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1.
Medicine (Baltimore) ; 99(7): e19007, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049795

RESUMO

Conbercept is a novel anti-vascular endothelial growth factor for the treatment of age-related macular degeneration (AMD). The most optimal injection strategy is unknown. To assess the effectiveness of intravitreal injection of conbercept using the 3 + pro re nata (PRN) and 3 + Q3 M strategies for the treatment of exudative AMD.From January 2015 to January 2018, patients confirmed with exudative AMD at Qilu Hospital of Shandong University were included in this retrospective study. Intravitreal injection of 0.5 mg of conbercept was conducted either with the 3 + PRN or 3 + Q3 M strategy. Best-corrected visual acuity (BCVA), intraocular pressure, and optical coherence tomography were conducted at 1 and 2 weeks, then every month. fundus fluorescein angiography examination was conducted every 3 months.There were 106 eyes from 106 patients. The number of follow-ups (3 + Q3 M: 12.4 ±â€Š1.3 vs 3 + PRN: 12.9 ±â€Š1.6, P = .079) and the follow-up time (3 + Q3 M: 12.7 ±â€Š0.6 vs 3 + PRN: 12.5 ±â€Š0.7 months, P = .121) were similar in the 2 groups. The number of injections was less in 3 + PRN than 3 + Q3 M (5.3 ±â€Š1.0 vs 6.0 ±â€Š0.0, P < .001) The BCVA at months 7 and 9 to 12 in the 3 + Q3 M (n = 51) group were lower than for 3 + PRN (n = 55) (all P < .05). The CRT at months 9 to 12 in the 3 + Q3 M group was lower than in the 3 + PRN group (all P < .05). There were no differences between the 2 groups regarding the exudation area during follow-up. No serious treatment-related ocular complications or serious systemic adverse events were found.The 3 + PRN and 3 + Q3 M strategies of intravitreal injection of conbercept are effective in treating exudative AMD. The 3 + Q3 M strategy needs more injection but is more effective in increasing visual acuity and reducing macular CRT than the 3 + PRN strategy.


Assuntos
Degeneração Macular/tratamento farmacológico , Proteínas Recombinantes de Fusão/administração & dosagem , Idoso , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Degeneração Macular/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes de Fusão/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
2.
Klin Monbl Augenheilkd ; 237(1): 79-84, 2020 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-30736075

RESUMO

PURPOSE: Diabetic retinopathy is one of the worst complications of diabetes and can threaten sight. The aim of our study is to compare the clinical outcomes and ultrastructural changes in diabetic retinopathy patients after intravitreal admission of either ranibizumab (Lucentis) or aflibercept (Eylea). METHODS: In our prospective study, 27 patients with PDR were enrolled. They were divided into two groups - 14 PDR patients treated with ranibizumab and 13 PDR patients treated with aflibercept. In both groups, a complete ophthalmological examination was performed, including OCT. In 12 patients (6 from each group), pars plana vitrectomy was performed with excision of epiretinal membranes. Transmission and scanning electron microscopy of the membranes was performed. RESULTS: Clinical findings - in both groups there was a decrease in the neovascular proliferation and macular oedema. CRT was reduced with approximately 100 - 120мk. In the Eylea group, there was general shrinking of neovascular proliferation with lower risk of bleeding. The ultrastructural analysis showed more significant reduction in endothelial fenestration after Eylea application, with clustering of platelets and erythrocytes in the capillary lumen. Increased numbers of macrophages were found in the membranes of both groups. CONCLUSION: Our results show that aflibercept is very effective in treating PDR. It causes more significant reduction of endothelial fenestration and more evident thrombotic microangiopathy than other anti-VEGF drugs, and thus diminishes macular oedema and prevents neovascular tissue from bleeding. Eylea inhibits both VEGF and placental growth factor and thus modifies the whole pathophysiology of DR. It is therefore more effective than other treatment medications.


