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1.
Life Sci ; 256: 117935, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32526286

RESUMO

AIMS: Retinal ischemia/reperfusion (I/R) injury is common in the development of ophthalmic diseases and potentially causes blindness. In present study, the aim is to investigate the possible protective effects of puerarin on retinal I/R. MAIN METHODS: Retinal I/R injury was conducted on the left eyes of male Sprague Dawley rats, which were subsequently received treatment with puerarin. After administration, retinal I/R-induced apoptosis, oxidative stress and inflammatory responses were detected. Meanwhile, we purified retinal ganglion cells (RGCs) from 7-day-old rats. After subjected RGCs to oxygen and glucose deprivation/reoxygenation (OGD/R), apoptosis and TLR4/NLRP3 inflammasome activation in RGCs were detected. KEY FINDINGS: Puerarin prominently suppressed apoptosis, alleviated oxidative stress and suppressed TLR4/NLRP3 inflammasome activation in rats with retinal I/R injury. Consistent with our in vivo study, we found puerarin ameliorated retinal I/R injury through suppressing apoptosis and TLR4/NLRP3 inflammasome activation in RGCs. SIGNIFICANCE: Our findings reveal that puerarin plays a protective role against retinal I/R injury by alleviating RGC damage, and is beneficial for the treatment of I/R injury-caused ophthalmic diseases.


Assuntos
Isoflavonas/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Doenças Retinianas/tratamento farmacológico , Células Ganglionares da Retina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Humanos , Inflamassomos/metabolismo , Masculino , Modelos Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Retina/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo
4.
Graefes Arch Clin Exp Ophthalmol ; 258(6): 1149-1156, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: covidwho-121183

RESUMO

PURPOSE: There is an urgent need to address how to best provide ophthalmic care for patients with retinal disease receiving intravitreal injections with anti-vascular endothelial growth factor agents during the ongoing global COVID-19 pandemic. This article provides guidance for ophthalmologists on how to deliver the best possible care for patients while minimizing the risk of infection. METHODS: The Vision Academy's Steering Committee of international retinal disease experts convened to discuss key considerations for managing patients with retinal disease during the COVID-19 pandemic. After reviewing the existing literature on the issue, members put forward recommendations that were systematically refined and voted on to develop this guidance. RESULTS: The considerations focus on the implementation of steps to minimize the exposure of patients and healthcare staff to COVID-19. These include the use of personal protective equipment, adherence to scrupulous hygiene and disinfection protocols, pre-screening to identify symptomatic patients, and reducing the number of people in waiting rooms. Other important measures include triaging of patients to identify those at the greatest risk of irreversible vision loss and prioritization of treatment visits over monitoring visits where possible. In order to limit patient exposure, ophthalmologists should refrain from using treatment regimens that require frequent monitoring. CONCLUSION: Management of patients with retinal disease receiving intravitreal injections during the COVID-19 pandemic will require adjustment to regular clinical practice to minimize the risk of exposure of patients and healthcare staff, and to prioritize those with the greatest medical need. The safety of patients and healthcare staff should be of paramount importance in all decision-making.


Assuntos
Infecções por Coronavirus/prevenção & controle , Injeções Intravítreas , Oftalmologia/organização & administração , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Doenças Retinianas/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Betacoronavirus , Desinfecção , Humanos , Equipamento de Proteção Individual
5.
Graefes Arch Clin Exp Ophthalmol ; 258(6): 1149-1156, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32328757

RESUMO

PURPOSE: There is an urgent need to address how to best provide ophthalmic care for patients with retinal disease receiving intravitreal injections with anti-vascular endothelial growth factor agents during the ongoing global COVID-19 pandemic. This article provides guidance for ophthalmologists on how to deliver the best possible care for patients while minimizing the risk of infection. METHODS: The Vision Academy's Steering Committee of international retinal disease experts convened to discuss key considerations for managing patients with retinal disease during the COVID-19 pandemic. After reviewing the existing literature on the issue, members put forward recommendations that were systematically refined and voted on to develop this guidance. RESULTS: The considerations focus on the implementation of steps to minimize the exposure of patients and healthcare staff to COVID-19. These include the use of personal protective equipment, adherence to scrupulous hygiene and disinfection protocols, pre-screening to identify symptomatic patients, and reducing the number of people in waiting rooms. Other important measures include triaging of patients to identify those at the greatest risk of irreversible vision loss and prioritization of treatment visits over monitoring visits where possible. In order to limit patient exposure, ophthalmologists should refrain from using treatment regimens that require frequent monitoring. CONCLUSION: Management of patients with retinal disease receiving intravitreal injections during the COVID-19 pandemic will require adjustment to regular clinical practice to minimize the risk of exposure of patients and healthcare staff, and to prioritize those with the greatest medical need. The safety of patients and healthcare staff should be of paramount importance in all decision-making.


