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1.
Invest Ophthalmol Vis Sci ; 61(1): 2, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31995152

RESUMO

Purpose: To determine the impact of topographic locations on the progression rate of geographic atrophy (GA). Methods: We searched in five literature databases up to May 3, 2019, for studies that evaluated the growth rates of GA lesions at different retinal regions. We performed random-effects meta-analyses to determine and compare the GA effective radius growth rates in four location groups defined by two separate classification schemes: (1) macular center point involved (CPI) or spared (CPS) in classification 1, and (2) foveal zone involved (FZI) or spared (FZS) in classification 2. We then estimated the GA growth rate in eight topographic zones and used the data to model the GA expansion. Results: We included 11 studies with 3254 unique eyes. In studies that used classification 1, the effective radius growth rate was 30.1% higher in the CPS group (0.203 ± 0.013 mm/year) than in the CPI group (0.156 ± 0.011 mm/year) (P < 0.001). This trend became significantly more prominent in classification 2, where the growth rate was 61.7% higher in the FZS group (0.215 ± 0.012 mm/year) than in the FZI group (0.133 ± 0.009 mm/year) (P < 0.001). The estimated GA effective radius growth rates in eight retinal zones fit a Gaussian function, and the modeling of GA expansion gave rise to various GA configurations comparable to clinical observations. Conclusions: This study indicates that the GA progression rate varies significantly across different retinal locations. Our analysis may shed light on the natural history and underlying mechanism of GA progression.


Assuntos
Atrofia Geográfica/diagnóstico , Retina/patologia , Bases de Dados Factuais , Progressão da Doença , Exsudatos e Transudatos , Atrofia Geográfica/fisiopatologia , Humanos , Degeneração Macular/diagnóstico
3.
Lakartidningen ; 1162019 Dec 02.
Artigo em Sueco | MEDLINE | ID: mdl-31794048

RESUMO

This study reviewed 102 decisions on error reports in ophthalmic health care in Sweden between March 2017 and October 2018. The study included children, adults, women and men. We found that there was a clear association between long waiting times for ophthalmic health care and negative visual outcomes. As a result of care delay, 71 percent of the patients had moderate vision loss and 17 percent of the patients experienced severe vision loss. Patients with glaucoma and wet macular degeneration accounted for the majority of the patients with negative outcomes. Timely follow-up and prompt treatment are critical to patients' visual outcomes.


Assuntos
Erros Médicos/estatística & dados numéricos , Oftalmologia/normas , Tempo para o Tratamento , Adulto , Idoso , Criança , Feminino , Glaucoma/epidemiologia , Humanos , Degeneração Macular/epidemiologia , Masculino , Pessoa de Meia-Idade , Qualidade da Assistência à Saúde/normas , Suécia/epidemiologia , Resultado do Tratamento , Transtornos da Visão/epidemiologia , Listas de Espera
4.
Adv Gerontol ; 32(4): 599-601, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31800189

RESUMO

The article compares the course of age-related macular degeneration in elderly patients in three groups after complex therapy (intravitreal administration of angiogenesis blockers and photodynamic therapy). 339 case histories of persons with an average age of 75,6±9,7 years were analyzed (p<0,05). A slight decrease in the area of pathological autofluorescence and retinal thickness according to optical coherence tomography was revealed in all three groups of increased visual acuity. The best effect of combination therapy was observed in the first six months, no further positive dynamics was observed. Thus, timely diagnosis and complex therapy slows down and sometimes stops the progression of age-related macular degeneration and vision loss.