Assuntos
Inibidores da Angiogênese , Retinopatia Diabética , Ranibizumab , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão , Inibidores da Angiogênese/administração & dosagem , Retinopatia Diabética/tratamento farmacológico , Humanos , Injeções Intravítreas , Estudos Prospectivos , Ranibizumab/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Fator A de Crescimento do Endotélio Vascular
3.
J Surg Res ; 245: 273-280, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31421373

RESUMO

BACKGROUND: Transplantation of lungs procured after donation after circulatory death (DCD) is challenging because postmortem metabolic degradation may engender susceptibility to ischemia-reperfusion (IR) injury. Because oxidative mitochondrial DNA (mtDNA) damage has been linked to endothelial barrier disruption in other models of IR injury, here we used a fusion protein construct targeting the DNA repair 8-oxoguanine DNA glycosylase-1 (OGG1) to mitochondria (mtOGG1) to determine if enhanced repair of mtDNA damage attenuates endothelial barrier dysfunction after IR injury in a rat model of lung procurement after DCD. MATERIALS AND METHODS: Lungs excised from donor rats 1 h after cardiac death were cold stored for 2 h after which they were perfused ex vivo in the absence and presence of mt-OGG1 or an inactive mt-OGG1 mutant. Lung endothelial barrier function and mtDNA integrity were determined during and at the end of perfusion, respectively. RESULTS AND CONCLUSIONS: Mitochondria-targeted OGG1 attenuated indices of lung endothelial dysfunction incurred after a 1h post-mortem period. Oxidative lung tissue mtDNA damage as well as accumulation of proinflammatory mtDNA fragments in lung perfusate, but not nuclear DNA fragments, also were reduced by mitochondria-targeted OGG1. A repair-deficient mt-OGG1 mutant failed to protect lungs from the adverse effects of DCD procurement. CONCLUSIONS: These findings suggest that endothelial barrier dysfunction in lungs procured after DCD is driven by mtDNA damage and point to strategies to enhance mtDNA repair in concert with EVLP as a means of alleviating DCD-related lung IR injury.


Assuntos
DNA Glicosilases/administração & dosagem , Endotélio Vascular/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Proteínas Recombinantes de Fusão/administração & dosagem , Traumatismo por Reperfusão/prevenção & controle , Aloenxertos/irrigação sanguínea , Aloenxertos/citologia , Aloenxertos/efeitos dos fármacos , Animais , DNA Glicosilases/genética , Reparo do DNA/efeitos dos fármacos , DNA Mitocondrial/efeitos dos fármacos , DNA Mitocondrial/genética , Modelos Animais de Doenças , Endotélio Vascular/citologia , Endotélio Vascular/patologia , Humanos , Pulmão/irrigação sanguínea , Pulmão/citologia , Pulmão/efeitos dos fármacos , Transplante de Pulmão , Masculino , Mitocôndrias/genética , Mitocôndrias/patologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Perfusão/métodos , Ratos , Proteínas Recombinantes de Fusão/genética , Traumatismo por Reperfusão/patologia , Coleta de Tecidos e Órgãos/métodos
4.
Medicine (Baltimore) ; 98(44): e17599, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689763

RESUMO

This study compares 2 methods of macular function evaluation: the microperimetric examination (mean central retinal sensitivity and fixation stability) and the distance best-corrected visual acuity (BCVA) examination, which is the most frequently used method of assessing macular function in patients with newly diagnosed wet age-related macular degeneration (AMD) who have been treated with anti-vascular endothelial growth factor (VEGF) drug (aflibercept).Prospective analysis was conducted on 44 eyes of 44 patients treated with intravitreal injection of anti-VEGF (aflibercept) because of newly diagnosed neovascular AMD. According to the research protocol, all patients had a 6-month follow-up. The response to treatment was monitored functionallybyMP-1 microperimetry, fixation, and distance BCVA assessment after injection. Improvement of retinal sensitivity and BCVA was found under aflibercept treatment. There was statistically significant improvement in retinal sensitivity in the MP-1 study 3 and 6 months from the beginning of anti-VEGF therapy. Moreover, a significant improvement in retinal sensitivity between 3 and 6 months of observation was demonstrated. At the same time, up to 3 months from the beginning of treatment, BCVA improved significantly compared to the baseline value. In the 6th month of the study BCVA remained stable without further significant improvement.Microperimetric examination with medium sensitivity and fixation stability assessment is a very valuable test determining the retinal function. It is clear that examining the macular morphology itself in modern diagnostics is not enough to assess retinal function. Microperimetry technique is a valuable tool for functional long-term evaluation of retinal function (also for a period of more than 3 months).