Assuntos
Infecções por Coronavirus/prevenção & controle , Injeções Intravítreas , Oftalmologia/organização & administração , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Doenças Retinianas/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Betacoronavirus , Desinfecção , Humanos , Equipamento de Proteção Individual
6.
J Med Chem ; 63(6): 2854-2876, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-32096640

RESUMO

Peroxisome proliferator-activated receptor alpha (PPARα) is expressed in retinal Müller cells, endothelial cells, and in retinal pigment epithelium; agonism of PPARα with genetic or pharmacological tools ameliorates inflammation, vascular leakage, neurodegeneration, and neovascularization associated with retinal diseases in animal models. As such, PPARα is a promising drug target for diabetic retinopathy and age-related macular degeneration. Herein, we report proof-of-concept in vivo efficacy in an streptozotocin-induced vascular leakage model (rat) and preliminary pharmacokinetic assessment of a first-generation lead 4a (A91). Additionally, we present the design, synthesis, and evaluation of second-generation analogues, which led to the discovery of 4u and related compounds that reach cellular potencies <50 nM and exhibit >2,700-fold selectivity for PPARα over other PPAR isoforms. These studies identify a pipeline of candidates positioned for detailed PK/PD and pre-clinical evaluation.


Assuntos
Benzilaminas/química , Benzilaminas/farmacologia , Retinopatia Diabética/tratamento farmacológico , PPAR alfa/agonistas , Animais , Benzilaminas/farmacocinética , Benzilaminas/uso terapêutico , Permeabilidade Capilar/efeitos dos fármacos , Linhagem Celular , Retinopatia Diabética/induzido quimicamente , Retinopatia Diabética/metabolismo , Modelos Animais de Doenças , Desenho de Fármacos , Descoberta de Drogas , Humanos , PPAR alfa/metabolismo , Ratos , Doenças Retinianas/tratamento farmacológico , Doenças Retinianas/metabolismo , Estreptozocina
7.
Invest Ophthalmol Vis Sci ; 61(2): 17, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32053727

RESUMO

Purpose: Vigabatrin (VGB) is an effective antiepileptic that increases concentrations of inhibitory γ-aminobutyric acid (GABA) by inhibiting GABA transaminase. Reports of VGB-associated visual field loss limit its clinical usefulness, and retinal toxicity studies in laboratory animals have yielded conflicting results. Methods: We examined the functional and morphologic effects of VGB in C57BL/6J mice that received either VGB or saline IP from 10 to 18 weeks of age. Retinal structure and function were assessed in vivo by optical coherence tomography (OCT), ERG, and optomotor response. After euthanasia, retinas were processed for immunohistochemistry, and retinal GABA, and VGB quantified by mass spectrometry. Results: No significant differences in visual acuity or total retinal thickness were identified between groups by optomotor response or optical coherence tomography, respectively. After 4 weeks of VGB treatment, ERG b-wave amplitude was enhanced, and amplitudes of oscillatory potentials were reduced. Dramatic rod and cone bipolar and horizontal cell remodeling, with extension of dendrites into the outer nuclear layer, was observed in retinas of VGB-treated mice. VGB treatment resulted in a mean 3.3-fold increase in retinal GABA concentration relative to controls and retinal VGB concentrations that were 20-fold greater than brain. Conclusions: No evidence of significant retinal thinning or ERG a- or b-wave deficits were apparent, although we describe significant alterations in ERG b-wave and oscillatory potentials and in retinal cell morphology in VGB-treated C57BL/6J mice. The dramatic concentration of VGB in retina relative to the target tissue (brain), with a corresponding increase in retinal GABA, offers insight into the pathophysiology of VGB-associated visual field loss.


