RESUMO
The objective of the present study was to develop a quantitative method to evaluate laser-induced choroidal neovascularization (CNV) in a rat model using Heidelberg Retina Angiograph 2 (HRA2) imaging. The expression of two heparan sulfate proteoglycans (HSPG) related to inflammation and angiogenesis was also investigated. CNV lesions were induced with argon laser in 21 heterozygous Zucker rats and after three weeks a fluorescein angiogram and autofluorescence exams were performed using HRA2. The area and greatest linear dimension were measured by two observers not aware of the protocol. Bland-Altman plots showed agreement between the observers, suggesting that the technique was reproducible. After fluorescein angiogram, HSPG (perlecan and syndecan-4) were analyzed by real-time RT-PCR and immunohistochemistry. There was a significant increase in the expression of perlecan and syndecan-4 (P < 0.0001) in retinas bearing CNV lesions compared to control retinas. The expression of these two HSPG increased with increasing CNV area. Immunohistochemistry demonstrated that the rat retina damaged with laser shots presented increased expression of perlecan and syndecan-4. Moreover, we observed that the overexpression occurred in the outer layer of the retina, which is related to choroidal damage. It was possible to develop a standardized quantitative method to evaluate CNV in a rat model using HRA2. In addition, we presented data indicating that the expression of HSPG parallels the area of CNV lesion. The understanding of these events offers opportunities for studies of new therapeutic interventions targeting these HSPG.
Assuntos
Animais , Feminino , Ratos , Neovascularização de Coroide/metabolismo , Proteoglicanas de Heparan Sulfato/metabolismo , /análise , Neovascularização de Coroide/etiologia , Neovascularização de Coroide/patologia , Angiofluoresceinografia/métodos , Proteoglicanas de Heparan Sulfato/análise , Imuno-Histoquímica , Fotocoagulação a Laser , Oftalmoscopia/métodos , Ratos Zucker , Reação em Cadeia da Polimerase Via Transcriptase Reversa , /metabolismoRESUMO
The objective of the present study was to develop a quantitative method to evaluate laser-induced choroidal neovascularization (CNV) in a rat model using Heidelberg Retina Angiograph 2 (HRA2) imaging. The expression of two heparan sulfate proteoglycans (HSPG) related to inflammation and angiogenesis was also investigated. CNV lesions were induced with argon laser in 21 heterozygous Zucker rats and after three weeks a fluorescein angiogram and autofluorescence exams were performed using HRA2. The area and greatest linear dimension were measured by two observers not aware of the protocol. Bland-Altman plots showed agreement between the observers, suggesting that the technique was reproducible. After fluorescein angiogram, HSPG (perlecan and syndecan-4) were analyzed by real-time RT-PCR and immunohistochemistry. There was a significant increase in the expression of perlecan and syndecan-4 (P < 0.0001) in retinas bearing CNV lesions compared to control retinas. The expression of these two HSPG increased with increasing CNV area. Immunohistochemistry demonstrated that the rat retina damaged with laser shots presented increased expression of perlecan and syndecan-4. Moreover, we observed that the overexpression occurred in the outer layer of the retina, which is related to choroidal damage. It was possible to develop a standardized quantitative method to evaluate CNV in a rat model using HRA2. In addition, we presented data indicating that the expression of HSPG parallels the area of CNV lesion. The understanding of these events offers opportunities for studies of new therapeutic interventions targeting these HSPG.