Assuntos
Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Retina/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/farmacologia , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/farmacologia , Acuidade Visual
5.
Medicine (Baltimore) ; 98(48): e17750, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770193

RESUMO

The aim of this study was to evaluate the cost-effectiveness of Anbainuo (ABN) plus methotrexate (MTX) (ABN + MTX) versus conventional disease-modifying anti-rheumatic drugs (cDMARDs) in rheumatoid arthritis (RA) patients.Forty-eight moderate to severe RA patients underwent ABN + MTX or cDMARDs treatment were consecutively enrolled and assigned to ABN + MTX group (n = 26) and control group (n = 22). Patients were followed up and their disease activity and quality of life (QoL) were evaluated at 3rd month, 6th month and 12th month after initiation of treatment. Treatment costs of 2 groups were calculated, then pharmacoeconomic analysis was performed.ABN + MTX increased drug cost and total cost while decreased indirect cost compared with cDMARDs after 12-month treatment. ABN + MTX group gained additional 0.22 quality-adjusted life years (QALY) and yielded an incremental cost-effectiveness ratio (ICER) of ¥104,293.6 per QALY after treatment. Sensitivity analysis reveals that rising ABN price by 20% produced an ICER of ¥130,403.6 per QALY, which was still lower than 3 times of the mean gross domestic product (GDP) per capita during the same period in China (¥165,960). Besides, ABN + MTX was more cost-effective in severe RA patients compared to moderate RA patients.ABN + MTX is cost-effective in treating moderate to severe RA patients compared with cDMARDs, although the total cost of ABN + MTX is relatively higher.


Assuntos
Antirreumáticos/economia , Artrite Reumatoide/tratamento farmacológico , Medicamentos Biossimilares/economia , Custos de Medicamentos/estatística & dados numéricos , Fragmentos Fc das Imunoglobulinas/economia , Metotrexato/economia , Receptores Tipo II do Fator de Necrose Tumoral/economia , Proteínas Recombinantes de Fusão/economia , Idoso , Antirreumáticos/administração & dosagem , Artrite Reumatoide/economia , Medicamentos Biossimilares/administração & dosagem , Análise Custo-Benefício , Quimioterapia Combinada/economia , Feminino , Humanos , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , Receptores Tipo II do Fator de Necrose Tumoral/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Índice de Gravidade de Doença , Resultado do Tratamento
6.
Ophthalmic Surg Lasers Imaging Retina ; 50(11): 684-690, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31755967

RESUMO

BACKGROUND AND OBJECTIVE: To report the correlation of central macular thickness (CMT) and best-corrected visual acuity (BCVA) after 1-year treatment by two doses (2.5 mg or 1.25 mg) of intravitreal ziv-aflibercept (IVZ) versus bevacizumab (IVB) in eyes with diabetic macular edema (DME). PATIENTS AND METHODS: In this study, the correlation of CMT and BCVA changes of the eyes enrolled in a previous clinical trial of 123 eyes were re-evaluated. The correlation of BCVA and CMT changes at each visit was evaluated in the three study arms individually. Then, the eyes in each of the arms were classified at each follow-up visit into three subgroups based on their CMT changes related to the baseline CMT: CMT decrease of 30% or more of baseline CMT, between 10% to 29% of baseline CMT, and less than 9% of baseline CMT or CMT increase. RESULTS: BCVA and CMT changes were correlated significantly (P < .05) in all and in half of the follow-up visits, respectively, in the eyes treated by IVZ 1.25 mg and IVB (r = 0.554 and r = 0.617 at 1 year, respectively). Nevertheless, such a significant correlation was not detected in the eyes treated by IVZ 2.5 mg in any of the follow-up visits (r = 0.202 at 1 year; P = .259). In the IVZ 2.5 mg group, BCVA improvement was observed in all subgroups with each level of CMT reductions. CONCLUSION: Ziv-aflibercept 2.5 mg might have a beneficial effect on DME beyond thickness reduction. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:684-690.].


Assuntos
Inibidores da Angiogênese/administração & dosagem , Bevacizumab/administração & dosagem , Retinopatia Diabética/complicações , Macula Lutea/patologia , Edema Macular/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Acuidade Visual/fisiologia , Adulto , Idoso , Retinopatia Diabética/tratamento farmacológico , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tomografia de Coerência Óptica
7.
Endocr Regul ; 53(3): 187-190, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31517629

