RESUMO
PURPOSE: Mycophenolic acid (MPA) is an immunosuppressive agent that controls noninfectious uveitis. Intravitreal MPA delivery may be a potential adjuvant therapy in patients who have to discontinue steroid or immunosuppressive systemic therapy because of side effects. The aims of this study are to evaluate the in vitro effects of MPA over human retinal pigment epithelium (ARPE-19) and human Muller cells (MIO M-1). METHODS: ARPE-19 cells and MIO M-1 cells were exposed to 25, 50, and 100 µg/mL of MPA (Roche Bioscience, Palo Alto, CA) for 24 hours. Toxicity was evaluated by trypan blue dye-exclusion cell viability assay, caspase-3/7 apoptosis-related assay, and JC-1 mitochondrial membrane potential assay. RESULTS: The MPA (25 µg/mL and 50 µg/mL) did not cause reduction in cell viability or significant change in caspase-3/7 activity in both cell lines tested. Mycophenolic acid (100 µg/mL) caused a significant decrease in cell viability (P < 0.01) and higher caspase-3/7 activity (P < 0.05) in both cell lines compared with untreated cells. The JC-1 mitochondrial membrane potential did not show statistically significant differences for both cell lines and all concentration tested when compared with untreated controls (P > 0.05). CONCLUSION: Intraocular delivery may be a potential alternative for the treatment of noninfectious uveitis, either by intravitreal injection or sustained-release drug-delivery systems, in doses of 50 µg/mL or lower.
Assuntos
Inibidores Enzimáticos/toxicidade , Células Ependimogliais/efeitos dos fármacos , Ácido Micofenólico/toxicidade , Epitélio Pigmentado da Retina/efeitos dos fármacos , Benzimidazóis/farmacologia , Carbocianinas/farmacologia , Caspase 3/metabolismo , Caspase 7/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Ependimogliais/enzimologia , Células Ependimogliais/patologia , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Epitélio Pigmentado da Retina/enzimologia , Epitélio Pigmentado da Retina/patologia , Azul Tripano/metabolismoRESUMO
Purpose: To report a case of unilateral acute idiopathic maculopathy (UAIM) following vaccination for type A influenza virus (H1N1).Methods: Clinical, fundus autofluorescence (FAF), fluorescein angiography (FA) and optical coherence tomography (OCT) findings are presented.Results: A 25-year old white male presented with an acute decrease of vision in his left eye eight days after immunization with influenza A vaccine. Clinical evaluation revealed a deep yellowish-white lesion at the macula, early hyperfluorescence at the level of retinal pigment epithelium (RPE), and leakage and staining during the late phase of FA. OCT demonstrated disruption of the photoreceptor ellipsoid zone, as well as heterogeneous reflectivity changes and thickening at the level of the outer retina-RPE. Three months after presentation, fundus examination showed resolution of the yellowish foveal lesion, with persistence of mild RPE atrophic changes.Conclusion: This is the first reported case of UAIM following H1N1 vaccination to date.
Assuntos
Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/efeitos adversos , Degeneração Macular/induzido quimicamente , Vacinação/efeitos adversos , Transtornos da Visão/induzido quimicamente , Doença Aguda , Adulto , Angiofluoresceinografia , Humanos , Influenza Humana/prevenção & controle , Degeneração Macular/diagnóstico , Degeneração Macular/fisiopatologia , Masculino , Imagem Óptica , Tomografia de Coerência Óptica , Transtornos da Visão/diagnóstico , Transtornos da Visão/fisiopatologia , Acuidade Visual/fisiologiaRESUMO
OBJECTIVE: to determine the functional and morphological effects at rabbits retina of PS80 concentration used in the preparation of intravitreal drugs. METHODS: eleven New Zealand rabbits received a intravitreal injection of 0.1ml of PS80. As control, the contralateral eye of each rabbit received the same volume of saline. Electroretinography was performed according to a modified protocol, as well as biomicroscopy and retina mapping before injection and seven and ten days after. Animals were euthanized in the 30th day and the retinas were analyzed by light microscopy. RESULTS: eyes injected with PS80 did not present clinical signs of intraocular inflammation. Electroretinography did not show any alteration of extent and implicit time of a and b waves at scotopic and photopic conditions. There were no morphological alterations of retinas at light microscopy. CONCLUSION: intravitreal injection of PS80 in the used concentration for intravitreal drug preparations do not cause any functional or morphological alterations of rabbit retinas. These results suggest that PS80 is not toxic to rabbit retinas and may be safely used in the preparation of new lipophilic drugs for intravitreal injection.