Assuntos
Inibidores da Angiogênese , Degeneração Macular , Retina , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/farmacologia , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Fotoquimioterapia , Retina/efeitos dos fármacos , Retina/patologia , Estudos Retrospectivos , Resultado do Tratamento
5.
Adv Exp Med Biol ; 1185: 3-7, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31884580

RESUMO

Genetic variants of high-temperature requirement A serine peptidase 1 (HTRA1) and age-related maculopathy susceptibility 2 (ARMS2) are associated with age-related macular degeneration (AMD). One HTRA1 single nucleotide polymorphism (SNP) is situated in the promotor region (rs11200638) resulting in increased expression, while two synonymous SNPs are located in exon 1 (rs1049331:C > T, rs2293870:G > T). HtrA1 is known to inhibit transforming growth factor-ß (TGF-ß) signaling, a pathway regulating quiescence of microglia, the resident immune cells of the brain and retina. Microglia-mediated immune responses contribute to AMD pathogenesis. It is currently unclear whether AMD-associated HTRA1 variants influence TGF-ß signaling and microglia phenotypes. Here, we show that an HtrA1 isoform carrying AMD-associated SNPs in exon 1 exhibits increased proteolytic activity. However, when incubating TGF-ß-treated reactive microglia with HtrA1 protein variants, neither the wildtype nor the SNP-associated isoforms changed microglia activation in vitro.


Assuntos
Serina Peptidase 1 de Requerimento de Alta Temperatura A/genética , Degeneração Macular/genética , Microglia/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Serina Endopeptidases
6.
Adv Exp Med Biol ; 1185: 9-13, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31884581

RESUMO

Age-related macular degeneration (AMD) continues to be the leading cause of visual impairment for the elderly in developed countries. It is a complex, multifactorial, progressive disease with diverse molecular pathways regulating its pathogenesis. One of the cardinal features of the early clinical subtype of AMD is the accumulation of lipid- and protein-rich deposits within Bruch's membrane, called drusen, which can be visualized by fundus imaging. Currently, multiple in vitro and in vivo model systems exist, which can be used to help tease out mechanisms associated with different molecular pathways driving disease initiation and progression. Given the lack of treatments for patients suffering from the dry form of AMD, it is imperative to appreciate the different known morphological endpoints associated with the various pathogenic pathways, in order to derive further insights, for the ultimate purpose of disease modeling and development of effective therapeutic interventions.


Assuntos
Lâmina Basilar da Corioide/patologia , Degeneração Macular/patologia , Retina/patologia , Idoso , Humanos
7.
Adv Exp Med Biol ; 1185: 15-19, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31884582

RESUMO

Age-related macular degeneration (AMD) is the most common cause of irreversible blindness. We do not know the cause of the disease and have inadequate prevention and treatment strategies for those at risk or affected. The greatest risk factors include age and race, with the white population at the highest risk for the disease. We developed the hypothesis that pigmentation in the retinal pigment epithelium (RPE) protects darkly pigmented individuals from AMD. We have tested this hypothesis in multiple ways including dissecting the pigmentation pathway in RPE using albinism-related tools, identification of a G protein-coupled receptor in the pigmentation pathway that drives expression of trophic factors, and using a very large retrospective chart analysis to test whether the ligand for the receptor prevents AMD. In total, our results indicate that pigmentation of the RPE is a cornerstone of RPE-retinal interaction and support and that the receptor in the pigmentation pathway most likely underlies the racial bias of the disease. The ligand for that receptor is an ideal candidate as a preventative and treatment for AMD. Here we summarize these results, discussing the research in its entirety with one overall goal, treatment or prevention of AMD.


Assuntos
Proteínas do Olho/metabolismo , Degeneração Macular/fisiopatologia , Glicoproteínas de Membrana/metabolismo , Degeneração Retiniana/fisiopatologia , Epitélio Pigmentado da Retina/fisiologia , Transdução de Sinais , Humanos , Estudos Retrospectivos , Fatores de Risco
8.
Adv Exp Med Biol ; 1185: 21-25, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31884583