RESUMO

OBJECTIVE: While dulaglutide has been approved inpatients with type 2 diabetes (T2DM) in combination with insulin, it has not been studied in insulin-deficient patients, not whether they have type 1 diabetes (T1DM) or T2DM. The aim of this study is to assess the efficacy and safety of dulaglutide 0.75 mg/once weekly (QW) in patients with absolute insulin deficiency (n=10). SUBJECTS AND RESULTS: Significant reductions of HbA1c (9.30±1.03% to 8.61±1.21%; p<0.02) and body mass index (BMI; 23.61±3.95 to 23.41±4.24; p<0.02) levels were observed at 3 months with the addition of dulaglutide to the existing pharmacotherapy. However, in all the patients, post-meal C-peptide levels remained undetectable. One patient had gastrointestinal adverse events and discontinue dulaglutide within the first month. One patient was a non-responder, who had little if any changes in HbA1c levels at 3 months. CONCLUSIONS: The results indicate that dulaglutide is effective in patients with T1DM or T2DM with absolute insulin deficiency, though gastrointestinal adverse events might be of concern. The improvements in glycemic control could not be due to enhanced insulin secretion, but may be as a result of a combination of the other effects of glucagon like peptide 1 (GLP-1), such as postprandial glucagon suppression, delayed gastric emptying, and weight loss.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Insulina/deficiência , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Idoso , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Esquema de Medicação , Quimioterapia Combinada , Feminino , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/efeitos dos fármacos , Hemoglobina A Glicada/metabolismo , Humanos , Insulina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
8.
BMJ Case Rep ; 12(9)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511273

RESUMO

Peripheral exudative haemorrhagic chorioretinopathy (PEHCR) is considered a variant of polypoidal choroidal vasculopathy. It may have varried presentations and systemic associations. We present a case of PEHCR which dramatically responded to intravitreal steroid and ziv-aflibercept injection. This case not only highlights the promising role of combination therapy with intravitreal steroids and ziv-aflibercept but also the need to look for any associated systemic comorbidity.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Degeneração Macular/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Hemorragia Retiniana/tratamento farmacológico , Triancinolona Acetonida/uso terapêutico , Idoso , Inibidores da Angiogênese/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Injeções Intravenosas , Injeções Intravítreas , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Triancinolona Acetonida/administração & dosagem
9.
Middle East Afr J Ophthalmol ; 26(2): 55-59, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31543660

RESUMO

PURPOSE: The aim of this study was to compare the pain scores of the patients during intravitreal injection of ranibizumab and aflibercept based on patient feedback. MATERIALS AND METHODS: Seventy-two eyes of 72 patients, who had not previously undergone any intravitreal injection procedures, were included in this study. Thirty-eight patients received ranibizumab, and 34 patients received aflibercept injections. The pain was measured by visual analog scale (VAS). Patients were asked to rate their pain experienced during the injection between 0 (no pain) and 10 (worst pain ever felt) on VAS just after the injection. RESULTS: VAS pain scores in ranibizumab and aflibercept groups were 3.28 ± 2.45 and 4.20 ± 2.30, respectively. There was a significant difference in average VAS pain scores between groups (P = 0.04). CONCLUSION: VAS pain scores in aflibercept group were found to be significantly higher than the scores in the ranibizumab group.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Dor Ocular/diagnóstico , Injeções Intravítreas/efeitos adversos , Ranibizumab/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Idoso , Dor Ocular/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Retrospectivos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular Exsudativa/tratamento farmacológico
10.
Graefes Arch Clin Exp Ophthalmol ; 257(11): 2559-2569, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31482277

RESUMO

PURPOSE: At present, the standard treatment of neovascular age-related macular degeneration (AMD) is the repeated administration of antivascular endothelial growth factor (VEGF) agents. However, we often encounter patients who develop tachyphylaxis for anti-VEGF agents. In this study, we investigated the characteristics of patients who developed tachyphylaxis on repeated intravitreal aflibercept (IVA) injections for neovascular AMD and the frequency of tachyphylaxis. METHODS: Three hundred thirteen eyes (313 patients) with treatment-naïve AMD who achieved resolution soon after starting IVA and were followed up for ≥ 12 months were enrolled in this retrospective, interventional, consecutive case series. The eyes were investigated for tachyphylaxis to aflibercept. Tachyphylaxis was defined as absence of any improvement (more than 100 µm) in or worsening of CRT within 1 month after more than two repeated monthly IVA injections when the exudative change remained. RESULTS: Twenty-eight (8.9%) of the 313 eyes developed tachyphylaxis (occult with no classic, n = 14; polypoidal choroidal vasculopathy, n = 14) at an annual rate of about 3%. The mean number of IVA injections was 10.5 ± 7.8, and the mean interval until tachyphylaxis was 20.9 ± 14.0 months. There was a significant difference in the AMD subtypes between the group with tachyphylaxis and the group without it (p = 0.0029). Occult with no classic type and polypoidal choroidal vasculopathy were the only AMD subtypes in the eyes with tachyphylaxis. In the analysis of the eyes that had occult with no classic or polypoidal choroidal vasculopathy, only intraretinal edema was significantly less common (p = 0.042). A combination of photodynamic therapy and aflibercept was effective in 13 (87%) of 15 eyes with tachyphylaxis, and switching to intravitreal ranibizumab was effective in 5 (56%) of 9 eyes. CONCLUSIONS: Tachyphylaxis occurs after repeated IVA injections in a minority of patients with AMD for a long term and is more likely to occur in eyes with lesions beneath the retinal pigment epithelium and no intraretinal edema. Treatment of AMD should be performed keeping this fact in mind, while considering the consecutive treatment.