Assuntos
Anticonvulsivantes/farmacologia , GABAérgicos/farmacologia , Plasticidade Neuronal/efeitos dos fármacos , Retina/efeitos dos fármacos , Vigabatrina/farmacologia , Animais , Masculino , Camundongos Endogâmicos C57BL , Plasticidade Neuronal/fisiologia , Músculos Oculomotores/efeitos dos fármacos , Distribuição Aleatória , Retina/fisiopatologia , Doenças Retinianas/tratamento farmacológico , Doenças Retinianas/fisiopatologia , Tomografia de Coerência Óptica , Campos Visuais/fisiologia
8.
Nat Commun ; 11(1): 694, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019921

RESUMO

Neovascular age-related macular degeneration and diabetic retinopathy are prevalent causes of vision loss requiring frequent intravitreous injections of VEGF-neutralizing proteins, and under-treatment is common and problematic. Here we report incorporation of sunitinib, a tyrosine kinase inhibitor that blocks VEGF receptors, into a non-inflammatory biodegradable polymer to generate sunitinib microparticles specially formulated to self-aggregate into a depot. A single intravitreous injection of sunitinib microparticles potently suppresses choroidal neovascularization in mice for six months and in another model, blocks VEGF-induced leukostasis and retinal nonperfusion, which are associated with diabetic retinopathy progression. After intravitreous injection in rabbits, sunitinib microparticles self-aggregate into a depot that remains localized and maintains therapeutic levels of sunitinib in retinal pigmented epithelium/choroid and retina for more than six months. There is no intraocular inflammation or retinal toxicity. Intravitreous injection of sunitinib microparticles provides a promising approach to achieve sustained suppression of VEGF signaling and improve outcomes in patients with retinal vascular diseases.


Assuntos
Doenças Retinianas/tratamento farmacológico , Sunitinibe/administração & dosagem , Animais , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/genética , Neovascularização de Coroide/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Coelhos , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Doenças Retinianas/genética , Doenças Retinianas/metabolismo , Sunitinibe/química , Sunitinibe/farmacocinética , Suínos , Porco Miniatura , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
Eur J Ophthalmol ; 30(3): NP14-NP17, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-30841747

RESUMO

PURPOSE: To report a case of Purtscher-like retinopathy due to atypical hemolytic uremic syndrome and the changes seen in the optical coherence tomography angiography before and after treatment with eculizumab. CASE DESCRIPTION: A 22-year-old man with an unremarkable medical history presented with acute, bilateral blurred vision and headache of 1-week duration. Best corrected visual acuity of 20/50 and 20/40, respectively, in the patient's right eye and left eye. Funduscopy revealed multiple cotton-wool spots associated with intrarretinal fluid. Swept source optical coherence tomography revealed multifocal retinal detachments with increased choroidal thickness. Optical coherence tomography angiography showed areas of ischemia in both capillary plexus. Due to concurrent symptoms and laboratory analysis, he was diagnosed with atypical hemolytic uremic syndrome and secondary Purtscher-like retinopathy; therefore, treatment with eculizumab was initiated. After 2 months revascularization of the previous ischemic areas was seen in the optical coherence tomography angiography that were correlated with best corrected visual acuity improvement. CONCLUSION: Our findings suggest that evaluation of the macular capillary plexus revascularization by optical coherence tomography angiography during the disease could help to predict an improvement of best corrected visual acuity in these patients and the measurement of choroidal thickness could give us information about the resolution of the pathologic process.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/complicações , Doenças Retinianas/diagnóstico , Doenças Retinianas/etiologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Angiografia por Tomografia Computadorizada , Angiofluoresceinografia/métodos , Seguimentos , Humanos , Masculino , Doenças Retinianas/tratamento farmacológico , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adulto Jovem
10.
Br J Ophthalmol ; 104(1): 39-46, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31040132

