Navegando por Palavras-chave "Macular degeneration"

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    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
    (Soc Brasileira Oftalmologia, 2012-11-01) Amaro, Miguel Hage [UNIFESP]; Holler, Aaron Brock; Inst Olhos & Laser Belem; Universidade Federal de São Paulo (UNIFESP); Univ Iowa
    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 mu m. Eight eyes had improvement of one or more lines of vision, whereas 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.
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    Angiogênese da retina e coroide : biomarcadores e engenharia genética
    (Universidade Federal de São Paulo (UNIFESP), 2017-11-30) Silva, Thiago George Cabral [UNIFESP]; Mattos, Rubens Belfort [UNIFESP]; Lima, Luiz Henrique Soares Gonçalves de [UNIFESP]; Regatieri, Caio Vinicius Saito [UNIFESP]; Luiz Henrique Soares Gonçalves de Lima : http://lattes.cnpq.br/0399713306487727; Caio Vinicius Saito Regatieri : http://lattes.cnpq.br/3274977342997227; http://lattes.cnpq.br/4270399167335564; http://lattes.cnpq.br/6865877242594519; Universidade Federal de São Paulo (UNIFESP)
    Objetivo: Comparar a concentração do fator de crescimento endotelial vascular (VEGF) no humor aquoso antes e após uma única injeção intravítrea de bevacizumabe (IVB) e estudar a concentração de 19 moléculas angiogênicas antes e após três IVBs mensais em olhos com doença macular relacionada à idade (DMRI) exsudativa, apontando os principais grupos de moléculas pró e antiangiogênicas e, ainda, descrevendo tratamentos de engenharia genética como o futuro terapêutico da angiogênese ocular, em especial o uso do CRISPR. Métodos: Na primeira publicação, pacientes com DMRI exsudativa foram tratados com uma única injeção (1,25 mg/0,05 mL). Amostras de humor aquoso foram obtidas antes da injeção, em uma semana, um mês e três meses de seguimento. Na segunda publicação, pacientes com DMRI exsudativa foram tratados com IVB mensal (1,25 mg/0,05 mL). Foram analisadas as concentrações de 19 moléculas angiogênicas a partir de amostras do humor aquoso obtidas antes de cada IVB. Parâmetros clínicos foram analisados para ambos os estudos. Foi realizada uma revisão da literatura das principais moléculas relacionadas à neovascularização da retina e coroide, das terapias antiangiogênicas oculares disponíveis e de tratamentos promissores em desenvolvimento. Resultados: Na primeira publicação, os níveis do VEGF reduziram e a acuidade visual (AV) melhorou significativamente em todos os períodos de acompanhamento, quando comparados à linha de base. A menor expressão do VEGF foi observada em uma semana e a mais intensa melhora da AV ocorreu um mês após o tratamento. Todos os parâmetros avaliados na tomografia de coerência óptica (OCT) apresentaram redução significativa no primeiro mês. Na segunda publicação, observou-se uma diminuição significativa do VEGF-A nos seguimentos de um e dois meses, com aumento significativo na concentração de sete moléculas: angiopoietina-2, endotelina-1, folistatina, fator de crescimento semelhante ao fator de crescimento epidérmico de ligação à heparina, fator de crescimento de hepatócitos, interleucina-8 e fator de crescimento endotelial vascular-C. Houve melhora da AV aos dois meses e redução dos parâmetros do OCT em todos os períodos do estudo. Na terceira publicação, observaram-se 16 grupos de potenciais moléculas-alvo contra a neovascularização da retina e coroide, com 26 ensaios clínicos em andamento, sendo sete de terapias combinadas e utilização de vetores virais. A terapia genética modificou genes relacionados a doenças retinianas, diminuiu a ligação de fatores angiogênicos e a expressão do receptor do VEGF em lesões vasoproliferativas. Conclusões: Uma única IVB diminui significativamente os níveis do VEGF após uma semana do tratamento, com a melhora clínica ocorrendo após um mês. Ao analisarmos 19 moléculas, apesar da diminuição expressiva do VEGF-A, os níveis de sete moléculas pró-angiogênicas aumentaram significativamente após IVB. Não obstante a melhora na espessura da retina ocorrer logo no primeiro mês, a melhora da acuidade visual aconteceu aos dois meses. A combinação de inibição/estimulação de diferentes vias, na tentativa de controlar as complexas interações entre as moléculas relacionadas à angiogênese pode ser um futuro promissor no tratamento da neovascularização ocular. A engenharia genética, em especial o sistema CRISPR, tem potencial para se tornar um importante método no tratamento da DMRI exsudativa.
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    Aspectos da tomografia de coerência óptica na doença de Stargardt: relato de caso
    (Conselho Brasileiro de Oftalmologia, 2006-08-01) Gouveia, Enéias Bezerra [UNIFESP]; Morales, Maira Saad De Ávila [UNIFESP]; Allemann, Norma [UNIFESP]; Matte, Guilherme [UNIFESP]; Berezovsky, Adriana [UNIFESP]; Sallum, Juliana Maria Ferraz [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The term fundus flavimaculatus (Stargardt disease) describes a group of inherited macular dystrophies characterized by multiple yellow to yellow-white flecks at the level of the retinal pigment epithelium. The authors describe findings in the patient with Stargardt's disease using optical coherence tomography (OCT), and suggest the examination to be valid as subsidiary method in the study of the characteristics of the retina in Stargardt's disease patients, but studies involving a series of patients should be able to show the most frequent findings in these cases.