Assuntos
Polissorbatos/administração & dosagem , Retina/anatomia & histologia , Retina/fisiologia , Animais , Eletrorretinografia , Injeções Intravítreas , Coelhos , Retina/efeitos dos fármacosRESUMO
PURPOSE: To determine the half-life of mycophenolic acid (MPA) in the vitreous of New Zealand albino rabbits after intravitreal injection and the retinal toxicity of different doses of MPA. METHODS: Ten micrograms of MPA (Roche Bioscience, Palo Alto, CA) was injected in the vitreous of 16 rabbits, animals were sacrificed at different time-points, and vitreous samples underwent high-performance liquid chromatography. For functional and morphological studies, 5 doses of MPA (0.05, 0.5, 2, 10, and 100 µg) were injected in the vitreous of 20 rabbits. As control, contralateral eyes were injected with aqueous vehicle. Electroretinograms (ERGs) were recorded before injection and at days 7, 15, and 30. Animals were sacrificed on day 30 and retinas were analyzed under light microscopy. RESULTS: MPA half-life in the vitreous was 5.0±0.3 days. ERG revealed photoreceptor functional impairment in eyes injected with 0.5 µg and higher on day 30, while eyes injected with 100 µg presented the same changes already from day 15. No morphological change was found. CONCLUSIONS: MPA vitreous half-life is 5.0 days. Intravitreal injection of 0.5 µg MPA and higher causes dose- and time-related photoreceptor sensitivity decrease in rabbits. The MPA dose of 0.05 µg may be safe for intravitreal use in rabbits.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Imunossupressores/administração & dosagem , Ácido Micofenólico/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Fenômenos Eletrofisiológicos , Eletrorretinografia , Meia-Vida , Imunossupressores/farmacocinética , Imunossupressores/toxicidade , Injeções Intravítreas , Ácido Micofenólico/farmacocinética , Ácido Micofenólico/toxicidade , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Coelhos , Retina/efeitos dos fármacos , Retina/patologia , Fatores de Tempo , Corpo Vítreo/metabolismoRESUMO
Emerging treatments for dry age-related macular degeneration (AMD) and geographic atrophy focus on two strategies that target components involved in physiopathological pathways: prevention of photoreceptors and retinal pigment epithelium loss (neuroprotection induction, oxidative damage prevention, and visual cycle modification) and suppression of inflammation. Neuroprotective drugs, such as ciliary neurotrophic factor, brimonidine tartrate, tandospirone, and anti-amyloid ß antibodies, aim to prevent apoptosis of retinal cells. Oxidative stress and depletion of essential micronutrients are targeted by the Age-Related Eye Disease Study (AREDS) formulation. Visual cycle modulators reduce the activity of the photoreceptors and retinal accumulation of toxic fluorophores and lipofuscin. Eyes with dry age-related macular degeneration present chronic inflammation and potential treatments include corticosteroid and complement inhibition. We review the current concepts and rationale of dry age-related macular degeneration treatment that will most likely include a combination of drugs targeting different pathways involved in the development and progression of age-related macular degeneration.
Assuntos
Degeneração Macular/tratamento farmacológico , Animais , Ensaios Clínicos como Assunto , Via Alternativa do Complemento/efeitos dos fármacos , HumanosRESUMO
Ocular inflammation is one of the leading causes of blindness and loss of vision. Human uveitis is a complex and heterogeneous group of diseases characterized by inflammation of intraocular tissues. The eye may be the only organ involved, or uveitis may be part of a systemic disease. A significant number of cases are of unknown etiology and are labeled idiopathic. Animal models have been developed to the study of the physiopathogenesis of autoimmune uveitis due to the difficulty in obtaining human eye inflamed tissues for experiments. Most of those models are induced by injection of specific photoreceptors proteins (e.g., S-antigen, interphotoreceptor retinoid-binding protein, rhodopsin, recoverin, phosducin). Non-retinal antigens, including melanin-associated proteins and myelin basic protein, are also good inducers of uveitis in animals. Understanding the basic mechanisms and pathogenesis of autoimmune ocular diseases are essential for the development of new treatment approaches and therapeutic agents. The present review describes the main experimental models of autoimmune ocular inflammatory diseases.
Assuntos
Doenças Autoimunes , Modelos Animais de Doenças , Células Fotorreceptoras de Vertebrados/imunologia , Uveíte , Animais , Doenças Autoimunes/etiologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Doenças Autoimunes/fisiopatologia , Proteínas do Olho/imunologia , Fosfoproteínas/imunologia , Ratos , Uveíte/etiologia , Uveíte/imunologia , Uveíte/fisiopatologiaRESUMO
OBJECTIVES: Acute retinal necrosis is a rapidly progressive and devastating viral retinitis caused by the herpesvirus family. Systemic acyclovir is the treatment of choice; however, the progression of retinal lesions ceases approximately 2 days after treatment initiation. An intravitreal injection of acyclovir may be used an adjuvant therapy during the first 2 days of treatment when systemically administered acyclovir has not reached therapeutic levels in the retina. The aims of this study were to determine the pharmacokinetic profile of acyclovir in the rabbit vitreous after intravitreal injection and the functional effects of acyclovir in the rabbit retina. METHODS: Acyclovir (Acyclovir; Bedford Laboratories, Bedford, OH, USA) 1 mg in 0.1 mL was injected into the right eye vitreous of 32 New Zealand white rabbits, and 0.1 mL sterile saline solution was injected into the left eye as a control. The animals were sacrificed after 2, 9, 14, or 28 days. The eyes were enucleated, and the vitreous was removed. The half-life of acyclovir was determined using high-performance liquid chromatography. Electroretinograms were recorded on days 2, 9, 14, and 28 in the eight animals that were sacrificed 28 days after injection according to a modified protocol of the International Society for Clinical Electrophysiology of Vision. RESULTS: Acyclovir rapidly decayed in the vitreous within the first two days after treatment and remained at low levels from day 9 onward. The eyes that were injected with acyclovir did not present any electroretinographic changes compared with the control eyes. CONCLUSIONS: The vitreous half-life of acyclovir is short, and the electrophysiological findings suggest that the intravitreal delivery of 1 mg acyclovir is safe and well tolerated by the rabbit retina.