Assuntos
Neovascularização de Coroide/metabolismo , Proteoglicanas de Heparan Sulfato/metabolismo , Sindecana-4/análise , Animais , Neovascularização de Coroide/etiologia , Neovascularização de Coroide/patologia , Feminino , Angiofluoresceinografia/métodos , Proteoglicanas de Heparan Sulfato/análise , Imuno-Histoquímica , Fotocoagulação a Laser , Oftalmoscopia/métodos , Ratos , Ratos Zucker , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sindecana-4/metabolismoRESUMO
BACKGROUND: Choroidal neovascularization (CNV) is the main cause of severe visual loss in age-related macular degeneration (AMD). Heparin/heparan sulfate are known to play important roles in neovascularization due to their abilities to bind and modulate angiogenic growth factors and cytokines. Previously, we have isolated from marine shrimp a heparin-like compound with striking anti-inflammatory action and negligible anticoagulant and hemorrhagic activities. OBJECTIVES: To investigate the role of this novel heparin-like compound in angiogenic processes. METHODS AND RESULTS: The anti-angiogenic effect of this heparinoid in laser-induced CNV and in vitro models is reported. The compound binds to growth factors (FGF-2, EGF and VEGF), blocks endothelial cell proliferation and shows no cytotoxic effect. The decrease in proliferation is not related to cell death either by apoptosis or secondary necrosis. The results also showed that the heparinoid modified the 2-D network organization in capillary-like structures of endothelial cells in Matrigel and reduced the CNV area. The effect on CNV area correlates with decreases in the levels of VEGF and TGF-ß1 in the choroidal tissue. The low content of 2-O-sulfate groups in this heparinoid may explain its potent anti-angiogenic effect. CONCLUSIONS: The properties of the shrimp heparinoid, such as potent anti-angiogenic and anti-inflammatory activities but insignificant anticoagulant or hemorrhagic actions, point to this compound as a compelling drug candidate for treating neovascular AMD and other angioproliferative diseases. A mechanism for the anti-angiogenic effect of the heparinoid is proposed.
Assuntos
Heparina/química , Animais , Proliferação de Células , Sobrevivência Celular , Neovascularização de Coroide , Colágeno/química , Combinação de Medicamentos , Células Endoteliais/citologia , Feminino , Glicosaminoglicanos/química , Heterozigoto , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Laminina/química , Neovascularização Patológica , Penaeidae , Proteoglicanas/química , Ratos , Ratos ZuckerRESUMO
BACKGROUND/AIMS: This study evaluated the short-term safety and feasibility of epiretinal strontium-90 brachytherapy delivered concomitantly with intravitreal bevacizumab for the treatment of subfoveal CNV due to AMD for 12 months. A 3-year follow-up is planned. METHODS: In this prospective, non-randomised, multicentre study, 34 treatment-naïve patients with predominantly classic, minimally classic and occult subfoveal CNV lesions received a single treatment with 24 Gy beta radiation (strontium-90) and two injections of the anti-VEGF antibody bevacizumab. Adverse events were observed. BCVA was measured using standard ETDRS vision charts. RESULTS: Twelve months after treatment, no radiation-associated adverse events were observed. In the intent-to-treat (ITT) population, 91% of patients lost <3 lines (15 ETDRS letters) of vision at 12 months, 68% improved or maintained their BCVA at 12 months, and 38% gained >/=3 lines. The mean change in BCVA observed at month 12 was a gain of 8.9 letters. CONCLUSION: The safety and efficacy of intraocular, epiretinal brachytherapy delivered concomitantly with anti-VEGF therapy for the treatment of subfoveal CNV secondary to AMD were promising in this small study population. Long-term safety will be assessed for 3 years. This regimen is being evaluated in a large, multicentre, phase III study.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Neovascularização de Coroide/radioterapia , Degeneração Macular/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos de Estrôncio/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados , Bevacizumab , Braquiterapia/métodos , Neovascularização de Coroide/complicações , Neovascularização de Coroide/tratamento farmacológico , Terapia Combinada , Feminino , Humanos , Degeneração Macular/complicações , Degeneração Macular/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Segurança , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade VisualRESUMO
BACKGROUND: This in vivo study assessed and compared the effectiveness of an aqueous indocyanine green (ICG) formulation (R-ICG) and a lipid ICG formulation (L-ICG) in occluding the rabbit choriocapillaris, and determined the singlet oxygen quantum yields and aggregation properties of both formulations in vitro. METHODS: Singlet oxygen production and aggregation were compared. The eye fundus of 30 albino rabbits was irradiated 0-15 min after dye injection using an 810 nm diode laser. Fluorescein angiography and light microscopy were used to evaluate the safety and efficacy of R-ICG and L-ICG. RESULTS: L-ICG decreased the dimerisation constant and the tendency of ICG to form aggregates, and increased the efficiency of ICG in generating singlet oxygen (R-ICG, PhiDelta = 0.120 and L-ICG, PhiDelta = 0.210). Using a 10 mg/kg dose, choriocapillaris occlusion was achieved at a light dose of 35.8 J/cm(2) with L-ICG and 71.6 J/cm(2) with R-ICG with minimal damage to the neurosensory retina. CONCLUSION: Restrictions to the use of ICG in aqueous solution, low singlet oxygen quantum yields and high aggregation tendency, were overcome with L-ICG. The lower laser irradiance required to obtain choriocapillaris occlusion may suggest that L-ICG is a more potent and selective photosensitiser than R-ICG.