RESUMO

The retinal pigmented epithelium (RPE) forms the outer blood-retinal barrier, provides nutrients, recycles visual pigment, and removes spent discs from the photoreceptors, among many other functions. Because of these critical roles in visual homeostasis, the RPE is a principal location of disease-associated changes in age-related macular degeneration (AMD), emphasizing its importance for study in both visual health and disease. Unfortunately, there are no early indicators of AMD or disease progression, a void that could be filled by the development of early AMD biomarkers. Exosomes are lipid bilayer membrane vesicles of nanoscale sizes that are released in a controlled fashion by cells and carry out a number of extra- and intercellular activities. In the RPE they are released from both the apical and basal sides, and each source has a unique signature/content. Exosomes released from the basolateral side of RPE cells enter the systemic circulation via the choroid and thus represent a potential source of retinal disease biomarkers in blood. Here we discuss the potential of targeted immunocapture of eye-derived exosomes and other small extracellular vesicles from blood for eye disease biomarker discovery.


Assuntos
Biomarcadores/sangue , Exossomos/metabolismo , Retina/citologia , Epitélio Pigmentado da Retina/metabolismo , Corioide , Humanos , Degeneração Macular/patologia
9.
Adv Exp Med Biol ; 1185: 27-31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31884584

RESUMO

Prevalence of age-related macular degeneration (AMD), the leading cause of blindness in the United States, increases greatly with age. While age is the greatest risk factor of AMD, other risks such as smoking, family history, complement pathway activation, and race exist. Various systemic inflammatory diseases share many of these risk factors with AMD, as well as a similar inflammatory profile. Due to these similarities, patient database studies analyzing the association between patients with various systemic diseases and AMD have been performed. In this review we will summarize recent finding on this subject and discuss the implications on AMD diagnosis. By gaining greater insight into the association between chronic systemic inflammation and AMD, implications for novel therapeutic approaches to treat AMD pathology may be identified.


Assuntos
Inflamação/complicações , Degeneração Macular/complicações , Comorbidade , Humanos , Prevalência , Fatores de Risco
10.
Adv Exp Med Biol ; 1185: 39-43, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31884586

RESUMO

Age-related macular degeneration (AMD) is one of the leading causes of blindness worldwide. Long-chain and very long-chain polyunsaturated fatty acids (LC and VLC-PUFAs) have been linked to AMD pathogenesis through epidemiologic, biochemical, and genetic studies; however, the exact mechanisms of pathogenesis are unknown. Here, we review the scientific and clinical evidence supporting the role of PUFAs in AMD and discuss future directions for elucidating the roles of these fatty acids in AMD pathogenesis.


Assuntos
Ácidos Graxos Insaturados/metabolismo , Degeneração Macular/patologia , Humanos
11.
Adv Exp Med Biol ; 1185: 45-49, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31884587

RESUMO

The association between age-related macular degeneration (AMD) and biological rhythms has been insufficiently studied; however there are several reasons to believe that impairment in circadian rhythm may affect incidence and pathogenesis of AMD. The current understanding of AMD pathology is based on age-related, cumulative oxidative damage to the retinal pigmented epithelium (RPE) partially due to impaired clearance of phagocytosed photoreceptor outer segments. In higher vertebrates, phagocytosis of the outer segments is synchronized by circadian rhythms and occurs shortly after dawn, followed by lysosomal-mediated clearance. Aging has been shown to be associated with the changes in circadian rhythmicity of melatonin production, which can be a major factor contributing to the impaired balance between phagocytosis and clearance and increased levels of reactive oxygen species resulting in degenerative changes in the retina. This minireview summarizes studies linking AMD with melatonin production and discusses challenges and perspectives of this area of research.