Assuntos
Aciclovir/farmacocinética , Antivirais/farmacocinética , Retina/efeitos dos fármacos , Corpo Vítreo/metabolismo , Animais , Modelos Animais de Doenças , Eletrorretinografia , Meia-Vida , Injeções Intravítreas , Coelhos , Retina/fisiologia , Fatores de TempoRESUMO
ABSTRACT Objective : to determine the functional and morphological effects at rabbits retina of PS80 concentration used in the preparation of intravitreal drugs. Methods: eleven New Zealand rabbits received a intravitreal injection of 0.1ml of PS80. As control, the contralateral eye of each rabbit received the same volume of saline. Electroretinography was performed according to a modified protocol, as well as biomicroscopy and retina mapping before injection and seven and ten days after. Animals were euthanized in the 30th day and the retinas were analyzed by light microscopy. Results: eyes injected with PS80 did not present clinical signs of intraocular inflammation. Electroretinography did not show any alteration of extent and implicit time of a and b waves at scotopic and photopic conditions. There were no morphological alterations of retinas at light microscopy. Conclusion: intravitreal injection of PS80 in the used concentration for intravitreal drug preparations do not cause any functional or morphological alterations of rabbit retinas. These results suggest that PS80 is not toxic to rabbit retinas and may be safely used in the preparation of new lipophilic drugs for intravitreal injection.
RESUMO Objetivo: determinar os efeitos funcionais e morfológicos na retina de coelhos da concentração de PS80 utilizada na preparação de drogas intravítreas. Métodos: onze coelhos New Zealand receberam injeção intravítrea de 0,1ml de PS80. Como controle, o olho contralateral de cada coelho recebeu o mesmo volume de soro fisiológico. Foram realizados eletrorretinogramas de acordo com o protocolo modificado, biomicroscopia e mapeamento de retina antes da injeção, sete e dez dias depois. Os animais foram sacrificados no 30o dia e as retinas analisadas por microscopia de luz. Resultados: os olhos injetados com PS80 não apresentaram sinais clínicos de inflamação intraocular. O eletrorretinograma não apresentou alteração de amplitude e tempo implícito das ondas a e b nas condições escotópica e fotópica. Não houve alteração morfológica da retina na microscopia de luz. Conclusão: a injeção intravítrea de PS80 na concentração utilizada na preparação de drogas intravítreas não causa alterações funcionais e morfológicas na retina de coelhos. Esses resultados sugerem que o PS80 não é tóxico para a retina de coelhos e pode ser usado com segurança na preparação de novas drogas lipofílicas para injeção intravítrea.
Assuntos
Animais , Polissorbatos/administração & dosagem , Retina/anatomia & histologia , Retina/fisiologia , Coelhos , Retina/efeitos dos fármacos , Eletrorretinografia , Injeções IntravítreasRESUMO
Vogt-Koyanagi-Harada disease (VKH), a well-established multiorgan disorder affecting pigmented structures, is an autoimmune disorder of melanocyte proteins in genetically susceptible individuals. Several clinical and experimental data point to the importance of the effector role of CD4+ T cells and Th1 cytokines, the relevance of searching a target protein in the melanocyte, and the relevance of the HLA-DRB1*0405 in the pathogenesis of the disease. Vogt-Koyanagi-Harada disease has a benign course when early diagnosed and adequately treated. Full-blown recurrences are rare after the acute stage of Vogt-Koyanagi-Harada disease is over. On the other hand, clinical findings, such as progressive tissue depigmentation (including sunset glow fundus) and uveitis recurrence, indicate that ocular inflammation may persist after the acute phase. Additionally, indocyanine green angiography findings suggest the presence of choroidal inflammation in eyes without clinically detectable inflammation. The aim of this paper is to review the latest research results on Vogt-Koyanagi-Harada disease pathogenesis and chronic/convalescent stages, which may help to better understand this potentially blinding disease and to improve its treatment.
