h after HI in the contralateral hemisphere. Neuronal metabolism was equally affected in pups treated with melatonin (10 mg/kg) immediately after HI as in vehicle treated pups indicating that the given dose of melatonin was not capable of protecting the neuronal mitochondria in this early phase after HI brain injury. However, any beneficial effects of melatonin might have been masked by modulatory effects of the solvent dimethyl sulfoxide on cerebral metabolism. Neuronal and astrocytic metabolism was examined by (13) C and (1) H NMR spectroscopy in the early reperfusion phase after unilateral hypoxic-ischemic brain injury and melatonin treatment in neonatal rats. One hour after hypoxia-ischemia astrocytic mitochondrial metabolism had recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was impaired. Melatonin treatment did not show a protective effect on neuronal metabolism.
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Antioxidantes/uso terapêutico , Lesões Encefálicas/etiologia , Lesões Encefálicas/terapia , Isquemia Encefálica/complicações , Melatonina/uso terapêutico , Reperfusão , Acetatos/metabolismo , Animais , Animais Recém-Nascidos , Astrócitos/metabolismo , Lesões Encefálicas/patologia , Modelos Animais de Doenças , Feminino , Lateralidade Funcional/efeitos dos fármacos , Glucose/metabolismo , Isótopos/metabolismo , Espectroscopia de Ressonância Magnética , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/metabolismo , Gravidez , Piruvato Carboxilase/metabolismo , RatosRESUMO
BACKGROUND: Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) now improve or stabilize visual acuity in a number of previously untreatable eye diseases, of which the main are age-related macular degeneration, retinal vein occlusion and diabetic macular edema. Most patients require multiple injections over lengthy periods of time and the prevalence of treatable conditions is increasing. Anti-VEGF IVI normally administered by physicians, therefore represent a considerable workload on ophthalmologic clinics and will continue to do so in the near future. Nurse-administered IVI may relieve this workload, but the safety, cost and patient satisfaction of such an extended role for nurses in ophthalmologic clinics has not earlier been investigated. To investigate these outcomes following independent anti-VEGF IVI by trained nurses, a noninferiority randomized controlled trial is being conducted. METHODS/DESIGN: Patients eligible for anti-VEGF treatment, minimum 304, are recruited and randomized to IVI administration by either trained nurses or physicians. The primary outcome is safety, measured by difference in mean change in visual acuity between the two groups during an observation period of 12 months. Secondary outcomes are incidence of ocular adverse events, cost per patient and patient satisfaction. DISCUSSION: This study protocol describes the design of the first randomized controlled trial of nurse-administered IVI of anti-VEGF. The study is designed to examine safety, cost and patient satisfaction during 12 months follow-up. TRIAL REGISTRATION: ClinicalTrials.gov NCT02359149 . Registered February 4, 2015.
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Inibidores da Angiogênese/administração & dosagem , Injeções Intravítreas/enfermagem , Padrões de Prática em Enfermagem , Doenças Retinianas/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Idoso , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Masculino , Segurança do Paciente , Satisfação do Paciente , Estudos Prospectivos , Doenças Retinianas/enfermagem , Acuidade VisualRESUMO
BACKGROUND AND PURPOSE: Increased susceptibility to excitotoxicity of the neonatal brain after hypoxia-ischemia (HI) may be caused by limited capacity of astrocytes for glutamate uptake, and mitochondrial failure probably plays a key role in the delayed injury cascade. Male infants have poorer outcome than females after HI, possibly linked to differential intermediary metabolism. METHODS: [1-(13)C]glucose and [1,2-(13)C]acetate were injected at zero, 6, and 48 hours after unilateral HI in 7-day-old rats. Intermediary metabolism was analyzed with magnetic resonance spectroscopy. RESULTS: Mitochondrial metabolism was generally reduced in the ipsilateral hemisphere for ≤6 hours after HI, whereas contralaterally, it was reduced in neurons but not in astrocytes. Transfer of glutamate from neurons to astrocytes was increased in the contralateral, but not in the ipsilateral hemisphere at 0 hour, and reduced bilaterally at 6 hours after HI. The transfer of glutamine from astrocytes to glutamatergic neurons was unaltered in both hemispheres, whereas the transfer of glutamine to GABAergic neurons was increased ipsilaterally at 0 hour. Anaplerosis (astrocytes) was decreased, whereas partial pyruvate recycling (astrocytes) was increased directly after HI. Male pups had lower astrocytic mitochondrial metabolism than females immediately after HI, whereas that of females was reduced longer and encompassed both neurons and astrocytes. CONCLUSIONS: The prolonged depression in mitochondrial metabolism indicates that mitochondria are vulnerable targets in the delayed injury after neonatal HI. The degree of astrocytic malfunction may be a valid indicator of outcome after hypoxic/HI brain injury and may be linked to the differential outcome in males and females.