Assuntos
Ritmo Circadiano , Degeneração Macular/patologia , Melatonina/biossíntese , Epitélio Pigmentado da Retina/patologia , Animais , Humanos , Fagocitose , Espécies Reativas de Oxigênio
12.
Adv Exp Med Biol ; 1185: 51-55, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31884588

RESUMO

The importance of cholesterol as a structural component of photoreceptors and the association between impaired cholesterol homeostasis and age-related macular degeneration (AMD) prompted in the last years a deep investigation of its metabolism in the retina. Here, we focus on the export of cholesterol from intracellular membranes to extracellular acceptors, an active mechanism mediated by the ATP-binding cassette transporters A1 and G1 (ABCA1 and G1) also known as "active cholesterol efflux." Expression of genes involved in this pathway was shown for most retinal cells, while functional in vitro assays focused on the retinal pigment epithelium (RPE) due to availability of cell models. Cell-specific knockout (KO) mice were generated in the past years, and their characterization unveils an important role of the ABCA1/G1 pathway in RPE, rods, and retinal inflammatory cells. The actual involvement of cholesterol efflux in the pathogenesis of AMD still needs to be demonstrated and will help in establishing the scientific rationale for targeting the ABCA1/G1 pathway in retinal diseases.


Assuntos
Colesterol/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Transporte Biológico , Degeneração Macular/metabolismo , Camundongos , Camundongos Knockout
13.
Adv Exp Med Biol ; 1185: 413-417, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31884647

RESUMO

The retina is one of the tissues with the highest metabolic activity in the body, and the energy-demanding photoreceptors require appropriate oxygen levels for photo- and neurotransduction. Accumulating evidence suggests that age-related changes in the retina may reduce oxygen supply to the photoreceptors and trigger a chronic hypoxic response. A detailed understanding of the molecular response to hypoxia is crucial, as hindered oxygen delivery may contribute to the development and progression of retinal pathologies such as age-related macular degeneration (AMD). Important factors in the cellular response to hypoxia are microRNAs (miRNAs), which are small, noncoding RNAs that posttranscriptionally regulate gene expression by binding to mRNA transcripts. Here, we discuss the potential role of hypoxia-regulated miRNAs in connection to retinal pathologies.


Assuntos
Hipóxia/patologia , MicroRNAs/genética , Oxigênio/fisiologia , Retina/patologia , Envelhecimento , Humanos , Degeneração Macular/patologia , Doenças Retinianas/patologia
14.
Cesk Slov Oftalmol ; 75(3): 130-135, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31779461

RESUMO

PURPOSE: To present pilot results of the project in which the primary goal is to optimize way how to increase the quality of life of patients with the stable maculopathy by implanting intraocular Scharioth macular lens (SML) and modulating visual plasticity by a transcranial electrical stimulation (tES) together with a visual rehabilitation. MATERIALS AND METHODS: The study will include 20 patients with stable maculopathy (mainly age-related macular degeneration - AMD) who underwent cataract surgery in past and are eligible for SML implantation. The duration of the project is 3 years. During the first year of the project 17 patients were screened, SML implantation was recommended to 4 of them. They met the indication criteria of SML implantation and SML was implanted into the better seeing eye. The third postoperative day, the tES sessions started and were applied 20 times in the first month after SML implantation. The stimulation was delivered in double blind design (a stimulated and a shame group). Visual exercises and rehabilitation took place during the tES. The patients were examined ophthalmologically and also using electrophysiological methods. RESULTS: Before the implantation, the best corrected distance visual acuity was 0.23. At near it was Jaeger number 15 uncorrected, with +3.0 sphere dioptres J.No.10.5 and with +6.0 sph dpt J.No. 4.5. After the surgery and visual rehabilitation BCVA was 0.13 after 3 weeks, 0.2 after 2 months and 0.14 after 6 months. At near it was uncorrected J.No.7.5 after 3 weeks, J.No.7 after 2 months and J.No.5 after 6 months. CONCLUSION: According to a few participants, the impact of SML implantation together with intensive visual rehabilitation on vision at near and on satisfaction of patients with AMD could not be significantly established. Nevertherless, these patients are limited in their daily activities and SML is one of the solutions for them. The project is ongoing and blinded still, there is also a need of more participants to assess the effect of tES on vision, the results will be presented. We have proven the safety of methods used in the project.