Assuntos
Síndrome Uveomeningoencefálica , Doença Crônica , Antígenos HLA-DR/imunologia , Cadeias HLA-DRB1 , Humanos , Síndrome Uveomeningoencefálica/diagnóstico , Síndrome Uveomeningoencefálica/etiologiaRESUMO
OBJECTIVE: Wolfram syndrome (WS) is a rare, progressive, neurodegenerative disorder with an autosomal recessive pattern of inheritance. The gene for WS, WFS1, was identified on chromosome 4p16 and most WS patients carry mutations in this gene. However, some studies have provided evidence for genetic heterogeneity and the genotype-phenotype relationships are not clear. Our aim was to ascertain the spectrum of WFS1 mutations in Brazilian patients with WS and to examine the phenotype-genotype relationships in these patients. DESIGN AND METHODS: Clinical characterization and analyses of the WFS1 gene were performed in 27 Brazilian patients with WS from 19 families. RESULTS: We identified 15 different mutations in the WFS1 gene in 26 patients, among which nine are novel. All mutations occurred in exon 8, except for one missense mutation which was located in exon 5. Although we did not find any clear phenotype-genotype relationship in patients with mutations in exon 8, the homozygous missense mutation in exon 5 was associated with a mild phenotype: onset of diabetes mellitus and optic atrophy during adulthood with good metabolic control being achieved with low doses of sulfonylurea. CONCLUSIONS: Our data show that WFS1 is the major gene involved in WS in Brazilian patients and most mutations are concentrated in exon 8. Also, our study increases the spectrum of WFS1 mutations. Although no clear phenotype-genotype relationship was found for mutations in exon 8, a mild phenotype was associated with a homozygous missense mutation in exon 5.
Assuntos
Proteínas de Membrana/genética , Mutação de Sentido Incorreto , Síndrome de Wolfram/genética , Adolescente , Adulto , Brasil , Criança , Éxons/genética , Feminino , Genótipo , Homozigoto , Humanos , Masculino , Linhagem , Fenótipo , Adulto JovemRESUMO
PURPOSE: To report the incidence of orbital space-occupying lesions in an 11-year interval study of patients examined at the Hospital das Clínicas of FMUSP, and to evaluate which are the main specialties involved in the diagnosis and treatment of such conditions. METHODS: All cases of orbital space-occupying lesions in the period from 1993 to 2004 were revised. Of 924 obtained medical records, 155 were selected after histopathological analysis. Another 111 cases were gathered from the personal archives of a pathologist responsible for Ophthalmic Histopathology, from which 45 cases were excluded because they had already been included in the first source analysis. The data were analyzed and compared with the results from other institutions. RESULTS: Of the studied 181 orbital space-occupying lesions, 70% were primary, 23% secondary, 6% metastatic and lymphomas, and 1% was not classified. The most common specialties involved ophthalmologists in 72.37% of all 181 cases, head and neck surgeons in 14.36%, neurosurgeons in 6.62%, and others in 6.62%. CONCLUSIONS: The orbital mass lesions were treated mostly by an expert ophthalmologist. When other specialties were included, there was a modest increase in secondary tumor incidence when the final result was compared with previous studies on this subject. Our findings indicate that the creation of a trustworthy register of all orbital space-occupying lesions in Brazilian specialized services is necessary. The multidisciplinary character of the orbital mass lesions is corroborated by this review.
Assuntos
Medicina/estatística & dados numéricos , Neoplasias Orbitárias/patologia , Especialização , Adulto , Brasil/epidemiologia , Feminino , Hospitais Universitários , Humanos , Incidência , Masculino , Neoplasias Orbitárias/classificação , Neoplasias Orbitárias/epidemiologia , Neoplasias Orbitárias/cirurgia , Fatores de TempoRESUMO
PURPOSE: To assess the efficacy of intravitreal use of triamcinolone acetonide combined with laser photocoagulation for the treatment of diffuse diabetic macular edema and to compare it with the separate use of each treatment. METHODS: After systemic clinical control, thirty patients with diffuse diabetic macular edema were divided into 3 treatment groups: (1) macular grid photocoagulation; (2) intravitreal injection of 4 mg of triamcinolone acetonide; (3) combination of the two previous therapies. Follow-up was scheduled at predetermined intervals of one day, one week and monthly until completion of six months. The following parameters were analyzed: LogMAR best corrected visual acuity, central macular thickness, total macular volume and intraocular pressure. RESULTS: Grid photocoagulation did not significantly reduce the central macular thickness or the total macular volume. On the other hand, this reduction was statistically significant in the other two groups. All groups improved their mean visual acuity, however, the group that received both treatments had a higher percentage of patients that gained 10 or more letters. CONCLUSION: The simultaneous administration of grid photocoagulation with intravitreal triamcinolone can be considered an option for the treatment of diffuse diabetic macular edema.