RESUMO

PURPOSE: To evaluate the real-life safety profile of intravitreal dexamethasone implant injection for various retinal conditions. METHODS: Retrospective multicenter analysis of intravitreal dexamethasone implant injections (700 µg) due to various retinal conditions including central retinal venous occlusion (1861 injections), diabetic macular oedema (3104 injections), post-surgical cystoid macular oedema (305 injections) and uveitis (381 injections). The eyes were evaluated mainly for the occurrence of adverse events such as glaucoma, cataract, retinal detachment and endophthalmitis along during the follow-up period. RESULTS: A total of 6015 injections in 2736 eyes of 1441 patients (mean age of 65.7±12.9 years) were in total analysed over an average period of 18 months (range 6 months to 102 months). A total of 576 eyes (32.5% of the phakic eyes) developed cataract requiring surgical intervention. However, visually insignificant cataract progression was observed in another 259 phakic eyes (14.6%) which did not require surgical removal. A total of 727 eyes (26.5%) experienced an intraocular pressure (IOP) rise of >25 mm Hg, with 155 eyes (5.67%) having a prior history of glaucoma and 572 eyes (20.9%) having new onset IOP rise. Overall, more than 90% of eyes with IOP rise were managed medically, and 0.5% eyes required filtering surgery. Endophthalmitis (0.07%), retinal detachment (0.03%) and vitreous haemorrhage (0.03%) were rare. There was no significant change in visual acuity (p=0.87) and central macular thickness (p=0.12) at the last follow-up. CONCLUSION: This is the largest real-life study assessing the safety of intravitreal dexamethasone implant injections in various retinal conditions. Cataract progression and intraocular pressure rise are the most common side effects, but are often rather easily manageable.


Assuntos
Dexametasona/efeitos adversos , Glucocorticoides/efeitos adversos , Doenças Retinianas/tratamento farmacológico , Idoso , Catarata/induzido quimicamente , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Progressão da Doença , Implantes de Medicamento , Feminino , Glaucoma/induzido quimicamente , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Oclusão da Veia Retiniana/tratamento farmacológico , Estudos Retrospectivos , Uveíte Posterior/tratamento farmacológico
11.
Mol Vis ; 25: 610-624, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31700226

RESUMO

Bile acids are produced in the liver and excreted into the intestine, where their main function is to participate in lipid digestion. Ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA) have shown antiapoptotic, anti-inflammatory, and antioxidant effects in various models of neurodegenerative diseases. However, little is known about signaling pathways and molecular mechanisms through which these bile acids act as neuroprotectors, delaying translation to the clinical setting. We review evidence supporting a potentially therapeutic role for bile acids in retinal disorders, and the mechanisms and pathways involved in the cytoprotective effects of bile acids from the liver and the enterohepatic circulation to the central nervous system and the retina. As secondary bile acids are generated by the microbiota metabolism, bile acids might be a link between neurodegenerative retinal diseases and microbiota.


Assuntos
Fármacos Neuroprotetores/uso terapêutico , Doenças Retinianas/tratamento farmacológico , Ácido Tauroquenodesoxicólico/uso terapêutico , Ácido Ursodesoxicólico/uso terapêutico , Animais , Citoproteção/efeitos dos fármacos , Humanos , Degeneração Neural/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Ácido Tauroquenodesoxicólico/química , Ácido Tauroquenodesoxicólico/farmacologia , Ácido Ursodesoxicólico/química , Ácido Ursodesoxicólico/farmacologia
12.
Arch. Soc. Esp. Oftalmol ; 94(11): 540-544, nov. 2019. ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-187410

RESUMO

El objetivo fue presentar un caso de retinopatía autoinmune (AIR) no paraneoplásica con anticuerpos antirecoverina positivos. Una mujer de 28 años consultó por pérdida de la agudeza visual bilateral de 8 meses de evolución. El fondo de ojo presentó un patrón de coloración moteado desde el centro a la periferia, sin espículas pigmentarias. La angiografía mostró un patrón de áreas puntiformes, sin fuga de contraste. Se observó una reducción de las capas externas de la retina en la tomografía de coherencia óptica, mientras que el electrorretinograma mostró una ausencia de respuesta de los conos y los bastones en el ojo derecho, y una respuesta disminuida de los conos con ausencia de respuesta de los bastones en el ojo izquierdo. Se sospechó AIR, y se empezó tratamiento empírico con corticoides a la espera de los resultados del Western-blot, que posteriormente resultó positivo para recoverina, GAPDH, anti-alfa-enolasa y aldolasa. Mientras pudo ser tratada, la agudeza visual se mantuvo estable. Al retirarse el tratamiento, esta se redujo a amaurosis en el ojo derecho y movimiento de manos en el ojo izquierdo