Assuntos
Terapia por Estimulação Elétrica , Lentes Intraoculares , Degeneração Macular , Facoemulsificação , Método Duplo-Cego , Humanos , Implante de Lente Intraocular , Degeneração Macular/terapia , Qualidade de Vida , Acuidade Visual
15.
J Biomed Nanotechnol ; 15(12): 2305-2320, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31748013

RESUMO

Verteporfin photodynamic therapy (PDT) has been approved for the treatment of exudative age-related macular degeneration (AMD) for over a decade. However, its extensive application has been impeded by inevitably collateral tissue damage and immediate induction of angiogenesis, in addition to the need of multiple treatments. In order to develop prospective photosensitizers for clinical use, a triphenyl phosphonium-modified cationic liposomal hypocrellin B (TPP cationic LHB) for angiogenic targeting and endothelial internalization was constructed. With optimal PDT parameters, TPP cationic LHB can lead to death of choroid-retinal vascular endothelial cells while cause negligible damage to collateral retinal pigment epithelium cells. This is likely due to the mitochondria targeting and effective intracellular singlet oxygen generation of TPP cationic LHB in vascular endothelial cells. Additionally, in vivo chick chorioallantoic membrane assay indicated the elevated neovessel-targeting ability and photo-induced anti-angiogenic activity of TPP cationic LHB. Furthermore, TPP cationic LHB PDT is able to maintain neovessel occlusion for an extended period of time compared with verteporfin PDT, without inducing significant increased expression of some angiogenic factors, such as vascular endothelial growth factor and integrin αvß3. This study describes a facile strategy that may be useful for developing new-generation photosensitizers to circumvent the limitations of PDT treatment of exudative AMD.


Assuntos
Degeneração Macular , Perileno/análogos & derivados , Fotoquimioterapia , Quinonas/uso terapêutico , Animais , Neovascularização de Coroide , Células Endoteliais , Lipossomos , Degeneração Macular/tratamento farmacológico , Perileno/uso terapêutico , Fármacos Fotossensibilizantes , Estudos Prospectivos , Fator A de Crescimento do Endotélio Vascular
17.
Klin Monbl Augenheilkd ; 236(12): 1418-1422, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31671463

RESUMO

Age-related macular degeneration (AMD) is the leading cause of blindness in the western world. Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is an effective therapy of the neovascular form of this condition. Multimodal imaging and standardised electronic patient documentation have helped to improve the diagnosis and management of AMD patients recent years. With the advent of artificial intelligence and big data, there are many opportunities for the future. This article is intended to give an overview of possible applications.


Assuntos
Inteligência Artificial , Big Data , Neovascularização de Coroide , Degeneração Macular , Inibidores da Angiogênese , Humanos , Injeções Intravítreas , Degeneração Macular/terapia , Ranibizumab , Fator A de Crescimento do Endotélio Vascular
18.
Vestn Oftalmol ; 135(5. Vyp. 2): 177-183, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31691657

RESUMO

PURPOSE: To study the effect of ranibizumab and aflibercept on the thickness of retinal nerve fiber layer (RNFL) in patients with neovascular age-related macular degeneration (nAMD) and primary open-angle glaucoma (POAG). MATERIAL AND METHODS: The study included 62 patients (62 eyes) with nAMD and comorbid POAG. Patients were divided into two groups depending on the anti-VEGF treatment. The first group included 42 patients (42 eyes) who received injections of ranibizumab. The second group consisted of 20 patients (20 eyes) who received aflibercept. All patients received three injections of ranibizumab or aflibercept with one-month intervals. In addition to standard ophthalmic examination, patients underwent optical coherence tomography of the macular area and peripapillary RNFL. RESULTS: After anti-VEGF treatment, patients of both groups exhibited improvements expressed in reduced macular edema, increased visual acuity and absence of intraocular pressure (IOP) changes, as well as no statistically significant changes in the width and depth of excavation. There was a statistically significant decrease of peripapillary RNFL thickness in the temporal quadrant after treatment. CONCLUSION: The decrease of peripapillary RNFL thickness in the temporal quadrant occurs due to resorption of macular edema. In the absence of statistically significant changes in IOP, width and depth of excavation, intravitreal injections of ranibizumab and aflibercept can be considered safe treatment options for patients with concomitant nAMD and POAG.