Assuntos
Retinopatia Diabética , Glucocorticoides/uso terapêutico , Fotocoagulação a Laser , Edema Macular , Triancinolona Acetonida/uso terapêutico , Terapia Combinada/métodos , Interpretação Estatística de Dados , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/cirurgia , Feminino , Seguimentos , Humanos , Injeções , Pressão Intraocular/efeitos dos fármacos , Pressão Intraocular/fisiologia , Edema Macular/tratamento farmacológico , Edema Macular/fisiopatologia , Edema Macular/cirurgia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Acuidade Visual/efeitos dos fármacos , Acuidade Visual/fisiologia , Corpo VítreoRESUMO
Ocular inflammation is one of the leading causes of blindness and loss of vision. Human uveitis is a complex and heterogeneous group of diseases characterized by inflammation of intraocular tissues. The eye may be the only organ involved, or uveitis may be part of a systemic disease. A significant number of cases are of unknown etiology and are labeled idiopathic. Animal models have been developed to the study of the physiopathogenesis of autoimmune uveitis due to the difficulty in obtaining human eye inflamed tissues for experiments. Most of those models are induced by injection of specific photoreceptors proteins (e.g., S-antigen, interphotoreceptor retinoid-binding protein, rhodopsin, recoverin, phosducin). Non-retinal antigens, including melanin-associated proteins and myelin basic protein, are also good inducers of uveitis in animals. Understanding the basic mechanisms and pathogenesis of autoimmune ocular diseases are essential for the development of new treatment approaches and therapeutic agents. The present review describes the main experimental models of autoimmune ocular inflammatory diseases.
A inflamação ocular é uma das principais causas de perda visual e cegueira. As uveítes constituem um grupo complexo e heterogêneo de doenças caracterizadas por inflamação dos tecidos intraoculares. O olho pode ser o único órgão envolvido ou a uveíte pode ser parte de uma doença sistêmica. A etiologia é desconhecida em um número significativo de casos, que são considerados idiopáticos. Modelos animais têm sido desenvolvidos para estudar a fisiopatogênese da uveíte autoimune devido às dificuldades na obtenção de tecidos de olhos humanos inflamados para experimentos. Na maioria desses modelos, que simulam as uveítes autoimunes em humanos, a uveíte é induzida com proteínas específicas de fotorreceptores (antígeno-S, proteína ligadora de retinoide do interfotoreceptor, rodopsina, recoverina e fosducina). Antígenos não retinianos, como proteínas associadas à melanina e proteína básica de mielina, são também bons indutores de uveíte em animais. Entender os mecanismos básicos e a patogênese dessas doenças oculares é essencial para o desenvolvimento de novas formas de tratamento das uveítes autoimunes e de novos agentes terapêuticos. Nesta revisão serão abordados os principais modelos experimentais utilizados para o estudo de doenças inflamatórias oculares autoimunes.
Assuntos
Animais , Ratos , Doenças Autoimunes , Modelos Animais de Doenças , Células Fotorreceptoras de Vertebrados/imunologia , Uveíte , Doenças Autoimunes/etiologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Doenças Autoimunes/fisiopatologia , Proteínas do Olho/imunologia , Fosfoproteínas/imunologia , Uveíte/etiologia , Uveíte/imunologia , Uveíte/fisiopatologiaRESUMO
Emerging treatments for dry age-related macular degeneration (AMD) and geographi c atrophy focus on two strategies that target components involved in physiopathological pathways: prevention of photoreceptors and retinal pigment epithelium loss (neuroprotection induction, oxidative damage prevention, and visual cycle modification) and suppression of inflammation. Neuroprotective drugs, such as ciliary neurotrophic factor, brimonidine tartrate, tandospirone, and anti-amyloid β antibodies, aim to prevent apoptosis of retinal cells. Oxidative stress and depletion of essential micronutrients are targeted by the Age-Related Eye Disease Study (AREDS) formulation. Visual cycle modulators reduce the activity of the photoreceptors and retinal accumulation of toxic fluorophores and lipofuscin. Eyes with dry age-related macular degeneration present chronic inflammation and potential treatments include corticosteroid and complement inhibition. We review the current concepts and rationale of dry age-related macular degeneration treatment that will most likely include a combination of drugs targeting different pathways involved in the development and progression of age-related macular degeneration.
Os novos tratamentos para a forma seca da degeneração macular relacionada à idade (DMRI) e da atrofia geográfica têm sido baseados em duas estratégias que abordam componentes envolvidos nos mecanismos fisiopatológicos da doença: prevenção da perda de fotorreceptores e células do epitélio pigmentado da retina (indução de neuroproteção, diminuição do dano oxidativo e modificação do ciclo visual) e supressão da inflamação. As drogas neuroprotetoras visam evitar a apoptose das células retinianas, como o fator neurotrófico ciliar, o tartarato de brimonidina, a tandosporina e anticorpos antiamiloide β. A redução do dano oxidativo e a complementação de micronutrientes essenciais são os objetivos da fórmula AREDS. Os modificadores do ciclo visual reduzem a atividade dos fotorreceptores e o acúmulo de fluoróforos tóxicos e lipofuscina na retina. Olhos com a forma seca da degeneração macular relacionada à idade apresentam inflamação crônica e os novos tratamentos incluem corticosteroides e inibidores do sistema complemento. Neste artigo, revisamos o estágio atual do tratamento da forma seca da degeneração macular relacionada à idade que provavelmente será feito através da combinação de drogas que agem em diferentes componentes envolvidos no aparecimento e na progressão da degeneração macular relacionada à idade.