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Astrócitos/metabolismo , Encéfalo/crescimento & desenvolvimento , Hipóxia-Isquemia Encefálica/patologia , Neurônios/metabolismo , Acetatos/química , Animais , Encéfalo/metabolismo , Feminino , Neurônios GABAérgicos/metabolismo , Glucose/química , Glicólise , Espectroscopia de Ressonância Magnética , Masculino , Mitocôndrias/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores Sexuais , Fatores de Tempo , Resultado do TratamentoRESUMO
Glucose and acetate metabolism and the synthesis of amino acid neurotransmitters, anaplerosis, glutamate-glutamine cycling and the pentose phosphate pathway (PPP) have been extensively investigated in the adult, but not the neonatal rat brain. To do this, 7 day postnatal (P7) rats were injected with [1-(13)C]glucose and [1,2-(13)C]acetate and sacrificed 5, 10, 15, 30 and 45 min later. Adult rats were injected and sacrificed after 15 min. To analyse pyruvate carboxylation and PPP activity during development, P7 rats received [1,2-(13)C]glucose and were sacrificed 30 min later. Brain extracts were analysed using (1)H- and (13)C-NMR spectroscopy. Numerous differences in metabolism were found between the neonatal and adult brain. The neonatal brain contained lower levels of glutamate, aspartate and N-acetylaspartate but similar levels of GABA and glutamine per mg tissue. Metabolism of [1-(13)C]glucose at the acetyl CoA stage was reduced much more than that of [1,2-(13)C]acetate. The transfer of glutamate from neurons to astrocytes was much lower while transfer of glutamine from astrocytes to glutamatergic neurons was relatively higher. However, transport of glutamine from astrocytes to GABAergic neurons was lower. Using [1,2-(13)C]glucose it could be shown that despite much lower pyruvate carboxylation, relatively more pyruvate from glycolysis was directed towards anaplerosis than pyruvate dehydrogenation in astrocytes. Moreover, the ratio of PPP/glucose-metabolism was higher. These findings indicate that only the part of the glutamate-glutamine cycle that transfers glutamine from astrocytes to neurons is operating in the neonatal brain and that compared to adults, relatively more glucose is prioritised to PPP and pyruvate carboxylation. Our results may have implications for the capacity to protect the neonatal brain against excitotoxicity and oxidative stress.
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Astrócitos/metabolismo , Encéfalo/metabolismo , Neurônios/metabolismo , Via de Pentose Fosfato/fisiologia , Piruvato Carboxilase/metabolismo , Ácido Pirúvico/metabolismo , Animais , Animais Recém-Nascidos , Encéfalo/crescimento & desenvolvimento , Ácido Glutâmico/metabolismo , Glutamina/administração & dosagem , Glutamina/metabolismo , Neurotransmissores/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE: To explore foveal and parafoveal thickness in adults born preterm with very low birth weight (VLBW) and its association with best-corrected visual acuity (BCVA) and gestational age (GA) compared to adults born at term. METHODS: In a joint study of the Helsinki Study of Very Low Birth Weight Adults (Finland) and the NTNU Low Birth Weight Life study (Norway), 106 VLBW and 143 term-born controls were examined with spectral-domain optical coherence tomography and BCVA at age 31-43 years. Thickness of retinal layers was segmented in the foveal and parafoveal areas of the macula. RESULTS: The total retinal thickness in the foveal area was thicker in VLBW adults compared with controls; mean (SD): 292.5 µm (28.2) and 272.4 µm (20.2); p < 0.001, and thinner in the parafoveal areas of the macula. These findings could be explained by a thicker inner retinal layer in the foveal area found in VLBW adults compared with controls (mean difference 20.4 µm; CI: 15.0 to 25.9), where a thicker fovea was associated with lower GA, but not BCVA. CONCLUSION: Adults born preterm with VLBW had a thicker retina in the foveal area than controls and this was associated with GA, but not with BCVA. These changes seem to be related to a thicker inner retinal layer in VLBW adults. The findings imply that signs of macular underdevelopment are still present in adulthood, but not necessarily related to reduced visual function.