Assuntos
Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Taquifilaxia , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Feminino , Angiofluoresceinografia/métodos , Seguimentos , Fundo de Olho , Humanos , Injeções Intravítreas , Masculino , Epitélio Pigmentado da Retina/patologia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular Exsudativa/diagnóstico
11.
Arch. Soc. Esp. Oftalmol ; 94(9): 460-464, sept. 2019. ilus
Artigo em Espanhol | IBECS | ID: ibc-186227

RESUMO

Varón de 61 años, con antecedentes personales de coroiditis serpiginosa (CS), que presentó metamorfopsia y disminución de agudeza visual (AV) en su ojo derecho (OD). En la exploración, mediante Swept-Source OCT-angiografía (SS OCT-A), se pudo observar una hemorragia peripapilar secundaria a una neovascularización coroidea (NVC). El paciente fue tratado mediante aflibercept intravítreo, presentando una evolución favorable en su sintomatología y en los hallazgos de la SS OCT-A. La NVC es una complicación que puede aparecer hasta en el 25% de los casos tras CS. Un diagnóstico preciso, mediante SS OCT-A, unido al tratamiento precoz con aflibercept, nos llevó a obtener unos óptimos resultados, tanto clínicos como anatómicos


A case is presented of a 61 year-old man with a personal history of serpiginous choroiditis (SC), who presented with metamorphopsia and decreased visual acuity (VA) in his right eye (RE). In the examination, using Swept Source OCT-angiography (SS OCT-A), peripapillary haemorrhage secondary to a choroidal neovascularisation (CNV) was observed. The patient was treated with intravitreal aflibercept, having a favourable outcome on his symptomatology and in the SS OCT-A findings. CNV is a complication that can appear in up to 25% of cases after SC. An accurate diagnosis using SS OCT-A, with early treatment with aflibercept, led us to obtain optimal clinical and anatomical results


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/etiologia , Angiofluoresceinografia , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Tomografia de Coerência Óptica , Inibidores da Angiogênese/administração & dosagem , Neovascularização de Coroide/diagnóstico por imagem , Neovascularização de Coroide/tratamento farmacológico , Injeções Intravítreas , Imagem Óptica , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem
12.
Jpn J Ophthalmol ; 63(5): 389-395, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31376050

RESUMO

PURPOSE: To determine the association of age-related maculopathy susceptibility 2 (ARMS2) gene polymorphisms with the 12-month outcomes of intravitreal aflibercept combined with photodynamic therapy (IVA+PDT) in polypoidal choroidal vasculopathy (PCV). STUDY DESIGN: Interventional cohort study. METHODS: This was a retrospective study of 48 consecutive treatment-naïve PCV patients. The patients underwent IVA+PDT as the initial therapy and were followed up for more than 12 months under a pro re nata regimen. The single nucleotide polymorphism (SNP) at rs10490924 in the ARMS2 gene was genotyped using the TaqMan assay. The clinical characteristics and outcomes of IVA+PDT were compared among the 3 genotypes at rs10490924. Multivariate regression analysis was performed to evaluate the influence of the clinical cofactors on the association of rs10490924 with the visual outcome at 12 months after the first IVA+PDT. RESULTS: No significant difference was found in the baseline characteristics among the 3 genotypes (n = 9, 23, and 16 for the GG, GT, and TT genotypes, respectively). All the patients, regardless of genotype, showed a significant improvement in vision, central retinal thickness, and subfoveal choroidal thickness at all time points measured after the initial IVA+PDT. The number of treatments was significantly smaller in the patients with the GG genotype than in those with the GT or the TT genotype. On multivariate logistic regression analysis, the number of the T allele at rs10490924 was significantly associated with the chance of retreatment after the initial IVA+PDT. CONCLUSION: The presence of the G allele at rs10490924 in the ARMS2 gene is likely associated with a lower chance of retreatment after IVA+PDT in patients with PCV.