Assuntos
Animais , Humanos , Degeneração Macular/tratamento farmacológico , Ensaios Clínicos como Assunto , Via Alternativa do Complemento/efeitos dos fármacosRESUMO
OBJECTIVES: Acute retinal necrosis is a rapidly progressive and devastating viral retinitis caused by the herpesvirus family. Systemic acyclovir is the treatment of choice; however, the progression of retinal lesions ceases approximately 2 days after treatment initiation. An intravitreal injection of acyclovir may be used an adjuvant therapy during the first 2 days of treatment when systemically administered acyclovir has not reached therapeutic levels in the retina. The aims of this study were to determine the pharmacokinetic profile of acyclovir in the rabbit vitreous after intravitreal injection and the functional effects of acyclovir in the rabbit retina. METHODS: Acyclovir (Acyclovir; Bedford Laboratories, Bedford, OH, USA) 1 mg in 0.1 mL was injected into the right eye vitreous of 32 New Zealand white rabbits, and 0.1 mL sterile saline solution was injected into the left eye as a control. The animals were sacrificed after 2, 9, 14, or 28 days. The eyes were enucleated, and the vitreous was removed. The half-life of acyclovir was determined using high-performance liquid chromatography. Electroretinograms were recorded on days 2, 9, 14, and 28 in the eight animals that were sacrificed 28 days after injection according to a modified protocol of the International Society for Clinical Electrophysiology of Vision. RESULTS: Acyclovir rapidly decayed in the vitreous within the first two days after treatment and remained at low levels from day 9 onward. The eyes that were injected with acyclovir did not present any electroretinographic changes compared with the control eyes. CONCLUSIONS: The vitreous half-life of acyclovir is short, and the electrophysiological findings suggest that the intravitreal delivery of 1 mg acyclovir is safe and well tolerated by the rabbit retina.
Assuntos
Animais , Coelhos , Aciclovir/farmacocinética , Antivirais/farmacocinética , Retina/efeitos dos fármacos , Corpo Vítreo/metabolismo , Modelos Animais de Doenças , Eletrorretinografia , Meia-Vida , Injeções Intravítreas , Retina/fisiologia , Fatores de TempoRESUMO
Vogt-Koyanagi-Harada disease (VKH), a well-established multiorgan disorder affecting pigmented structures, is an autoimmune disorder of melanocyte proteins in genetically susceptible individuals. Several clinical and experimental data point to the importance of the effector role of CD4+ T cells and Th1 cytokines, the relevance of searching a target protein in the melanocyte, and the relevance of the HLA-DRB1*0405 in the pathogenesis of the disease. Vogt-Koyanagi-Harada disease has a benign course when early diagnosed and adequatey treated. Full-blown recurrences are rare after the acute stage of Vogt-Koyanagi-Harada disease is over. On the other hand, clinical findings, such as progressive tissue depigmentation (including sunset glow fundus) and uveitis recurrence, indicate that ocular inflammation may persist after the acute phase. Additionally, indocyanine green angiography findings suggest the presence of choroidal inflammation in eyes without clinically detectable inflammation. The aim of this paper is to review the latest research results on Vogt-Koyanagi-Harada disease pathogenesis and chronic/convalescent stages, which may help to better understand this potentially blinding disease and to improve its treatment.
A doença de Vogt-Koyanagi-Harada (VKH) afeta vários órgãos que têm em comum a presença de pigmento. É doença autoimune que agride os melanócitos de indivíduos geneticamente susceptíveis. Inúmeras evidências clínicas e experimentais demonstram a importância de células T CD4+ como células efetoras da resposta imune celular, das citocinas pró-inflamatórias Th1, da procura da proteína-alvo dentro do melanócito, e da relevância do HLA-classe II DRB1*0405 na patogênese desta doença. A doença de Vogt-Koyanagi-Harada apresenta bom prognóstico visual desde que o diagnóstico seja precoce e o tratamento instituído seja adequado. Recidivas com acometimento do segmento posterior são raras após a fase aguda da doença. No entanto, achados clínicos como a progressiva despigmentação do fundo, incluindo o aspecto em por do sol, e as recidivas da uveíte indicam que a inflamação ocular pode persistir mesmo após a fase aguda da doença. Os achados da angiografia com indocianina verde também sugerem a presença de inflamação da coróide mesmo em olhos sem inflamação clinicamente detectável. O objetivo do presente trabalho é rever os mais recentes estudos sobre a patogênese da doença Vogt-Koyanagi-Harada e sobre os aspectos clínicos da fase crônica e/ou convalescente da doença, permitindo melhores conhecimentos sobre esta doença potencialmente mórbida e oferecendo terapias mais adequadas.
