Ranibizumab e bevacizumab intravítreo no tratamento da neovascularização de coróide extrafoveal da degeneração macular relacionada à idade

PURPOSE: To investigate the efficacy of vascular endothelial growth factor-specific (VEGF) monoclonal antibodies in the treatment of choroidal neovascularization secondary to age-related macular degeneration (AMD) that does not extend beneath the foveal center (nonsubfoveal CNV). METHODS: The study design was a retrospective chart review of consecutive patients over a two-month period under active treatment with bevacizumab and/or ranibizumab for neovascular AMD. Patients with neovascularization within the macula that did not extend beneath the center of the foveal avascular zone, along with at least one large drusen (>125 µ) or many intermediate size (63-124 µ) drusen were included. Best corrected Snellen visual acuity and optical coherence tomography (OCT) analysis of the central macular thickness was recorded for each visit. Serial injections of bevacizumab and/or ranibizumab were administered until there was resolution of subretinal fluid clinically or by OCT. Data over the entire follow-up period were analyzed for overall visual acuity and OCT changes. All patients had follow-up since diagnosis of at least 6 months (mean=9.6 months). RESULTS: Of the thirteen included patients, eleven had reduction of retinal thickening in the area involved by the CNV. The remaining two patients did not have OCT data available but had no fluid or activity on clinical examination at last follow-up. One patient (8%) lost one line of vision; one (8%) remained stable, and eleven (84%) gained one or more lines of visual acuity. Three patients (23%) gained three or more lines. The average treatment outcome for all patients was a gain of 1.7 ± 1.3 lines of Snellen acuity. Both therapeutic agents were effective, with an average gain of 1.6 ± 0.6 lines for patients treated with bevacizumab, 1.5 ± 1.9 lines gained for patients treated with ranibizumab and 2.5 ± 0.7 lines gained in the two patients who received both agents over the course of their treatment. CONCLUSIONS: The use of intravitreal anti-VEGF agents for nonsubfoveal CNV in AMD is effective. Our results are comparable to published results from large-scale trials of anti-VEGF therapy for subfoveal CNV. Our data support the idea that bevacizumab or ranibizumab appear to be the treatment of choice for AMD patients with nonsubfoveal CNV.OBJETIVO: Investigar a eficácia dos anti-angiogênicos ranibizumab e bevacizumab injetados intravítreo, no tratamento de pacientes com neovascularização de coróide extrafoveal em degeneração macular relacionada à idade. MÉTODOS: Foram avaliados 13 pacientes com neovascularização de coróide extrafoveal em degeneração macular relacionada à idade do Setor de Retina e Vítreo do Departamento de Oftalmologia da Universidade de Iowa, Estados Unidos, que foram tratados por meio de injeção vítrea de ranibizumab e bevacizumab separadamente, em um período de dois anos. Após as injeções iniciais os pacientes foram acompanhados por exames de OCT e as injeções foram repetidas com 4 a 8 semanas dependendo da presença de líquido sub-retiniano e macular. RESULTADOS: Doze pacientes tiveram ganhos de linhas de visão se comparados com a visão antes do tratamento. Onze pacientes tiveram redução do espessamento retiniano na área envolvida pelo CNV e diminuição e resolução do espessamento macular na sua visita final de avaliação. Um paciente (8%) perdeu uma linha de visão se comparado à visão prévia ao tratamento. Pacientes tratados com o ranibizumab tiveram em média 2,5 ± 0,7 ganhos de linhas de visão. Pacientes tratados com bevacizumab tiveram em média 1,6 ± ganhos de linhas de visão. CONCLUSÃO: No tratamento de pacientes com a neovascularização de coróide extrafoveal em degeneração macular relacionada à idade, a injeção vítrea de ranibizumab ou bevacizumab é efetiva e pode ser a opção de escolha.University of Iowa Department of Ophthalmology Hospitals and ClinicsFederal University of São Paulo Department of OphthalmologyUNIFESP, Department of OphthalmologySciEL

Localized Populations of CD8low/− MHC Class I Tetramer+ SIV-Specific T Cells in Lymphoid Follicles and Genital Epithelium