Assuntos
Corioide/irrigação sanguínea , Verde de Indocianina/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Capilares/efeitos dos fármacos , Capilares/efeitos da radiação , Química Farmacêutica , Lasers , Óptica e Fotônica , Oxigênio/química , Fotoquímica , CoelhosRESUMO
PURPOSE: The objective of this paper is to describe the optical coherence tomography (OCT) characteristics of patients with full-thickness traumatic macular hole (TMH) and to correlate them with biomicroscopy findings. METHODS: Twelve eyes of ten consecutive patients with full-thickness TMH participated in this observational retrospective multicentre study. Patients underwent biomicroscopic fundus examination, colour fundus photography, and OCT. RESULTS: Traumatic macular hole was documented with OCT in five women and five men. Mean (range) time between trauma and macular hole (MH) diagnosis was 8.1 (1-24) months. The shape of TMHs was round in 11 (91.7%) eyes. The posterior vitreous was completely detached in six (50%) eyes, and with an operculum in one (8.3%) eye. The common findings seen on OCT were: (1) full-thickness loss of retinal tissue through the hole with sharp edges, perpendicular to the retinal pigment epithelium in five (41.7%) eyes; (2) TMH with an operculum totally detached from the hole's edge in two (16.7%) eyes; (3) presence of epiretinal membrane around of the hole in three (25%) eyes; and (4) presence of abnormalities of the surrounding retina in all (100%) eyes. The OCT characteristics correlated well with biomicroscopic findings, and these characteristics may be predictive for final visual acuity (VA) in TMHs. Only one of the TMHs closed spontaneously in our series. CONCLUSION: Optical coherence tomography complements biomicroscopy in the evaluation of full-thickness TMHs.
Assuntos
Ferimentos Oculares Penetrantes/diagnóstico , Perfurações Retinianas/diagnóstico , Descolamento do Vítreo/diagnóstico , Adolescente , Adulto , Criança , Membrana Epirretiniana/cirurgia , Ferimentos Oculares Penetrantes/cirurgia , Feminino , Fundo de Olho , Humanos , Macula Lutea/cirurgia , Masculino , Microscopia Acústica , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Perfurações Retinianas/cirurgia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Acuidade Visual/fisiologia , Descolamento do Vítreo/cirurgia , Adulto JovemRESUMO
PURPOSE: To report two cases of acute endophthalmitis following intravitreal bevacizumab injection. METHODS: Two patients with exudative age-related macular degeneration were treated sequentially with an intravitreal injection of bevacizumab and developed signs of severe but painless infectious endophthalmitis 2 days later. Vitreous samples were obtained, followed by the injection of vancomycin 1 mg/0.1 ml and ceftazidime 2.25 mg/0.1 ml. Pulsed-field gel electrophoresis (PFGE) was used to determine whether the isolated microorganisms were the same. RESULTS: Coagulase-negative staphylococci were identified and isolated from the vitreous specimen of both patients. PFGE revealed different patterns of banding, excluding that interpatient contamination occured. CONCLUSIONS: Infectious endophthalmitis is a potential complication of intravitreal bevacizumab injection.