Assuntos
Humanos , Síndrome Uveomeningoencefálica , Doença Crônica , Antígenos HLA-DR/imunologia , Síndrome Uveomeningoencefálica/diagnóstico , Síndrome Uveomeningoencefálica/etiologiaRESUMO
OBJETIVO: Avaliar a eficácia do uso intravítreo da triancinolona acetonida associada a fotocoagulação com laser no tratamento do edema macular difuso diabético. Comparar esta associação terapêutica com o uso isolado de cada tratamento. MÉTODOS: Após controle clínico sistêmico, trinta pacientes portadores de edema macular difuso diabético foram divididos em 3 grupos de tratamento: (1) fotocoagulação macular em grade com laser de argônio; (2) aplicação intravítrea de 4 mg de triancinolona acetonida; (3) associação dos itens anteriores. O seguimento foi realizado em intervalos predeterminados de um dia, uma semana e mensalmente, até completar 6 meses. Foram analisados os parâmetros: acuidade visual corrigida LogMAR, espessura macular central, volume macular total e pressão intra-ocular. RESULTADOS: A fotocoagulação com laser não reduziu de forma estatisticamente significativa a espessura macular central e o volume macular total. Esta redução foi significativa e estatisticamente semelhante nos outros dois grupos. Todos os grupos apresentaram melhora da acuidade visual, entretanto, o grupo que recebeu a associação do laser com a triancinolona intravítrea obteve maior porcentagem de pacientes com ganho de 10 ou mais letras de visão. CONCLUSÃO: O uso simultâneo da fotocoagulação com a triancinolona intravítrea pode ser considerado uma opção terapêutica para o edema macular difuso diabético.
PURPOSE: To assess the efficacy of intravitreal use of triamcinolone acetonide combined with laser photocoagulation for the treatment of diffuse diabetic macular edema and to compare it with the separate use of each treatment. METHODS: After systemic clinical control, thirty patients with diffuse diabetic macular edema were divided into 3 treatment groups: (1) macular grid photocoagulation; (2) intravitreal injection of 4 mg of triamcinolone acetonide; (3) combination of the two previous therapies. Follow-up was scheduled at predetermined intervals of one day, one week and monthly until completion of six months. The following parameters were analyzed: LogMAR best corrected visual acuity, central macular thickness, total macular volume and intraocular pressure. RESULTS: Grid photocoagulation did not significantly reduce the central macular thickness or the total macular volume. On the other hand, this reduction was statistically significant in the other two groups. All groups improved their mean visual acuity, however, the group that received both treatments had a higher percentage of patients that gained 10 or more letters. CONCLUSION: The simultaneous administration of grid photocoagulation with intravitreal triamcinolone can be considered an option for the treatment of diffuse diabetic macular edema.
Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Retinopatia Diabética , Glucocorticoides/uso terapêutico , Fotocoagulação a Laser , Edema Macular , Triancinolona Acetonida/uso terapêutico , Terapia Combinada/métodos , Interpretação Estatística de Dados , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/cirurgia , Seguimentos , Injeções , Pressão Intraocular/efeitos dos fármacos , Pressão Intraocular/fisiologia , Edema Macular/tratamento farmacológico , Edema Macular/fisiopatologia , Edema Macular/cirurgia , Resultado do Tratamento , Corpo Vítreo , Acuidade Visual/efeitos dos fármacos , Acuidade Visual/fisiologiaRESUMO
OBJETIVO: Estudar a incidência das lesões expansivas orbitárias submetidas à biópsia em uma casuística de 11 anos no Hospital das Clínicas da FMUSP, e avaliar quais as principais especialidades envolvidas no diagnóstico e no tratamento de tais afecções. CASUÍSTICA E MÉTODOS: Solicitou-se ao setor de arquivos do hospital todos os casos de tumores e lesões de órbita submetidas à biópsia no período de 1993 a 2004. Dos 924 prontuários obtidos, 115 foram separados após análise dos dados segundo os resultados histopatológicos obtidos. Outros 111 pacientes foram obtidos por meio dos arquivos pessoais da patologista encarregada da Oftalmologia no Departamento de Patologia, dos quais 45 pacientes foram excluídos por coincidirem com a fonte anterior. Os dados foram contabilizados e comparados com os de outros serviços. RESULTADOS: Das 181 lesões orbitárias estudadas, 70 por cento eram primárias, 23 por cento eram secundárias, 6 por cento consistiam de metástases e linfomas e 1 por cento não foi classificada. Em relação à especialidade responsável diretamente pelo paciente, 72,37 por cento dos pacientes foram assistidos por oftalmologistas, 14,36 por cento por cirurgiões de cabeça e pescoço, 6,62 por cento por neurocirurgiões e 6,62 por cento por outros setores do hospital. CONCLUSÕES: As afecções orbitárias são atendidas em sua maioria pelos oftalmologistas especializados em tal área, e ao se incluir nesta casuística outras especialidades, nota-se um aumento no número de casos de lesões tumorais secundárias quando comparada ao de outros trabalhos realizados em serviços no exterior. Há necessidade de criar-se um registro confiável dos casos de lesões expansivas orbitárias nos serviços especializados brasileiros, e confirma-se o caráter multidisciplinar do objeto deste estudo.