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    Avaliação da função macular por eletrorretinografia focal e por angiofluoresceinografia em pacientes com degeneração macular relacionada à idade neovascular submetidos à terapia fotodinâmica com verteporfina
    (Conselho Brasileiro de Oftalmologia, 2009-02-01) Oshima, Akiyoshi [UNIFESP]; Berezovsky, Adriana [UNIFESP]; Salomão, Solange Rios [UNIFESP]; Sacai, Paula Yuri [UNIFESP]; Costa, Rogerio Alves [UNIFESP]; Bordon, Arnaldo Furman; Farah, Michel Eid [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Hospital Oftalmológico de Sorocaba Setor de Retina e Vítreo
    PURPOSE: To evaluate macular function by focal electroretinography and fluorescein angiography (FA) in patients with neovascular age-related macular degeneration submitted to verteporfin photodynamic therapy (VPT). METHODS: Prospective study involving 22 patients with age-related macular degeneration and predominantly classic subfoveal neovascular membrane, in non consecutive series, treated with VPT and followed for 12 months. They had their best corrected visual acuity measured by ETDRS chart, changes of lesion measured by fluorescein angiography and cone function assessed by focal electroretinography at baseline and each 3month follow-up. RESULTS: All 22 patients completed the scheduled follow-up. After a mean of 3.5 sessions of treatment per patient, the mean visual acuity variation was not significant at the end of study. Eleven patients showed variation >1 line. 86% of patients achieved stabilization of lesion leakage at the end of the study. Focal electroretinography showed a mean of 194.88 nV in amplitude and 29.19 ms in latency and did not present a significant variation during treatment. CONCLUSIONS: There were no significant differences in focal electroretinography amplitudes and latencies after a 9-month period. Visual acuity did not show important variations during the 12 months. The decrease of lesion size showed a significant difference at 12 months with negative correlation between the amplitude of focal electroretinography and best corrected visual acuity.
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    Avaliação da tomografia de coerência óptica em pacientes portadores de degeneração macular relacionada à idade tratada com terapia fotodinâmica com verteporfina
    (Conselho Brasileiro de Oftalmologia, 2008-12-01) Bordon, Arnaldo Furman [UNIFESP]; Oshima, Akioshi [UNIFESP]; Guia, Tércio Alves [UNIFESP]; Calucci, Daniela [UNIFESP]; Sallum, Juliana Maria Ferraz [UNIFESP]; Farah, Michel Eid [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    PURPOSE: To identify the optical coherence tomography (OCT) findings in patients with age-related macular degeneration (ARMD) treated with photodynamic therapy (PDT). STUDY DESIGN: Open, non-randomized, interventional case series. METHODS: ARMD patients were submitted to a complete ophthalmological examination, fluorescein angiography, and OCT at baseline (V0), 3, 6, 9 and 12 months (V3, V6, V9 and V12, respectively). PDT was carried out according to the TAP study. Visual acuity (VA) was measured using the logMAR ETDRS chart. The following foveal measurements were performed: foveal intraretinal thickness (FIRT), foveal choriocapillaris - RPE complex thickness (FCC-RPET) and total foveal thickness (TFT). The extrafoveal thicknesses measured were: extrafoveal intraretinal thickness (EFIRT), extrafoveal choriocapillaris - RPE complex thickness (EFCC-RPET) and total extrafoveal thickness (TEFT). Statistical analysis was performed using the block variance analysis test. RESULTS: Twenty-three eyes of 23 patients were enrolled. This study identified nine OCT patterns: 1) thickening of the foveal intraretinal layers; 2) thickening of the extrafoveal intraretinal layers; 3) thickening of the foveal choriocapillaris - RPE complex; 4) thickening of the extrafoveal choriocapillaris - RPE complex; 5) intraretinal fluid; 6) subretinal fluid; 7) subretinal pigment epithelium (RPE) fluid; 8) vitreo-retinal adhesion; 9) foveal depression. At baseline, FIRT and TFT were 398.5 µ and 639.2 µ, respectively. At V12 they were 173.7 µ e 423.9 µ, respectively, and this change was statistical significant (p=0.008 e p=0.003, respectively). The variation of the other foveal and extrafoveal measurements were not statistically significant. Foveal depression was present at baseline in 36.4% of the eyes, whereas at V12 it was present in 78.3%. Subretinal fluid was present in 36.4% of eyes at V0 and in 8.7% at V12. VA at baseline was 0.93 and it V12 was 1.04 (p=0,127). CONCLUSIONS: Visual acuity was stable throughout the study. Foveal depression was reestablished in 78.3% at V12. FIRT and TFT decreased at a statistical significant level, from V0 to V12.