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PURPOSE: The purpose of the study was to investigate visual function and vision-related general health in adults that were born preterm with very low birth weight (VLBW: birth weight < 1500 g) in their 30s-40s. METHODS: We recruited 137 adults born preterm with VLBW and 158 term-born controls aged 31-43 years from two birth cohorts: the Helsinki Study of Very Low Birth Weight Adults (Finland) and the NTNU Low Birth Weight in a Lifetime Perspective study (Norway). We used neonatal data and measured refraction, best-corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, contrast sensitivity, visual fields, intraocular pressure (IOP), self-reported vision-targeted health status with the National Eye Institute Visual Function Questionnaire-25. RESULTS: VLBW adults had a lower BCVA ETDRS score than controls: mean (SD) better eye 86.7 (13.4) versus 90.2 (4.4), p = 0.02; mean (SD) worse eye 82.3 (14.9) versus 87.6 (4.6), p = 0.003. VLBW adults also had lower contrast sensitivity thresholds in several spatial frequencies and scored lower than controls in eight out of the 12 subscales of self-reported vision-targeted health status. Refraction, visual fields and IOP were similar between groups. Two VLBW participants were blind. None had been treated for retinopathy of prematurity. CONCLUSION: We suggest that lower visual function and vision-related health represent life-long consequences of prematurity and VLBW in the studied 31- to 43-year-old cohort. The underlying mechanisms remain to be determined.
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Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Recém-Nascido , Adulto , Humanos , Estudos de Coortes , Visão Ocular , Peso ao NascerRESUMO
Individuals born with very low birth weight (VLBW; < 1500 g) have a higher risk of reduced visual function and brain alterations. In a longitudinal cohort study, we assessed differences in visual outcomes and diffusion metrics from diffusion tensor imaging (DTI) at 3 tesla in the visual white matter pathway and primary visual cortex at age 26 in VLBW adults versus controls and explored whether DTI metrics at 26 years was associated with visual outcomes at 32 years. Thirty-three VLBW adults and 50 term-born controls was included in the study. Visual outcomes included best corrected visual acuity, contrast sensitivity, P100 latency, and retinal nerve fibre layer thickness. Mean diffusivity, axial diffusivity, radial diffusivity, and fractional anisotropy was extracted from seven regions of interest in the visual pathway: splenium, genu, and body of corpus callosum, optic radiations, lateral geniculate nucleus, inferior-fronto occipital fasciculus, and primary visual cortex. On average the VLBW group had lower contrast sensitivity, a thicker retinal nerve fibre layer and higher axial diffusivity and radial diffusivity in genu of corpus callosum and higher radial diffusivity in optic radiations than the control group. Higher fractional anisotropy in corpus callosum areas were associated with better visual function in the VLBW group but not the control group.
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Substância Branca , Recém-Nascido , Adulto , Humanos , Substância Branca/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Estudos Longitudinais , Encéfalo , Recém-Nascido de muito Baixo Peso/fisiologia , AnisotropiaRESUMO
BACKGROUND: Hypoxia-ischemia (HI) induces delayed inflammation and long-term gray and white matter brain injury that may be altered by hyperoxia. METHODS: HI and 2 h of hyperoxia (100% O2) or room air (21% O2) in 7-d-old (P7) rats were studied by magnetic resonance imaging at 7 Tesla during 42 d: apparent diffusion coefficient (ADC) maps on day 1; T(1)-weighted manganese-enhanced images on day 7; diffusion tensor images on days 21 and 42; and T2 maps at all time points. RESULTS: The long-term brain tissue destruction on T2 maps was more severe in HI+hyperoxia than HI+room air. ADC was lower in HI+hyperoxia vs. HI+room air and sham and was correlated with long-term outcome. Manganese enhancement indicating inflammation was seen in both the groups along with more microglial activation in HI+hyperoxia on day 7. Fractional anisotropy (FA) in corpus callosum was lower and radial diffusivity was higher in HI+hyperoxia than that in HI+room air and sham on day 21. From day 21 to day 42, FA and radial diffusivity in HI+hyperoxia were unchanged, whereas in HI+room air, FA increased and radial diffusivity decreased to values similar to sham. CONCLUSION: Hyperoxia caused a more severe tissue destruction, delayed irreversible white matter injury, and increased inflammatory response resulting in a worsening in the trajectory of injury after HI in developing gray and white matter.