The case is presented of a non-paraneoplastic autoimmune retinopathy (AIR) with positive anti-recoverin autoantibodies. A 28-year-old woman presented with a rapidly progressive bilateral visual loss of 8 months onset. Funduscopic examination revealed diffuse fine mottled atrophic changes in both eyes. Fluorescein angiographic studies showed a pattern of mottled areas of early hyperfluorescence without leakage of dye. In the ocular coherence tomography it was observed that was a loss of external layers. The electroretinogram showed absence of rod and cone responses in the right eye, and diminished cone response associated to absence of rod response in the left eye. AIR was suspected, and empirical corticosteroid treatment was started while waiting for Western-blot results, which was finally positive for recoverin, GAPDH, anti-alpha-enolase, and aldolase. The patient was able to be treated, and her visual acuity remained stable, but as soon as it was suspended, vision was completely lost in the right eye and reduced to hand movement in the left eye


Assuntos
Humanos , Feminino , Adulto , Anticorpos/análise , Doenças Autoimunes/imunologia , Recoverina/imunologia , Doenças Retinianas/imunologia , Doenças Autoimunes/diagnóstico por imagem , Doenças Autoimunes/tratamento farmacológico , Eletrorretinografia , Fundo de Olho , Glucocorticoides/uso terapêutico , Ácido Micofenólico/uso terapêutico , Prednisona/uso terapêutico , Doenças Retinianas/diagnóstico por imagem , Doenças Retinianas/tratamento farmacológico , Tomografia de Coerência Óptica , Acuidade Visual , Campos Visuais
13.
PLoS One ; 14(10): e0223944, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31647843

RESUMO

AIM: To evaluate the safety of 1.25mg and 2mg intravitreal ziv-aflibercept (IVZ) in Ghanaian eyes with choroido-retinal vascular diseases. DESIGN: Prospective, randomised, double blind, interventional study. METHODS: Twenty patients with centre involving macular oedema in diabetic retinopathy, retinal vein occlusion, and neovascular age-related macular degeneration were assigned to 2 groups receiving 3 doses of 1.25mg/0.05ml (group 1) and 2mg/0.08ml IVZ (Group 2) at 4 weekly intervals. Safety data was collected after 30 minutes, 1 and 7 days, and 4, 8 and 12 weeks after injection. Changes in continuous variables were compared using paired t-test and categorical variables were compared using chi-square test of proportions. Repeated-Measures ANOVA with nesting test was used to compare variations in continuous variables by IVZ dose over time. Primary outcome measures were ocular and systemic adverse events at 4 weeks. RESULTS: Eleven females and nine males, with mean age of 63.2± 7.3 years were included. Ocular adverse events included subconjunctival haemorrhage in 1 eye, intraocular pressure (IOP) >21mmHg at 30 minutes in 6 eyes and mild pain in 3 eyes at 1-day. There was no significant difference in IOP rise between the 2 groups at 30 minutes (p = 0.21). No other ocular or systemic adverse events were observed. There was significant improvement in the best corrected visual acuity (LogMAR) from 0.95±0.6 to 0.6±0.4 (p<0.01) and 0.47±0.3 (p<0.01), reduction in central subfield foveal thickness from 405.9±140 um at baseline to 255.6±75 um (p<0.01) and 238±88 um (p<0.01) at 4 and 12 weeks respectively, although no difference was observed between the 2 groups (p = 0.34). CONCLUSION: IVZ at 1.25mg and 2mg had similar safety profiles, and did not have any major unexpected adverse events. Further studies with larger cohorts are required to confirm efficacy.


Assuntos
Plexo Corióideo/patologia , Edema Macular/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Doenças Retinianas/tratamento farmacológico , Doenças Vasculares/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Injeções Intravítreas , Edema Macular/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Doenças Retinianas/patologia , Doenças Vasculares/patologia
14.
BMC Ophthalmol ; 19(1): 206, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619195