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    Avaliação das alterações precoces na coróide e esclera ocorridas em coelhos hipercolesterolêmicos: estudo histológico e histomorfométrico
    (Conselho Brasileiro de Oftalmologia, 2009-02-01) Torres, Rogil José de Almeida [UNIFESP]; Maia, Maurício [UNIFESP]; Noronha, Lucia; Farah, Michel Eid [UNIFESP]; Luchini, Andréa; Brik, Décio; Muccioli, Cristina [UNIFESP]; Précoma, Dalton Bertolin; Universidade Federal de São Paulo (UNIFESP); Universidade Federal dHospital de Olhos Oeste Paulistae São Paulo Serviço de Cirurgia Vitreorretiniana; Pontifícia Universidade Católica do Paraná Departamento de Patologia; Centro Oftalmológico de Curitiba; Hospital Angelina Caron; Pontifícia Universidade Católica do Paraná Departamento de Cardiologia
    PURPOSE: To demonstrate experimentally, by means of histological and histomorphometric examinations, the sclera and choroid degenerative alterations, which take place at an early stage due to a hypercholesterolemic diet. METHODS: New Zealand rabbits were divided into two groups: CG (control group) of 6 rabbits (6 eyes) received a regular diet for 6 weeks; G1, of 12 rabbits (12 eyes), was first fed a 1% cholesterol diet (Sigma-Aldrich) for 2 weeks and then from the 14th day on a 0.5% cholesterol diet (Sigma-Aldrich). The eyes underwent a histological analysis, stained with hematoxiline-eosine, and a morphometric examination. The histomorphometric analysis was performed in the posterior region, adjacent to the optic disk, and in the peripheral region. RESULTS: The CG presented a mean sclera and choroid thickness of 228.61 ± 31.71 micrometers in the peripheral region, while the thickness in the posterior region was approximately 246.07 ± 25.66 micrometers. In G1, these values were 303.56 ± 44.21 micrometers in the peripheral region and 295.59 ± 62.59 in the posterior region. There was a statistically significant difference in the sclera and choroid thickness between the groups in the peripheral region (p<0.001); however, this difference did not occur in the posterior region (p=0.250). The large number of histiocytes and collagen fibers accounted for the increase of G1 wall thickness in relation to CG. CONCLUSION: This study demonstrated that the hypercholesterolemic diet in rabbits induces a fast increase in the choroid and sclera thickness, mainly due to the increase in the number of histiocytes and collagen fibers.
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    Avaliação das anormalidades precoces esclerocoriorretinianas observadas em coelhos hipercolesterolemicos tratados com Rosiglitazona
    (Universidade Federal de São Paulo (UNIFESP), 2010-04-28) Torres, Rogil José de Almeida [UNIFESP]; Muccioli, Cristina [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The purpose of this study is to evaluate scleral, choroid and retinal abnormalities in rabbits induced by a hypercholesterolemic diet and the prevention of these abnormalities after oral administration of rosiglitazone in rabbits. Fifty-four new zealand rabbits were divided into four groups: the control group (CG) was fed a normal diet; group 1 G1), a hypercholesterolemic diet; group 2 (G2) a hypercholesterolemic diet associated with daily administration of 3 mg of rosiglitazone from day 14 after the beginning of the diet; and group 3 G3), a hypercholesterolemic diet associated with daily administration of 3 mg of rosiglitazone since the beginning of the experiment. The rabbits were weighed and underwent the following examinations: seric dosages of total cholesterol, triglycerides, cholesterol HDL, and fasting glycemia at the beginning of the experiment, on the 14th day and on the 42nd, the euthanasia day. The sclera and choroid underwent histologic and histomorphometric analyses and the retina underwent immunohistochemical analysis with anti-calretinin (CR) and anti-glial fibrillary acidic protein (GFAP) antibody. When positive for the anti-calretinin marker, two quantitative analyses were performed. In the first analysis, all immunoreactive ganglion cells were counted. In the second analysis, all immunoreactive cells and cell elements were studied with the color morphometry method. The data were evaluated using the nonparametric Kruskal-Wallis and the Shapiro – Wilk tests. Values of p<0.05 were considered statistically significant. The results obtained showed a significant weight increase in Groups 1 and 3 in relation to CG on Day 14 (p<0.009). Additionally, a significant weight increase was observed in G1, G2 and G3 in relation to CG on Day 42 (p<0.023). The lab results showed a significant increase in glucose and total cholesterol in G1 in relation to CG (p<0.001) on Day 14, as well as a significant HDL increase in G3, when compared with the other groups (p<0.001) on Day 14. HDL in G3 was significantly high when compared to the other groups, on the euthanasia day (p<0.001). The results obtained regarding weight showed a significant increase in Groups 1, 2 and 3 in relation to CG on Day 14 (p<0.01) and Day 42 (p<0.02). The lab results showed a significant increase in glucose and total cholesterol in Groups 1, 2 and 3 in relation to CG (p<0.01) on Day 14, as well as a significant increase in HDL in G3 when compared with the other groups, on euthanasia day (p<0.01). The histomorphometric analysis of CG sclera and choroid presented normal results. Conversely, G1 showed a significant increase in sclera and choroid thickness in relation to CG (p= 0,008), whereas G3 showed thickness lower than in G1 (p=0,048). A larger number of histiocytes were observed on the scleral wall of the group that was fed the hypercholesterolemic diet (G1), followed, in a descending order, by groups 2 and 3, and the control group. The immunohistochemical analysis of the retina with the anti-calretinin monoclonal antibody showed that G1 presented a larger number of immunoreactive ganglion cells than G3 (p = 0.002). The color morphometry showed significant immunoreactivity of G1 cells and cell elements when compared with the other groups (p<0.001). A significant immunoreactivity of G2 and G3 cells and cell elements in relation to CG was also observed (p<0.002). GFAP results were negative in all groups. The findings of this proposed study model suggest that hypercholesterolemia induces early histomorphometric and immunohistochemical abnormalities in the sclerochorioretinal complex and that the activation of PPAR gamma in ocular cells attenuated these abnormalities with the administration of the oral rosiglitazone diet.