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Encéfalo/patologia , Cloretos , Meios de Contraste , Imagem de Tensor de Difusão , Hiperóxia/patologia , Hipóxia-Isquemia Encefálica/patologia , Leucoencefalopatias/patologia , Compostos de Manganês , Animais , Cérebro/patologia , Corpo Caloso/patologia , Modelos Animais de Doenças , Hiperóxia/complicações , Hipóxia-Isquemia Encefálica/complicações , Leucoencefalopatias/etiologia , Ratos , Ratos Wistar , Índice de Gravidade de Doença , Fatores de TempoRESUMO
Doxycycline may potentially be a neuroprotective treatment for neonatal hypoxic-ischemic brain injury through its anti-inflammatory effects. The aim of this study was to examine any long-term neuroprotection by doxycycline treatment on cerebral gray and white matter. Hypoxic-ischemic brain injury was induced in 7-day-old rats. Pups were treated with either doxycycline (HI+doxy) or saline (HI+vehicle) by intraperitoneal injection at 1 h after hypoxia-ischemia (HI). At 6 h after HI, MnCl(2) was injected intraperitoneally for later manganese-enhanced magnetic resonance imaging (MRI). MRI was performed with diffusion-weighted imaging on day 1 and T(1) -weighted imaging and diffusion tensor imaging at 7, 21 and 42 days after HI. Animals were killed after MRI on day 42 and histological examinations of the brains were performed. There was a tendency towards lower lesion volumes on diffusion maps among HI+doxy than HI+vehicle rats at 1 day after HI. Volumetric MRI showed increasing differences between groups with time after HI, with less cyst formation and less cerebral tissue loss among HI+doxy than HI+vehicle pups. HI+doxy pups had less manganese enhancement on day 7 after HI, indicating reduced inflammation. HI+doxy pups had higher fractional anisotropy on diffusion tensor imaging in major white matter tracts in the injured hemisphere than HI+vehicle pups, indicating less injury to white matter and better myelination. Histological examinations supported the MRI results. Lesion size on early MRI was highly correlated with final injury measures. In conclusion, a single dose of doxycycline reduced long-term cerebral tissue loss and white matter injury after neonatal HI, with an increasing effect of treatment with time after injury.
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Cérebro/patologia , Doxiciclina/uso terapêutico , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Animais , Animais Recém-Nascidos , Cérebro/lesões , Modelos Animais de Doenças , Hipóxia-Isquemia Encefálica/patologia , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Manganês/farmacologia , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos WistarRESUMO
OBJECTIVE: Standard treatment of neovascular age-related macular degeneration (nAMD) is intravitreal injections (IVI) of antivascular endothelial growth factor (anti-VEGF) according to treat-and-extend (TnE). Observe-and-plan (OnP), a new regimen based on each individual's relapse interval lead to fewer clinical visits and has so far shown to be safe in treatment-naïve patients. In this study, we explore patient satisfaction and safety in nAMD when switching from TnE to OnP. METHODS AND ANALYSIS: 38 participants treated acording to TnE for ≥12 months were included and switched from TnE to OnP with their last stable interval. Main outcome was patient satisfaction (Leeds Satisfaction Questionnaire). Secondary outcomes were best-corrected visual acuity (BCVA), central retinal thickness (CRT) before and 12 months after switch and number of monitoring visits and injections of anti-VEGF 12 months prior to and following switch. RESULTS: Mean patient satisfaction was higher (3.7±0.5 SD) at 12 months after switch from TnE to OnP than before (3.6±0.5 SD, p=0.009, response rate 76%). BCVA and CRT were unchanged. Number of monitoring visits and injections were lower in the 12 months following than prior to switch (p<0.001). CONCLUSION: A switch from TnE to OnP in a non-treatment-naïve population resulted in higher patient satisfaction, while maintaining stable BCVA. This indicates that OnP may be applicable in the large group of nAMD patients that have received IVI for several years. OnP may alleviate the treatment burden on both individual and society of frequent clinical visits while increasing patient satisfaction.