RESUMO

BACKGROUND: Real-world data (RWD) has been a valuable addition to the scientific literature regarding treatment pathways, clinical outcomes and characteristics of patients with retinal diseases in recent years. Registries, observational studies and patient databases are often used for real-world research. However, there is limited information for each data source on the design, consistency, data captured, limitations and usability for assessing research questions. Using a systematic approach, we identified RWD sources for patients with retinal diseases and assessed them for completeness of data relating to different outcomes. METHODS: A systematic literature review was carried out to identify RWD sources for patients with retinal disease. Potentially relevant articles published between 2006 and 2016 were screened following electronic searches in Embase and MEDLINE. Congress and supplementary searches were undertaken to identify RWD sources that may not be referenced in full publications. For each data source, availability and quantity of data on baseline status, clinical outcomes, treatment and management, safety, and patient-reported and economic burden were assessed using a bespoke completeness assessment tool based on International Consortium for Health Outcomes Measurement guidelines for macular degeneration. Completeness of data for each area of interest in each data source was assessed and rated using a 'good-moderate-poor' rating system based on availability and quantity of available data. Each data source was then given an overall score based on its score for each of the 7 areas of interest. RESULTS: A total of 128 RWD sources from 32 countries were identified. Of the identified sources, 64 sources from 16 countries of interest were analyzed. Most of these sources provided information on baseline status and clinical outcomes and treatment, but few collected data on economic and patient-reported burden. Of the RWD sources analyzed, 10 scored highly in the overall completeness assessment, collecting data on most or all of the areas of interest; these sources are considered to be robust data sources for performing ophthalmology real-world studies. CONCLUSIONS: The study provides a comprehensive list of RWD sources for patients with retinal disease, many of which will be useful for conducting real-world studies in the field of ophthalmology.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Doenças Retinianas/tratamento farmacológico , Acuidade Visual , Humanos , Armazenamento e Recuperação da Informação , Injeções Intravítreas , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
15.
Exp Eye Res ; 189: 107824, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31585119

RESUMO

Injection into the suprachoroidal space (SCS) allows drug delivery targeted to sclera, choroid, and retina. Here, we studied SCS injection formulated with collagenase to expand drug delivery coverage and increase posterior drug targeting within SCS by breaking down collagen fibrils that link sclera and choroid in the SCS. When 1 µm latex microparticles were injected with a collagenase formulation using microneedles into the SCS of rabbit eyes ex vivo and incubated at 37 °C for 4 h, microparticle delivery coverage increased from 20% to 45% and enhanced posterior drug targeting. Collagenase concentration was optimized to 0.5 mg/mL to maximize expanded posterior delivery and minimize tissue damage. Effects of collagenase injection within SCS increased and then plateaued 4 h after injection. Simultaneous injection of collagenase and microparticles had a greater effect on expanded delivery in the SCS compared to sequential injection. Collagenase injection into the SCS of rabbit eyes in vivo was also effective to expand delivery and was generally well-tolerated, showing transiently lowered IOP, but no apparent lasting adverse effects on ocular tissues such as sclera, choroid, and retina, as determined by analyzing histology, sclera tensile strength, and fundus imaging. We conclude that addition of collagenase during SCS injection can expand drug delivery coverage and increase posterior drug targeting.


Assuntos
Colágeno/metabolismo , Colagenases/administração & dosagem , Segmento Posterior do Olho/efeitos dos fármacos , Retina/metabolismo , Doenças Retinianas/tratamento farmacológico , Animais , Corioide , Colagenases/farmacocinética , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Injeções Intraoculares , Pressão Intraocular/fisiologia , Segmento Posterior do Olho/diagnóstico por imagem , Coelhos , Retina/patologia , Doenças Retinianas/metabolismo , Doenças Retinianas/patologia
16.
Arch Soc Esp Oftalmol ; 94(11): 540-544, 2019 Nov.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31470998

RESUMO

The case is presented of a non-paraneoplastic autoimmune retinopathy (AIR) with positive anti-recoverin autoantibodies. A 28-year-old woman presented with a rapidly progressive bilateral visual loss of 8 months onset. Funduscopic examination revealed diffuse fine mottled atrophic changes in both eyes. Fluorescein angiographic studies showed a pattern of mottled areas of early hyperfluorescence without leakage of dye. In the ocular coherence tomography it was observed that was a loss of external layers. The electroretinogram showed absence of rod and cone responses in the right eye, and diminished cone response associated to absence of rod response in the left eye. AIR was suspected, and empirical corticosteroid treatment was started while waiting for Western-blot results, which was finally positive for recoverin, GAPDH, anti-alpha-enolase, and aldolase. The patient was able to be treated, and her visual acuity remained stable, but as soon as it was suspended, vision was completely lost in the right eye and reduced to hand movement in the left eye.