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    Bevacizumab for ocular neovascular diseases: a systematic review
    (Associação Paulista de Medicina - APM, 2009-05-01) Andriolo, Regis Bruni [UNIFESP]; Puga, Maria Eduarda dos Santos [UNIFESP]; Belfort, Rubens Junior [UNIFESP]; Atallah, Álvaro Nagib [UNIFESP]; Brazilian Cochrane Center; Universidade Federal de São Paulo (UNIFESP)
    CONTEXT AND OBJECTIVE: Many eye diseases involve increased local levels of vascular endothelial growth factor (VEGF), and there are several therapeutic strategies for them. Thus, the aim of this study was to evaluate the effectiveness and safety of bevacizumab for treating eye diseases involving increased local levels of VEGF, as the assumed pathophysiological mechanism. DATA SOURCES: The following databases were systematically searched for evidence: PubMed, CENTRAL (Cochrane Library), Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs) and reference lists, without language restrictions. Only randomized controlled trials were included. The primary outcome of interest was visual acuity, irrespective of the evaluation method. DATA SYNTHESIS: A total of 667 eyes in nine randomized trials were included. Meta-analysis showed that the proportion of patients with age-related macular degeneration who presented improvements from baseline regarding best-corrected visual acuity was higher among those treated with bevacizumab than among those in the photodynamic therapy group (risk ratio, RR, 0.49; 95% confidence interval, CI, 0.31 to 0.78; P = 0.01). CONCLUSIONS: The evidence available demonstrates that bevacizumab alone or combined with other treatments is more effective than other options, including photodynamic therapy, focal photocoagulation and triamcinolone. The use of bevacizumab instead of photodynamic therapy could reduce treatment costs by more than 99% and could significantly increase access to treatment. However, long-term studies are still needed in order to reduce uncertainty concerning the safety of this medication for all ocular neovascular diseases in which bevacizumab has the potential to improve visual acuity.
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    Comparação do efeito antiangiogênico do ranibizumab e do bevacizumab in vitro
    (Conselho Brasileiro de Oftalmologia, 2011-10-01) Souto, Alexandre Cupello [UNIFESP]; Maricato, Juliana Terzi [UNIFESP]; Denapoli, Priscila Martins Andrade [UNIFESP]; Sallum, Juliana Maria Ferraz [UNIFESP]; Han, Sang Won [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Purpose: To evaluate the comparative in-vitro antiangiogenic effect of Bevacizumab and Ranibizumab. Methods: Endothelial venous umbilical cells culture (ECV304) cultivated in F12 media with addition of 10% Fetal Bovine Serum, were plaqued and treated with clinically relevant concentrations of Bevacizumab and Ranibizumab just after the scratch done in the middle of the culture (scratch methodology). Measurements of the linear size of the area free of cell proliferation were done 24, 48 and 72 hours after the scratch day point. All the experiments were done in triplicate and statistical analysis were done with T-student test. Results: Inhibitory effect was observed just at the concentrations of 0.5 and 0.7 mg/ml in both drugs. At 0.7 mg/ml, Ranibizumab demonstrated a more potent proliferative inhibitory effect than Bevacizumab. At the same concentration, Ranibizumab was three times more potent than Ranibizumab. Inhibitory effect was observed just in the first 24 hours for both drugs. Conclusion: Ranibizumab demonstrates an increased effect when compared to Bevacizumab and this is related more to the different molar rate of each drug than related to a real better proliferative inhibitory effect.
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    Conceitos atuais e perspectivas na prevenção da degeneração macular relacionada à idade
    (Sociedade Brasileira de Oftalmologia, 2008-06-01) Torres, Rogil José De Almeida [UNIFESP]; Précoma, Dalton Bertolim; Maia, Maurício [UNIFESP]; Kaiber, Flávia; Prim, Camila; Luchini, Andréa; Matos, Rossane Serafin; Farah, Michel Eid [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Hospital Angelina Caron; Pontifícia Universidade Católica do Paraná Departamento de Cardiologia; Hospital de Olhos Oeste Paulista Serviço de Cirurgia Vitreorretiniana; Pontifícia Universidade Católica do Paraná; Nutrimedical Curitiba; Centro Oftalmológico de Curitiba
    The authors prepare a literature review about the main antioxidants used in daily practice for the prevention of age-related macular degeneration progression (AMD), emphasizing the mechanism of action of each substance as well as the possible complications related to the overuse of such components.