CD8 T cells play an important role in controlling viral infections. We investigated the in situ localization of simian immunodeficiency virus (SIV)-specific T cells in lymph and genital tissues from SIV-infected macaques using MHC-class I tetramers. The majority of tetramer-binding cells localized in T cell zones and were CD8+. Curiously, small subpopulations of tetramer-binding cells that had little to no surface CD8 were detected in situ both early and late post-infection, and in both vaginally and rectally inoculated macaques. These tetramer+CD8low/− cells were more often localized in apparent B cell follicles relative to T cell zones and more often found near or within the genital epithelium than the submucosa. Cells analyzed by flow cytometry showed similar populations of cells. Further immunohistological characterization revealed small populations of tetramer+CD20− cells inside B cell follicles and that tetramer+ cells did not stain with γδ-TCR nor CD4 antibodies. Negative control tetramer staining indicated that tetramer+CD8low/− cells were not likely NK cells non-specifically binding to MHC tetramers. These findings have important implications for SIV-specific and other antigen-specific T cell function in these specific tissue locations, and suggest a model in which antigen-specific CD8+ T cells down modulate CD8 upon entering B cell follicles or the epithelial layer of tissues, or alternatively a model in which only antigen-specific CD8 T cells that down-modulate CD8 can enter B cell follicles or the epithelium

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Age-related macular degeneration with choroidal neovascularization in the setting of pre-existing geographic atrophy and ranibizumab treatment. Analysis of a case series and revision paper

PURPOSE: To report the response of choroidal neovascularization (CNV) to intravitreal ranibizumab treatment in the setting of age-related macular degeneration (AMD) with extensive pre-existing geographic atrophy (GA) and a revision paper. METHODS: This is a revision paper and a retrospective case series of 10 eyes in nine consecutive patients from a photographic database. The patients were actively treated with ranibizumab for neovascular AMD with extensive pre-existing GA. Patients were included if they had GA at or adjacent to the foveal center that was present before the development of CNV. The best corrected visual acuity and optical coherence tomography (OCT) analysis of the central macular thickness were recorded for each visit. Serial injections of ranibizumab were administered until there was resolution of any subretinal fluid clinically or on OCT. Data over the entire follow-up period were analyzed for overall visual and OCT changes. All patients had been followed for at least 2 years since diagnosis. RESULTS: The patients received an average of 6 ± 3 intravitreal injections over the treatment period. Eight eyes had reduced retinal thickening on OCT. On average, the central macular thickness was reduced by 94 ± 101 µm. Eight eyes had improvement of one or more lines of vision, where as one eye had dramatic vision loss and one had no change. The average treatment outcome for all patients was -0.07 ± 4.25 logMAR units, which corresponded to a gain of 0.6 ± 4.4 lines of Snellen acuity. The treatment resulted in a good anatomic response with the disappearance of the subretinal fluid, improved visual acuity, and stabilized final visual results. CONCLUSION: The results of this case series suggest that the use of an intravitreal anti-vascular endothelial growth factor (VEGF) agent (ranibizumab) for CNV in AMD with extensive pre-existing GA is effective. Our results are not as striking as published results from large-scale trials of anti-VEGF therapy for subfoveal CNV, presumably due to the limitation in the baseline visual acuity caused by the underlying GA. The good anatomic response with the disappearance of the subretinal fluid, improved visual acuity, and stabilized final visual results were consistent with other ranibizumab studies

Predominantly hemorrhagic choroidal neovascular lesion from exsudative age-related macular degeneration treated with intravitreal ranibizumab therapy

The authors relate a predominantly hemorrhagic choroidal neovascular lesion from neovascular. Age-related macular degeneration patient case treated with intravitreal ranibizumab therapy. Monthly ranibizumab (six intravitreal injections) displayed a promising response but this limited report is insufficient to guarantee the indication for all predominantly hemorrhagic choroidal neovascular lesion from neovascular age-related macular degeneration. Further studies will be necessary for complete validation of our results for all predominantly hemorrhagic choroidal neovascular lesions from CNV due to AMD

Intravitreal ranibizumab and bevacizumab therapy for choroidal neovascularization in age-related macular degeneration with extensive pre-existing geographic atrophy