PURPOSE: To report the incidence of orbital space-occupying lesions in an 11-year interval study of patients examined at the Hospital das Clínicas of FMUSP, and to evaluate which are the main specialties involved in the diagnosis and treatment of such conditions. METHODS: All cases of orbital space-occupying lesions in the period from 1993 to 2004 were revised. Of 924 obtained medical records, 155 were selected after histopathological analysis. Another 111 cases were gathered from the personal archives of a pathologist responsible for Ophthalmic Histopathology, from which 45 cases were excluded because they had already been included in the first source analysis. The data were analyzed and compared with the results from other institutions. RESULTS: Of the studied 181 orbital space-occupying lesions, 70 percent were primary, 23 percent secondary, 6 percent metastatic and lymphomas, and 1 percent was not classified. The most common specialties involved ophthalmologists in 72.37 percent of all 181 cases, head and neck surgeons in 14.36 percent, neurosurgeons in 6.62 percent, and others in 6.62 percent. CONCLUSIONS: The orbital mass lesions were treated mostly by an expert ophthalmologist. When other specialties were included, there was a modest increase in secondary tumor incidence when the final result was compared with previous studies on this subject. Our findings indicate that the creation of a trustworthy register of all orbital space-occupying lesions in Brazilian specialized services is necessary. The multidisciplinary character of the orbital mass lesions is corroborated by this review.
Assuntos
Adulto , Feminino , Humanos , Masculino , Neoplasias Orbitárias/patologia , Medicina/estatística & dados numéricos , Brasil/epidemiologia , Hospitais Universitários , Incidência , Neoplasias Orbitárias/classificação , Neoplasias Orbitárias/epidemiologia , Neoplasias Orbitárias/cirurgia , Fatores de TempoRESUMO
O diagnóstico da retinosquise pode ser, muitas vezes, difícil por causa das formas clínicas atípicas. Freqüentemente, os exames complementares são necessários para a confirmação diagnóstica. O descolamento de retina deve sempre ser considerado no diagnóstico diferencial. Relato de caso: Paciente do sexo feminino, negra, com 61 anos de idade, assintomática. Na fundoscopia do olho direito, detectou-se uma lesão retiniana superior periférica que se estendia ao pólo posterior. O olho contralateral era normal. Na ultra-sonografia do olho direito, evidenciou-se uma membrana de alta reflexividade. No campo visual, detectou-se um defeito absoluto no campo inferior. O OCT, com scan centrado na ruptura da camada externa, demonstrou a separação da estrutura da retina. O ERG escotópico revelou uma nítida redução da amplitude da onda b no olho direito em relação ao olho contralateral (resposta com "onda negativa" no olho direito). O ERG multifocal era sem alterações nos dois olhos. Nos casos duvidosos, os exames complementares são indispensáveis. O OCT demonstrou morfologicamente a alteração. O ERG e a presença do escotoma absoluto no campo inferior confirmaram a alteração funcional da retina. A presença da "onda negativa" demonstra o comprometimento da função das camadas internas da retina através da redução da onda b e a função normal dos fotorreceptores com a presença da onda a inalterada. Casos duvidosos devem sempre ser investigados e estudados cuidadosamente para que tenhamos um diagnóstico de certeza e, conseqüentemente, uma conduta médica mais efetiva evitando procedimentos que possam eventualmente comprometer a visão.
Retinoschisis diagnosis can be very difficult in atypical forms. Special exams are necessary to differentiate retinoschisis from other pathologies such as retinal detachment. Case Report: A 61-year-old black woman presented for routine examination. Fundus of the right eye reveled a superior periphery lesion extending to the posterior pole. The ultrassonography of the same eye showed a high reflective membrane. An inferior field absolute scotoma was detected. The OCT scan that was positioned at lesion in the outer retinal break demonstrated the fragmentation of the retinal layer. The scotopic ERG showed a reduction of the b wave amplitude of the right eye compared to the left eye (Negative electroretinogram). The multifocal ERG was normal in both eyes. The OCT demonstrated to be an useful toll to detect morphological alterations. The ERG and the absolute scotoma in the inferior field, demonstrated the retinal functional defect. A negative electroretinogram, showed a normal a wave and a reduced b wave demonstrating that the photoreceptor inner segments were relatively intact and that the initial damage in this disorder would seem to occur in the inner retinal layers. In doubtful cases especial exams are necessary and a careful investigation must confirm the diagnosis. The indications for treatment should be seriously analysed to avoid any intervention that can be harmful for the patient's prognosis.