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Degeneração Macular , Ranibizumab , Inibidores da Angiogênese/uso terapêutico , Humanos , Degeneração Macular/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Satisfação do Paciente , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular , Resultado do Tratamento , Acuidade VisualRESUMO
PURPOSE: To test if task shifting of intraocular injections to nurses in a real-world setting can result in similar visual function outcome with equal safety profile. METHOD: All patients with either age-related macular degeneration, retinal vein occlusion or diabetic macular oedema remitted to intraocular injections at a tertiary ophthalmology department in Norway between March 2015 and May 2017, were asked to participate. The participants were randomized to either nurse- or physician-administered intraocular injections of anti-vascular endothelial growth factor. The primary outcome measure was change in best-corrected visual acuity from baseline to 1-year follow-up. The mean difference in the primary outcome between the groups was analysed by a noninferiority test with a margin of three letters in disfavour of the nurse group. Adverse events were recorded. RESULTS: Three hundred and forty-two patients entered the study. Two hundred and fifty-nine completed the 1-year follow-up and were included in the study sample for the analysis of the primary outcome. Nurse-administered intraocular injections were noninferior to physician-administered injections with 0.7 and 1.6 letters gained, respectively (95% CI of the mean difference, -2.9 to 1.0; p = 0.019, one-sided t-test). Two thousand and seventy-seven injections and three ocular adverse events were recorded. CONCLUSION: Task shifting of intraocular injections to nurses can be performed without increased risk to visual function. Such a task shift can alleviate the burden of performing intraocular injections in ophthalmology departments. To our knowledge, this is the first RCT on task shifting of a surgical procedure from physicians to nurses in a high-income country.
Assuntos
Inibidores da Angiogênese/administração & dosagem , Retinopatia Diabética/tratamento farmacológico , Edema Macular/tratamento farmacológico , Enfermeiras e Enfermeiros/organização & administração , Oftalmologistas/organização & administração , Atenção Primária à Saúde/organização & administração , Oclusão da Veia Retiniana/tratamento farmacológico , Degeneração Macular Exsudativa/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/administração & dosagem , Retinopatia Diabética/fisiopatologia , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Noruega , Satisfação do Paciente , Estudos Prospectivos , Ranibizumab/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Oclusão da Veia Retiniana/fisiopatologia , Método Simples-Cego , Inquéritos e Questionários , Análise e Desempenho de Tarefas , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia , Degeneração Macular Exsudativa/fisiopatologiaRESUMO
Recent findings indicate that retinopathy of prematurity (ROP), presently classified by clinical examinations of retinal vascular tissue, is associated with structural alterations of the central nervous system. Such alterations may be the correlate of the association between ROP and impaired long-term neurocognitive and visual development. The advent of imaging techniques such as structural and diffusion tensor magnetic resonance imaging of the brain, and optical coherence tomography of the retina, will allow the complete visual system to be characterized in greater detail. It has been suggested that ROP may be not only a vascular, but a neurovascular disease, being part of a spectrum that includes pathological development in both the retinal and cerebral neurovascular interphase. We review the present knowledge in the field and point to future directions for research to tackle these questions.
Assuntos
Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Transtornos do Neurodesenvolvimento/etiologia , Retinopatia da Prematuridade/diagnóstico por imagem , Retinopatia da Prematuridade/fisiopatologia , Tomografia de Coerência Óptica , Transtornos da Visão/etiologia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Transtornos do Neurodesenvolvimento/diagnóstico por imagem , Prognóstico , Transtornos da Visão/diagnóstico por imagemRESUMO
Melatonin has potential neuroprotective capabilities after neonatal hypoxia-ischemia (HI), but long-term effects have not been investigated. We hypothesized that melatonin treatment directly after HI could protect against early and delayed brain injury. Unilateral HI brain injury was induced in postnatal day 7 rats. An intraperitoneal injection of either melatonin or vehicle was given at 0, 6 and 25 hours after hypoxia. In-vivo MRI was performed 1, 7, 20 and 43 days after HI, followed by histological analysis. Forelimb asymmetry and memory were assessed at 12-15 and at 36-43 days after HI. More melatonin treated than vehicle treated animals (54.5% vs 15.8%) developed a mild injury characterized by diffusion tensor values, brain volumes, histological scores and behavioral parameters closer to sham. However, on average, melatonin treatment resulted only in a tendency towards milder injury on T2-weighted MRI and apparent diffusion coefficient maps day 1 after HI, and not improved long-term outcome. These results indicate that the melatonin treatment regimen of 3 injections of 10 mg/kg within the first 25 hours only gave a transient and subtle neuroprotective effect, and may not have been sufficient to mitigate long-term brain injury development following HI.