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    Degeneração macular relacionada à idade: modalidades terapêuticas
    (Conselho Brasileiro de Oftalmologia, 2001-11-01) Farah, Michel Eid [UNIFESP]; Oshima, Akiyoshi [UNIFESP]; Costa, Rogerio Alves [UNIFESP]; Sallum, Juliana Ferraz [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    To describe the clinical and surgical therapeutic modalities in age-related macular degeneration (ARMD).
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    Estudo de toxicidade retiniana após injeções intravítreas seriadas de infliximabe em olhos de coelhos
    (Conselho Brasileiro de Oftalmologia, 2011-10-01) Rassi, Alan Ricardo; Rigueiro, Moacyr Pezati [UNIFESP]; Isaac, David Leonardo Cruvinel; Dourado, Letícia [UNIFESP]; Abud, Murilo Batista; Freitas, Éricka Campos; Carneiro, Luciana Barbosa; Ávila, Marcos Pereira de; Universidade Federal de Goiás Centro de Referência em Oftalmologia Ophthalmology Department; Universidade Federal de São Paulo (UNIFESP); Universidade Federal de Goiás Centro de Referência em Oftalmologia Setor de Retina e Vítreo; Universidade Federal de Goiás Centro de Referência em Oftalmologia Setor de Eletrofisiologia
    PURPOSE: To determine retinal and choroid toxicity levels of two and three infliximab intravitreous injections in albino rabbits by means of electroretinographic, histological and ophthalmological clinical tests. METHODS: 12 albino rabbits were used in the study. Each eye was given two (n=10 eyes) or three (n=10 eyes) serial intravitreous 2 mg infliximab injections dissolved in 0.06 ml of saline, at monthly intervals. A separate group of rabbits (n=4 eyes) served as a control group. Ninety days after the study had begun, the rabbits underwent clinical and electroretinographic tests, and after being enucleated, the eyes were examined for histological changes. RESULTS: Slit-lamp biomicroscopy and fundoscopic examination did not reveal any significant retinal abnormalities in the eyes injected with infliximab and control eyes or in pre- and post-treated eyes. The histological change that was noted was the presence of rare lymphocytes and eosinophils in the posterior vitreous of some of the rabbits subjected to two or three injections, but it was not considered clinically significant. A severe inflammatory reaction with vitreous exudates and ganglion cell edema in a single rabbit was clinically significant. The electroretinographic tests showed amplitudes that were on the average 12-13% smaller than those obtained before the treatment, however, there were no statistically significant differences when comparing the amplitude or the implicit time between pre- and post-treatment electroretinographic findings. CONCLUSION: Two and three intravitreous 2 mg infliximab injections in rabbits at monthly intervals did not cause any changes after a 90-day follow-up, according to histological and electroretinographic tests and after clinical evaluation. Differently from prior studies that have investigated potential retinotoxicity effects after single administrations, this study investigated the possibility of retinotoxicity after multiple injections. Clinical studies in humans should be conducted to better evaluate the safety of this drug in the treatment of certain diseases affecting the retina and the choroid.
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    Fatores modificáveis da degeneração macular relacionada à idade
    (Conselho Brasileiro de Oftalmologia, 2009-06-01) Torres, Rogil José De Almeida [UNIFESP]; Maia, Maurício [UNIFESP]; Muccioli, Cristina [UNIFESP]; Winter, Guilherme; Souza, Greyce Kelly De; Pasqualotto, Luca Rodrigo; Luchini, Andréa; Précoma, Dalton Bertolim; Hospital Angelina Caron; Universidade Federal de São Paulo (UNIFESP); Hospital de Olhos Oeste Paulista Serviço de Cirurgia Vitreorretiniana; Pontifícia Universidade Católica do Paraná; PUCPR; Centro Oftalmológico de Curitiba; PUCPR Departamento de Cardiologia
    The authors present the main modifiable risk factors that may trigger and/or worsen age-related macular degeneration. Mechanisms of action related to these factors as well as preventive measures and intervention effectiveness are discussed.