Assuntos
Anticorpos/análise , Doenças Autoimunes/imunologia , Recoverina/imunologia , Doenças Retinianas/imunologia , Adulto , Doenças Autoimunes/diagnóstico por imagem , Doenças Autoimunes/tratamento farmacológico , Eletrorretinografia , Feminino , Fundo de Olho , Glucocorticoides/uso terapêutico , Humanos , Ácido Micofenólico/uso terapêutico , Prednisona/uso terapêutico , Doenças Retinianas/diagnóstico por imagem , Doenças Retinianas/tratamento farmacológico , Tomografia de Coerência Óptica , Acuidade Visual , Campos Visuais
17.
Arq Bras Oftalmol ; 82(5): 432-435, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31482963

RESUMO

A 27-year-old man presented with a complaint of decreased visual acuity in the right eye. Best-corrected visual acuity was 20/60 in the right eye and 20/20 in the left eye. Right eye fundoscopy revealed mild vitritis, multifocal yellowish lesions, and macular serous retinal detachment. Left eye evaluation was normal. Acute posterior multifocal placoid pigment epitheliopathy was diagnosed in the right eye. Complementary exams revealed a strong reaction to the Mycobacterium tuberculosis purified protein derivative test, thus treatment for tuberculosis was initiated. Baseline fluorescein angiography of the right eye revealed early hypofluorescence and late staining of the lesions. Optical coherence tomography of the right eye demonstrated the accumulation of subretinal and intraretinal fluid associated with cystoid macular edema. During follow-up, the retinal fluid and cysts disappeared, which was followed by disorganization of foveal interdigitation and ellipsoid zones. This is the second described case of unilateral acute posterior multifocal placoid pigment epitheliopathy in a patient with a strong positive result to the M. tuberculosis purified protein derivative test.


Assuntos
Epitélio Pigmentado Ocular/diagnóstico por imagem , Doenças Retinianas/diagnóstico , Tuberculose Ocular/diagnóstico , Doença Aguda , Adulto , Anti-Inflamatórios/uso terapêutico , Antibióticos Antituberculose/uso terapêutico , Angiofluoresceinografia , Humanos , Masculino , Prednisona/uso terapêutico , Doenças Retinianas/tratamento farmacológico , Tomografia de Coerência Óptica , Tuberculose Ocular/tratamento farmacológico , Acuidade Visual
18.
BMC Public Health ; 19(1): 1252, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31510981

RESUMO

BACKGROUND: Antiangiogenic therapy has proved to be an important therapeutic tool for many retinal vascular diseases; however, its availability is limited in developing countries. This study sought to describe the bevacizumab vial sharing process and to evaluate the impact of this repackaging system on the costs incurred in a Brazilian public hospital. METHOD: This retrospective study compared the number and costs of intravitreal antiangiogenic injections approved via court order in the first year of the study (2015) to the number and costs of the bevacizumab injections provided through the use of vial sharing in the second year of the study (2016). Vial sharing consists of the traditional process used to repackage bevacizumab; in this case, however, the drug samples used were the residual volume from the preparation of bevacizumab for oncology patients. The hospital adhered to the guidelines established by the Brazilian Health Surveillance Agency (ANVISA). RESULTS: In the first year of the study and using medication obtained through court orders, 550 intravitreal injections were performed in the ophthalmology ambulatory care center. Based on local pricing tables, the total cost of the medication was BRL$1,036,056.25 (USD$267,546.58), and the average cost of each application was BRL$1883.74 (USD$486.45). In the second year of the study, 1081 intravitreal applications were performed at the same hospital using doses obtained through bevacizumab vial sharing. The total cost was BRL$21,942.49 (USD$5663.30) and the per-unit cost was BRL$20.30, or USD$5.23 (a savings of 97.88%). CONCLUSION: This study found that bevacizumab vial sharing led to a significant reduction in public health care costs associated with antiangiogenic treatment and increased the availability of the drug to public health care patients. These results can be extrapolated to other types of drugs and health care systems.