PURPOSE: To report the response of choroidal neovascularization to intravitreal ranibizumab or bevacizumab treatment in the setting of age-related macular degeneration with extensive pre-existing geographic atrophy of the retinal pigment epithelium. METHODS: This is a retrospective case series of 11 eyes in ten consecutive patients retrieved from a photographic database. The patients were treated with ranibizumab or bevacizumab for neovascular age-related macular degeneration with pre-existing geographic atrophy. Patients were included if they had geographic atrophy at or adjacent to the foveal center of at least 1 disc area in size that was present before the development of choroidal neovascularization. The best corrected visual acuity and optical coherence tomography analysis of the central macular thickness were recorded for each visit. Serial injections of ranibizumab or bevacizumab were administered until there was complete resolution of subretinal fluid on optical coherence tomography. Data over the entire follow-up period were analyzed for overall visual and optical coherence tomography changes. RESULTS: The patients received an average of 7 ± 3 intravitreal injections over the treatment period. Seven of 11 eyes had reduced retinal thickening on optical coherence tomography. On average, the central macular thickness was reduced by 72 ± 115 µm. Six of these 7 eyes had improvement of one or more lines of vision and one had no change. The average acuity change for all patients was -0.04 ± 0.46 logMAR units, which corresponded to a gain of 0.2 ± 4.4 lines of Snellen acuity. The treatment resulted in a good anatomic response with resolution of the subretinal fluid and overall stable visual acuity. CONCLUSIONS: The results of this case series suggest that the use of an intravitreal anti-vascular endothelial growth factor (VEGF) agent (ranibizumab or bevacizumab) for choroidal neovascularization in age-related macular degeneration with pre-existing geographic atrophy is effective. Our results are not as striking as published results from large-scale trials of anti-vascular endothelial growth factor therapy for subfoveal choroidal neovascularization, presumably due to the limitation in the baseline visual acuity caused by the underlying geographic atrophy. The favorable anatomic response with the resolution of subretinal fluid and stable acuity were consistent with other ranibizumab and bevacizumab studies

Tratamento da degeneração macular relacionada à idade com neovascularização de coróide extrafoveal: análise de uma série de casos e revisão de literatura

A degeneração macular relacionada à idade (DMRI) é uma doença degenerativa da área central da retina freqüentemente associada à perda visual central, em pessoas acima de 55 anos de ambos os sexos, sendo a mais importante causa de cegueira irreversível em adultos nos países desenvolvidos e a terceira causa de cegueira no mundo. OBJETIVO: Avaliar a eficácia da injeção intravítrea de Ranibizumab (anti-VEGF) no tratamento da neovascularização de coróide não subfoveal, podendo ser extrafoveal ou justafoveal, causada pela degeneração macular relacionada à idade exsudativa e revisão da literatura. MÉTODOS: Foi realizado um estudo descritivo e transversal com avaliação de quinze pacientes com neovascularização de coróide extrafoveal ou justafoveal causada por degeneração macular relacionada à idade. Os pacientes foram tratados com uma injeção intravítrea, por mês, no mínimo por três meses consecutivos, de Ranibizumab na dose de 0,5mg, no olho com neovascularização de coróide. Os mesmos foram examinados com um mês de intervalo entre as aplicações das injeções e acompanhados com exames complementares. RESULTADOS: Os resultados da análise dos quinze pacientes que foram incluídos nesta série de casos mostraram que onze (73,3%) pacientes apresentavam neovascularização de coróide extrafoveal e quatro (26,6%) justafoveal. Oito (53,3%) apresentavam a forma oculta e sete (46,6%) tinham lesões clássicas. A média de injeções realizadas foi de 3,67, sendo o menor número de injeções 3 e o maior 6 injeções. Oito (53,3%) pacientes apresentaram resolução do quadro exsudativo neovascular com o máximo de três injeções e apenas um (6,67%) paciente necessitou de seis injeções para resolução do seu quadro. A acuidade visual máxima alcançada foi de 20/30, e ocorreu em cinco (33,3%) pacientes. A média de acuidade visual no momento do diagnóstico foi de 0,44logMAR e a média final de 0,27logMAR Na avaliação final dos pacientes após os seis meses de estudo, a média de linha de visão ganha foi de 1,87 linha de acuidade visual pela tabela de Snellen, sendo que todos os 15 pacientes ganharam uma ou mais linhas de visão. CONCLUSÃO: No tratamento dos pacientes com degeneração macular relacionada à idade e neovascularização de coróide extrafoveal a injeção de Ranibizumab mostrou-se eficaz, podendo ser a opção como indicação inicial de tratamento nestes casos