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    Implante celular do epitélio pigmentar da retina derivado de células-tronco embrionárias em um modelo murino: princípios para a terapia regenerativa celular em humanos
    (Universidade Federal de São Paulo (UNIFESP), 2016-11-29) Ribeiro, Ramiro Magalhães [UNIFESP]; Maia, Mauricio [UNIFESP]; http://lattes.cnpq.br/6377105744231862; http://lattes.cnpq.br/9793000308103027; Universidade Federal de São Paulo (UNIFESP)
    Objective: to demonstrate the principle of cellular therapy after the implantation of retinal pigmented epithelial cells (RPE) derived from embryonic stem-cells (here denominated hESC-RPE) seeded in a parylene-C membrane in a murine animal model. Method: after the implant of the cell into the murine animal, four different studies were done. In the first study, analysis of histology and optical coherence images (OCT) were performed immediately (n=6) or seven days (n=5) after the implant. In the second study, monthly infrared imagens and OCT were obtained in animals that received the implant (n=14) and control group (parylene-C membrane without the presence of cells, n=14). The images were correlated and compared with histology findings. In the third study, histological analyses were performed in ocular and extra-ocular tissue in an immunocompromised animal (n=36). The cellular survival rate and the tumor formation were compared with a group of animals (n=33) that received the implant of hESC-RPE as a cell suspension. In the fourth study, the visual behavioral response and quantification of the photoreceptors were analyzed in animals with progressive degenerative retina disease after the implant of cells (n=20) and compared with a surgical control group (n=10) and untreated group (fellow eye). Animals implanted with the hESC-RPE as a cell suspension (n=18) were also evaluated. Results: OCT images, microscopy and histology demonstrated the successful surgical implantation leading to a small cell lost (less than 2%). Infrared images identified in-vivo areas corresponded with the implanted cells and those findings were confirmed by histology and specific markers. No areas corresponding with hESC-RPE was identified in animals that received the implant of parylene without the cells. Histology analysis demonstrated the cell survival for a period of up to one year and confirmed the non-formation of ocular and extra-ocular tumor. The survival rate was superior in the animals that received the implant of hESC-RPE/parylene compared with the injection group. The animals implanted with the hESC-RPE cells demonstrated a better visual response between the 4th and 25th weeks after the implant. Afterwards, no visual response was detected in any of the animals. The hESC-RPE also led to a better preservation of the photoreceptors. Conclusion: The implant of hESC-RPE cells seeded in a parylene-C membrane into the subretinal space was viable, imagining studies detected the presence of in-vivo cells and its correlation with histology findings were positive, the cells survived for a period up to one year and did not lead to formation of tumors and the implantation of the cells were able to slow the progression of visual lost and retina degeneration.
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    Influence of blue light spectrum filter on short-wavelength and standard automated perimetries
    (Conselho Brasileiro de Oftalmologia, 2006-10-01) Castro, Leonardo Cunha [UNIFESP]; Souza, Carlos Eduardo Barbosa de [UNIFESP]; Soriano, Eduardo Sone [UNIFESP]; Melo Jr., Luiz Alberto Soares [UNIFESP]; Paranhos Junior, Augusto [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    PURPOSE: To evaluate the influence of a blue light spectrum filter (BLSF), similar in light spectrum transmittance to the intraocular lens Acrysof NaturalTM, on standard automated perimetry (SAP) and short-wavelength automated perimetry (SWAP). METHODS: Twenty young individuals (<30 y.o.), without any systemic or ocular alterations (twenty eyes) underwent a random sequence of four Humphrey visual field tests: standard automated perimetry (SAP) and short-wavelength automated perimetry (SWAP) with and without a blue light spectrum filter. All patients had intraocular pressure lower than 21 mmHg, normal fundus biomicroscopy, and no crystalline lens opacity. Foveal threshold (FT), mean deviation (MD), and pattern standard deviation (PSD) indexes obtained from the visual field tests and the difference caused by eccentricity in short-wavelength automated perimetry examinations were analyzed using paired t test. Interindividual variability (standard deviation) was calculated using Pitman's test for correlated samples. RESULTS: Statistically significant reductions in the mean deviation (p<0.001) and in the foveal threshold (p<0.001) measured by short-wavelength automated perimetry with the use of the blue light spectrum filter in comparison to short-wavelength automated perimetry without the use of the blue light spectrum filter were observed, but not in standard automated perimetry exams. No other parameters showed statistically significant differences in the short-wavelength automated perimetry and standard automated perimetry tests. Interindividual standard deviation of the test points in the short-wavelength automated perimetry exams increased with eccentricity both with and without the use of the blue light spectrum filter, as sensitivity for inferior and superior hemifields (inferior hemifield minus superior hemifield), but no statistically significant difference in the variability when comparing the use or not of the blue light spectrum filter was noted. When comparing only the four most inferior points and the four most superior points, the inferior-superior difference increases in both situations - without and with the use of the blue light spectrum filter. The difference between without and with the use of the blue light spectrum filter was not statistically significant. CONCLUSION: Statistically significant reductions in mean deviation and foveal threshold in the short-wavelength automated perimetry with the use of the blue light spectrum filter were observed, but not in standard automated perimetry examinations. Additional studies are necessary to determine the influence of intraocular lenses with short-wavelength light filter after cataract extraction on short-wavelength automated perimetry.
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    Intravitreal ranibizumab and bevacizumab for the treatment of nonsubfoveal choroidal neovascularization in age-related macular degeneration
    (Conselho Brasileiro de Oftalmologia, 2009-10-01) Roller, Aaron Brock; Amaro, Miguel Hage [UNIFESP]; University of Iowa Department of Ophthalmology Hospitals and Clinics; Universidade Federal de São Paulo (UNIFESP)
    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.