Assuntos
Glaucoma , Degeneração Macular , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Inibidores da Angiogênese , Seguimentos , Glaucoma/tratamento farmacológico , Humanos , Injeções Intravítreas , Fibras Nervosas , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento
19.
Vestn Oftalmol ; 135(5): 38-45, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31714511

RESUMO

PURPOSE: To assess the effect of intravitreal administration of anti-VEGF drugs ranibizumab and aflibercept on the functional state of the visual pathway in patients with neovascular age-related macular degeneration (nAMD) and primary open-angle glaucoma (POAG) using the method of recording visual evoked potentials (VEP). MATERIAL AND METHODS: A total of 54 patients (54 eyes) with nAMD and POAG were examined. The control group consisted of 39 healthy patients (39 eyes). The study included 24 patients (24 eyes) with stage IA POAG, 23 patients (23 eyes) with stage IIA POAG, 7 patients (7 eyes) with stage IIIA POAG. All patients with nAMD and POAG were given intravitreal injection of anti-VEGF drug: 35 patients received ranibizumab, 19 patients received aflibercept. Injections were performed monthly for 3 months. Ophthalmologic examination included visometry, biomicroscopy, retinal OCT using SPECTRALIS tomograph ('Heidelberg Engineering GmbH', Germany). VEP were recorded on EP-1000 Multifocal ('Tomey', Germany). All ophthalmologic studies were performed prior to administration of the anti-VEGF preparation and after the 3rd injection. RESULTS: After the third intravitreal injection of anti-VEGF drugs, best corrected visual acuity (BCVA) increased to 0.46±0.1 (p=0.001). According to OCT, central retinal thickness decreased by an average of 110.6 µm, the total volume of the retina decreased by 1.3 mm3, total thickness RNFL - by 3.8 µm (p<0.05). A decrease in the peak latency and an increase in the amplitude of the component P100 of VEP were noted. Statistically significant differences in indicators of VEP between antiangiogenic drugs ranibizumab and aflibercept were not detected (p>0.05). CONCLUSION: Intravitreal administration of anti-VEGF drugs ranibizumab and aflibercept has no negative influence on the functional state of the visual pathway in patients with nAMD and POAG. Intravitreal injections of ranibizumab and aflibercept can be considered a safe treatment option for patients with nAMD and POAG.


Assuntos
Glaucoma , Degeneração Macular , Vias Visuais , Inibidores da Angiogênese , Potenciais Evocados Visuais , Seguimentos , Glaucoma/complicações , Humanos , Injeções Intravítreas , Degeneração Macular/complicações , Ranibizumab , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual
20.
Vestn Oftalmol ; 135(5): 70-74, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31714515

RESUMO

Differential diagnostics of age-related macular degeneration and choroidal tumor is a challenging task for ophthalmologists. Difficulties arise on various stages during establishing the diagnosis: when interpreting ophthalmoscopic picture, or when evaluating the results of visualization methods. The article describes a clinical case of differential diagnostics of age-related macular degeneration and choroidal tumor. The difficulties emerged when interpreting results of ultrasound examination. Optical coherence tomography helped exclude choroidal tumor.


Assuntos
Neoplasias da Coroide , Neovascularização de Coroide , Degeneração Macular , Corioide , Diagnóstico Diferencial , Angiofluoresceinografia , Humanos , Tomografia de Coerência Óptica
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