Assuntos
Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Endoftalmite/induzido quimicamente , Infecções Estafilocócicas/induzido quimicamente , Doença Aguda , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Bevacizumab , Endoftalmite/microbiologia , Feminino , Humanos , Injeções/métodos , Degeneração Macular/tratamento farmacológico , Masculino , Infecções Estafilocócicas/microbiologia , Corpo Vítreo/microbiologiaRESUMO
Das doenças sistêmicas com alterações oculares, destacam-se a retinopatia diabética e a oftalmopatia de Graves que têm em comum vários aspectos: são alterações endócrinas e metabólicas, auto-imunes e o acometimento ocular pode ser grave, levando à perda da função visual. A orientação correta do médico generalista pode modificar o prognóstico visual dos portadores destas doenças, pois dá oportunidade para que o oftalmologista intervenha no momento adequado.No diabetes a principal alteração ocular ocorre na retina, com o desenvolvimento da retinopatia diabética que se manifesta em 30% dos casos.Na oftalmopatia de Graves é importante o esclarecimento de que nem sempre as alterações oculares estão relacionadas a alterações hormonais que possam sinalizar a atividade da doença. A doença ocular pode ocorrer no hipertireoidismo, bem como no hipotireoidismo; em pacientes sem alterações hormonais afeta principalmente os tecidos adiposo e muscular da órbita e do olho. Descreve-se neste artigo o tratamento atual da retinopatia diabética e da oftalmopatia de Graves para que os pacientes possam ser orientados e esclarecidos sobre as condutas a serem adotadas pelo oftalmologista.
RESUMO
AIMS: To study the effectiveness of indocyanine green mediated photothrombosis in the management of predominantly classic subfoveal choroidal neovascularisation associated with age related macular degeneration. METHODS: Prospective, non-comparative, interventional case series of nine patients with predominantly classic subfoveal choroidal neovascularisation secondary to age related macular degeneration who declined photocoagulation or verteporfin photodynamic therapy. Patients were submitted to one or more treatments with an intravenous injection of a small volume of high concentration indocyanine green solution followed by low irradiance, large spot 810 nm continuous laser application via a transpupillary approach. Main outcome measures were change in best corrected visual acuity and macular exudative manifestations. RESULTS: After 12 months of follow up, the final best corrected visual acuity was the same (plus or minus two ETDRS lines) in five eyes (55%), improved more than two ETDRS lines in three eyes (33%), and worsened by more than two lines in the remaining eye. The improved vision was probably related to partial or complete restoration of the macular architecture as a result of fluid resolution, whereas the worsened vision was primarily the result of treatment failure in achieving substantial choroidal neovascular occlusion. There were no complications related to the procedure. CONCLUSION: Indocyanine green mediated photothrombosis may be an effective alternative treatment for predominantly classic subfoveal choroidal neovascularisation caused by age related macular degeneration.
Assuntos
Neovascularização de Coroide/cirurgia , Verde de Indocianina/uso terapêutico , Fotocoagulação , Degeneração Macular/complicações , Fármacos Fotossensibilizantes/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/etiologia , Terapia Combinada/métodos , Feminino , Angiofluoresceinografia , Humanos , Degeneração Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Acuidade Visual/fisiologiaRESUMO
OBJECTIVE: To study the aerobic conjunctival flora of diabetic patients and its relation to the presence and level of diabetic retinopathy and the duration of the disease. METHODS: One hundred three patients from the diabetic retinopathy screening program of the Federal University of São Paulo with no evidence of ocular surface disease were included. The diabetic patient cohort was compared with 60 nondiabetic subjects. All patients underwent slit-lamp evaluation, conjunctival scrapings, and indirect ophthalmoscopy. RESULTS: The frequency of positive conjunctival cultures was significantly higher in the diabetic group (94.18%) than in the nondiabetic group (73.33%). Among diabetic patients, a significantly higher frequency of positive cultures was detected in those with diabetic retinopathy than in those without retinopathy. Neither the duration of the diabetes nor the hypoglycemic therapy correlated with the culture results. Coagulase-negative Staphylococcus was the most common microorganism isolated, and its identification was more frequent in patients with retinopathy than in those without diabetic retinopathy. CONCLUSION: Diabetic patients have a significantly higher number of positive conjunctival cultures. The presence of diabetic retinopathy was correlated with an increase in positive cultures and a higher proportion of coagulase-negative Staphylococcus.