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    Segurança de ziv-aflibercepte intravítreo
    (Universidade Federal de São Paulo (UNIFESP), 2017-07-31) Dias, João Rafael de Oliveira [UNIFESP]; Rodrigues, Eduardo Büchele [UNIFESP]; http://lattes.cnpq.br/4226917385383502; http://lattes.cnpq.br/1771359823403580; Universidade Federal de São Paulo (UNIFESP)
    Purpose: 1. To evaluate the viability of ARPE-19 human retinal pigment epithelial cells after exposure to ziv-aflibercept 12.5 and 25 mg/mL; 2. To evaluate the safety of intravitreal ziv-aflibercept in an experimental rabbit model; 3. To evaluate the clinical and electrophysiological safety of intravitreal ziv-aflibercept in patients with exudative age-related macular degeneration. Methods: In the first study, the ARPE-19 cells were exposed for 10 minutes and 24 hours to the two concentrations of ziv-aflibercept; balanced salt solution (BSS) and culture mean were used as controls. The effect of ziv-aflibercept on the cellular viability was analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT). All experiments were performed in triplicate and repeated three times. In the second study, pigmented rabbits (chinchilla breed) underwent a fundus examination, fundus imaging, full-field electroretinography (ERG), and optical coherence tomography (OCT) at baseline and 24 hours or 7 days after an intravitreal injection of 0.05 mL of ziv-aflibercept (25 mg/mL; n=9) or aflibercept (40 mg/mL; n=9) in the right eye and BSS in the left eye. Serum, aqueous, and vitreous specimens were obtained at baseline and 24 hours or 7 days after the intravitreal injection for osmolality analysis. After euthanasia and enucleation, both eyes of each animal were analyzed by light microscopy and transmission electron microscopy 24 hours or 7 days after the intravitreal injections. In the third study, patients with unilateral exudative age-related macular degeneration received three monthly intravitreal injections of 0.05 mL of ziv-aflibercept (25 mg/mL) followed by as-needed treatment. The safety of intravitreal ziv-aflibercept was determined by the results of full-field ERG, and the efficacy was determined by the best-corrected visual acuity measurements, OCT imaging, and multifocal ERG. The safety and efficacy parameters were evaluated at 26 and 52 weeks. Results: Neither the 12.5 or 25 mg/mL concentrations of ziv-aflibercept reduced the cellular viability in the MTT assay compared to the controls. In the experimental rabbit study, all eyes had normal fundus examinations, OCT imaging, and full-field ERGs 24 hours or 7 days after the intravitreal injection of 0.05 mL of ziv-aflibercept (25 mg/mL), aflibercept (40 mg/mL) or BSS. There were no significant changes in the mean serum, aqueous, and vitreous osmolalities. Light microscopy and transmission electron microscopy showed no major signs of toxicity compared to aflibercept. In the third study, 15 patients completed the 26-week follow-up and 14 patients completed the 52-week follow-up. Intravitreal ziv-aflibercept injections significantly improved the visual acuity, increased the multifocal ERG amplitudes within the central 0o to 15o degrees, and decreased the central macular thickness and total macular volume seen on OCT imaging 26 weeks after the intravitreal ziv-aflibercept injections. No signs of retinal toxicity were seen in full-field ERGs and no ocular or systemic adverse events developed 26 weeks after treatment with intravitreal ziv-aflibercept. A comparison between baseline and 52 weeks showed an increase in the mean visual acuity, an increase in multifocal ERG amplitudes within the central 5o, and significant reductions in the central macular thickness and total macular volume. There was a decrease in the mean amplitude of the a-wave, an increase in the mean implicit time of the a-wave in the full-field ERG, and a decrease in the mean amplitude of the 30-Hz flicker, which did not differ significantly when the treated eye was compared to the fellow eye. One patient presented with anterior segment and vitreous inflammation 4 days after one injection, the signs and symptoms of which resolved completely after treatment with topical and systemic steroids. One patient developed posterior subcapsular cataract during the follow-up. Conclusions: Neither concentrations of ziv-aflibercept reduced the cellular viability compared to controls, and the intravitreal injection of ziv-aflibercept 25 mg/mL was safe in the rabbit retina. The human study showed improvements in the visual acuity 26 and 52 weeks after the beginning of the treatment with intravitreal ziv-aflibercept. The central macular thickness and total macular volume improved 26 and 52 weeks after the beginning of the treatment with intravitreal ziv-aflibercept. No findings suggested retinal toxicity on full-field ERG 26 and 52 weeks after the beginning of the treatment with intravitreal ziv-aflibercept.
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    Subretinal implantation of a monolayer of human embryonic stem cell-derived retinal pigment epithelium: a feasibility and safety study in Yucatan minipigs
    (Springer, 2016) Koss, Michael J.; Falabella, Paulo; Stefanini, Francisco R. [UNIFESP]; Pfister, Marcel; Thomas, Biju B.; Kashani, Amir H.; Brant, Rodrigo [UNIFESP]; Zhu, Danhong; Clegg, Dennis O.; Hinton, David R.; Humayun, Mark S.