Assuntos
Inibidores da Angiogênese/economia , Bevacizumab/economia , Custos de Medicamentos , Doenças Retinianas/tratamento farmacológico , Doenças Retinianas/economia , Idoso , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Brasil , Análise Custo-Benefício , Feminino , Custos de Cuidados de Saúde , Humanos , Injeções Intravítreas/economia , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
Cells ; 8(8)2019 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-31426601

RESUMO

Dysregulation of vascular networks is characteristic of eye diseases associated with retinal cell degeneration and visual loss. Visual impairment is also the consequence of photoreceptor degeneration in inherited eye diseases with a major inflammatory component, but without angiogenic profile. Among the pathways with high impact on vascular/degenerative diseases of the eye, a central role is played by a system formed by the ligand urokinase-type plasminogen activator (uPA) and its receptor uPAR. The uPAR system, although extensively investigated in tumors, still remains a key issue in vascular diseases of the eye and even less studied in inherited retinal pathologies such as retinitis pigmantosa (RP). Its spectrum of action has been extended far beyond a classical pro-angiogenic function and has emerged as a central actor in inflammation. Preclinical studies in more prevalent eye diseases characterized by neovascular formation, as in retinopathy of prematurity, wet macular degeneration and rubeosis iridis or vasopermeability excess as in diabetic retinopathy, suggest a critical role of increased uPAR signaling indicating the potentiality of its modulation to counteract neovessel formation and microvascular dysfunction. The additional observation that the uPAR system plays a major role in RP by limiting the inflammatory cascade triggered by rod degeneration rises further questions about its role in the diseased eye.


Assuntos
Inflamação/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Doenças Retinianas , Ativador de Plasminogênio Tipo Uroquinase , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Sprague-Dawley , Receptores de Ativador de Plasminogênio Tipo Uroquinase/antagonistas & inibidores , Receptores de Ativador de Plasminogênio Tipo Uroquinase/fisiologia , Doenças Retinianas/tratamento farmacológico , Doenças Retinianas/metabolismo , Doenças Retinianas/patologia , Ativador de Plasminogênio Tipo Uroquinase/antagonistas & inibidores , Ativador de Plasminogênio Tipo Uroquinase/fisiologia
20.
Jpn J Ophthalmol ; 63(5): 396-401, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31446502

RESUMO

PURPOSE: In our previous report, intravitreal injection using 0.25% povidone-iodine to irrigate the conjunctival sac together with pre- and post-injection topical antibiotics achieved an incidence of post-injection endophthalmitis significantly lower than other reports. In this study, we examined whether similarly low incidence is achieved without using any topical antibiotics. STUDY DESIGN: Prospective cohort study. METHODS: We evaluated intravitreal injections of anti-vascular endothelial growth factor agents conducted by vitreoretinal specialists at the outpatient injection room of a single university hospital. This study had two protocols. First stage: We performed more than 3000 injections with pre-injection but without post-injection topical antibiotics. Final stage: After confirming no case of endophthalmitis in the first stage, we performed more than 12,500 injections without either pre- or post-injection topical antibiotics. In both protocols, we used 0.25% povidone-iodine to sterilize the conjunctival sac both before and after injection. RESULTS: First stage was performed between April 2015 and January 2016. No case of suspected or proven infectious endophthalmitis occurred in 6039 injections [95% confidence interval (CI) 0-0.000497%]. Final stage was performed between February 2016 and November 2017. No case of suspected or proven infectious endophthalmitis occurred in 12,523 injections (95% CI 0-0.00024%). This result was comparable to our previous study using both pre- and post-injection topical antibiotics (0/15,144 injections, 95% CI 0-0.000198%). CONCLUSION: Using conjunctival sac irrigation with 0.25% povidone-iodine before and after intravitreal injection, the incidence of endophthalmitis remains low even when the use of pre- or post-injection topical antibiotics is discontinued.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Endoftalmite/epidemiologia , Infecções Oculares Bacterianas/epidemiologia , Administração Tópica , Antibacterianos/administração & dosagem , Endoftalmite/etiologia , Infecções Oculares Bacterianas/etiologia , Seguimentos , Humanos , Incidência , Injeções Intravítreas/efeitos adversos , Japão/epidemiologia , Estudos Prospectivos , Doenças Retinianas/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
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