Assuntos
Doenças da Coroide/tratamento farmacológico , Corioide/irrigação sanguínea , Predisposição Genética para Doença , Degeneração Macular/etiologia , Fotoquimioterapia/métodos , Pólipos/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Idoso , Alelos , Doenças da Coroide/complicações , Doenças da Coroide/diagnóstico , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Variação Genética , Humanos , Injeções Intravítreas , Degeneração Macular/diagnóstico , Degeneração Macular/genética , Masculino , Polimorfismo de Nucleotídeo Único , Pólipos/complicações , Pólipos/diagnóstico , Proteínas/genética , Proteínas/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Estudos Retrospectivos , Fatores de Tempo , Tomografia de Coerência Óptica , Acuidade Visual
13.
Int J Oncol ; 55(4): 823-832, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432158

RESUMO

The selective induction of tumor vascular thrombosis using truncated tissue factor (tTF) delivered via a target ligand is a promising novel antitumor strategy. In the present study, an anti­neuropilin­1 (NRP­1) monoclonal antibody (mAb)­streptavidin (SA):tTF­biotin (B) composite system was established. In this system, anti­NRP­1­mAb located tTF to the tumor vascular endothelial cell surface and induced vascular embolization. Due to their high binding affinity, SA and B were used to enhance thrombogenic activity. mAb was conjugated with SA using a coupling method with water­soluble 1­ethyl­3­(3­dimethylaminopropyl) carbodiimide and N­hydroxysulfosuccinimide. Biotinylated tTF (tTF­B) was prepared using a B­labeling kit subsequent to the generation and purification of fusion protein tTF. Confocal microscopy and flow cytometry indicated that the anti­NRP­1­mAb­SA conjugate retained mAb targeting activity. The preservation of B­conjugate binding capacity was confirmed using a competitive ELISA, and factor X­activation analysis revealed that tTF­B retained the procoagulant activity exhibited by tTF. Live imaging was performed to assess mAb­SA distribution and tumor­targeting capability, and this yielded promising results. The results of in vivo studies in mice with subcutaneous xenografts demonstrated that this composite system significantly induced tumor vascular thrombosis and inhibited tumor growth, whereas these histological changes were not observed in normal organs.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Neuropilina-1/imunologia , Tromboplastina/administração & dosagem , Trombose/induzido quimicamente , Animais , Antineoplásicos Imunológicos/química , Antineoplásicos Imunológicos/farmacologia , Fator X/metabolismo , Feminino , Células Hep G2 , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/metabolismo , Camundongos , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/farmacologia , Estreptavidina/química , Tromboplastina/química , Tromboplastina/farmacologia , Trombose/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Cutan Ocul Toxicol ; 38(4): 401-405, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31438736

RESUMO

Purpose: The aim of this study is to compare the efficacy of intravitreal injection of aflibercept and dexamethasone implant in the early treatment period of naive diabetic macular edema (DME) with serous retinal detachment (SRD). Materials and methods: In this retrospective comparative study, medical records of patients who received treatment for naive DME with SRD and underwent three monthly intravitreal aflibercept (IVA) injections (2 mg) or one intravitreal dexamethasone implant (IDI) injection (0.7 mg) were reviewed. The best corrected visual acuity (BCVA), central macular thickness (CMT), and presence and height of SRD were compared three months after IDI injection and one month after the third IVA injection. Results: A total of 57 eyes of 49 patients were included in the study. The IVA group consisted of 32 eyes of 27 patients, whereas the IDI group consisted of 25 eyes of 22 patients. Both groups were similar in terms of gender, baseline intraocular pressure, HbA1c levels, types of diabetes, BCVA, CMT, and height of SRD (p = 0.469, p = 0.089, p = 0.889, p = 0.461, p = 0.072, p = 0.073, and p = 0.064, respectively). The mean CMT changes were 228.6 ± 109.8 µm and 168.5 ± 106.4 µm in the IDI and IVA groups, respectively (p < 0.001 for both groups). The change in CMT was statistically significantly greater in IDI group than in IVA group (p = 0.041). The mean SRD changes were 162.7 ± 106.9 µm and 110.7 ± 51.9 µm in the IDI and IVA groups, respectively (p < 0.001 for both groups), and the change in SRD height was statistically significantly greater in IDI group than in IVA group (p = 0.019). SRD completely resolved in 92% and 91.2% of the patients in IDI and IVA groups, respectively (p = 0.856). Moreover, BCVA was significantly increased after the injections in both groups (p < 0.001 for both groups), and the change in BCVA was comparable between the groups (p = 0.245). Conclusions: Fewer injections of dexamethasone implant demonstrated better morphological results than aflibercept in the early treatment period of naive diabetic macular edema (DME) with serous retinal detachment (SRD).