    A subretinal implant termed CPCB-RPE1 is currently being developed to surgically replace dystrophic RPE in patients with dry age-related macular degeneration (AMD) and severe vision loss. CPCB-RPE1 is composed of a terminally differentiated, polarized human embryonic stem cell-derived RPE (hESC-RPE) monolayer pre-grown on a biocompatible, mesh-supported submicron parylene C membrane. The objective of the present delivery study was to assess the feasibility and 1-month safety of CPCB-RPE1 implantation in Yucatan minipigs, whose eyes are similar to human eyes in size and gross retinal anatomy. This was a prospective, partially blinded, randomized study in 14 normal-sighted female Yucatan minipigs (aged 2 months, weighing 24-35 kg). Surgeons were blinded to the randomization codes and postoperative and post-mortem assessments were performed in a blinded manner. Eleven minipigs received CPCB-RPE1 while three control minipigs underwent sham surgery that generated subretinal blebs. All animals except two sham controls received combined local (Ozurdex (TM) dexamethasone intravitreal implant) and systemic (tacrolimus) immunosuppression or local immunosuppression alone. Correct placement of the CPCB-RPE1 implant was assessed by in vivo optical coherence tomography and post-mortem histology. hESC-RPE cells were identified using immunohistochemistry staining for TRA-1-85 (a human marker) and RPE65 (an RPE marker). As the study results of primary interest were nonnumerical no statistical analysis or tests were conducted. CPCB-RPE1 implants were reliably placed, without implant breakage, in the subretinal space of the minipig eye using surgical techniques similar to those that would be used in humans. Histologically, hESC-RPE cells were found to survive as an intact monolayer for 1 month based on immunohistochemistry staining for TRA-1-85 and RPE65. Although inconclusive regarding the necessity or benefit of systemic or local immunosuppression, our study demonstrates the feasibility and safety of CPCB-RPE1 subretinal implantation in a comparable animal model and provides an encouraging starting point for human studies.
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    Técnica para injeção intravítrea de drogas no tratamento de doenças vítreorretinianas
    (Conselho Brasileiro de Oftalmologia, 2008-12-01) Rodrigues, Eduardo Buchele [UNIFESP]; Maia, Maurício [UNIFESP]; Penha, Fernando Marcondes [UNIFESP]; Dib, Eduardo [UNIFESP]; Bordon, Arnaldo Furman [UNIFESP]; Magalhães Júnior, Octaviano [UNIFESP]; Farah, Michel Eid [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Intravitreal injections are the standard technique applied in the treatment of some vitreoretinal diseases. In this paper the technique and complications of intravitreal injections are presented. In summary, the procedure involves various consecutive steps. Initially, days before the treatment topical antibiotics and acetazolamide may be prescribed for reduction of the ocular flora and intraocular pressure. Before the injection, the pupil should be dilated and topical anesthesia should be achieved. Injection shall be performed in the operating room under sterile conditions, the surgeon should wear surgical gloves and mask. The eye is then exposed with sterile blepharostat and sterile-drape thereby providing protection of the needle against the contact with contaminated lashes and lids. Injection is done 3.5 mm from the limbus through the pars plana. The needle should be inserted up to 6 mm into the vitreous cavity. Immediately after injection the patient must be examined by indirect ophthalmoscopy to verify central artery perfusion and complications as vitreous hemorrhage. Visual acuity better than light perception should be detected right after injection. If persistent central retinal artery occlusion is diagnosed, anterior chamber paracentesis should be performed. The patient may be discharged with an occlusive patch. Examination at the first postoperative day should exclude various complications such as endophthalmitis, and topical steroid and antibiotics should be prescribed for 7 days. Some complications encountered after intravitreal injections include retinal detachment, vitreous hemorrhage, cataract, uveitis, ocular hypertension, or endophthalmitis.
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    Vasculopatia polipoidal idiopática da coróide: aspectos extremos da evolução da doença em um paciente - Relato de caso
    (Conselho Brasileiro de Oftalmologia, 2005-04-01) Barreira, Ieda Maria Alexandre [UNIFESP]; Aragão, Ricardo Evangelista Marrocos De; Vale, Ariosto Bezerra [UNIFESP]; Holanda Filha, Joana Gurgel; Universidade Federal de São Paulo (UNIFESP); Universidade de Regensburg; Universidade Federal do Ceará Hospital Universitário Walter Cantídeo; Universidade Federal do Ceará Faculdade de Medicina; Hospital de Olhos Dr. René Barreira; Universidade Federal do Ceará Hospital Universitário Walter Cantídeo Serviço de Oftalmologia
    To describe a case of idiopathic polypoidal choroidal vasculopathy and the role of indocyanine green angiography findings in the differential diagnosis of exsudative maculopathies, particularly with age-related macular degeneration, and the extreme evolution of idiopathic polypoidal choroidal vasculopathy in one patient. A patient with vitreous hemorrhage was examined and evaluated by fluorescein and indocyanine green angiographies in the right eye and with hemorrhagic detachment of the retinal pigment epithelium in the left eye. The patient was treated by pars plana vitrectomy in the right eye which was followed by retinal detachment and vision loss. In the left eye an involution of the hemorrhagic detachment of the retinal pigment epithelium with preservation of the vision was seen. The idiopathic polypoidal choroidal vasculopathy seems to be a distinct clinical entity that can and should be differentiated from age-related macular degeneration and the fluorescein and indocyanine green angiographies should be performed to evaluate the choroidal vasculature in an attempt to establish a more definitive diagnosis. Particularly in this case the entity had an extreme clinical course in the patient.