Assuntos
Inibidores da Angiogênese/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Dexametasona/administração & dosagem , Complicações do Diabetes/tratamento farmacológico , Edema Macular/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Descolamento Retiniano/tratamento farmacológico , Adulto , Idoso , Implantes de Medicamento , Feminino , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade
15.
J Exp Clin Cancer Res ; 38(1): 332, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31362764

RESUMO

BACKGROUND: Immunotherapeutic approaches designed to augment T and B cell mediated killing of tumor cells has met with clinical success in recent years suggesting tremendous potential for treatment in a broad spectrum of tumor types. After complex recognition of target cells by T and B cells, delivery of the serine protease granzyme B (GrB) to tumor cells comprises the cytotoxic insult resulting in a well-characterized, multimodal apoptotic cascade. METHODS: We designed a recombinant fusion construct, GrB-Fc-4D5, composed of a humanized anti-HER2 scFv fused to active GrB for recognition of tumor cells and internal delivery of GrB, simulating T and B cell therapy. We assessed the construct's antigen-binding specificity and GrB enzymatic activity, as well as in vitro cytotoxicity and internalization into target and control cells. We also assessed pharmacokinetic and toxicology parameters in vivo. RESULTS: GrB-Fc-4D5 was highly cytotoxic to Her2 positive cells such as SKBR3, MCF7 and MDA-MB-231 with IC50 values of 56, 99 and 27 nM, respectively, and against a panel of HER2+ cell lines regardless of endogenous expression levels of the PI-9 inhibitor. Contemporaneous studies with Kadcyla demonstrated similar levels of in vitro activity against virtually all cells tested. GrB-Fc-4D5 internalized rapidly into target SKOV3 cells within 1 h of exposure rapidly delivering GrB to the cytoplasmic compartment. In keeping with its relatively high molecular weight (160 kDa), the construct demonstrated a terminal-phase serum half-life in mice of 39.2 h. Toxicity studies conducted on BALB/c mice demonstrated no statistically significant changes in SGPT, SGOT or serum LDH. Histopathologic analysis of tissues from treated mice demonstrated no drug-related changes in any tissues examined. CONCLUSION: GrB-Fc-4D5 shows excellent, specific cytotoxicity and demonstrates no significant toxicity in normal, antigen-negative murine models. This construct constitutes a novel approach against HER2-expressing tumors and is an excellent candidate for further development.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Desenvolvimento de Medicamentos , Terapia de Alvo Molecular , Receptor ErbB-2/antagonistas & inibidores , Proteínas Recombinantes de Fusão/farmacologia , Animais , Antígenos de Neoplasias/imunologia , Antineoplásicos Imunológicos/isolamento & purificação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Expressão Gênica , Vetores Genéticos/genética , Granzimas/administração & dosagem , Granzimas/genética , Humanos , Camundongos , Terapia de Alvo Molecular/métodos , Ligação Proteica/imunologia , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/isolamento & purificação , Anticorpos de Cadeia Única/genética , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Graefes Arch Clin Exp Ophthalmol ; 257(10): 2163-2172, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31367847

RESUMO

PURPOSE: To investigate the effects of anti-vascular endothelial growth factor (anti-VEGF) on the peripapillary choroid and choriocapillaris in eyes with neovascular age-related macular degeneration (nAMD). METHODS: We included consecutive patients who underwent three monthly intravitreal injections of aflibercept or ranibizumab for nAMD, followed by swept-source optical-coherence tomography angiography (SS-OCTA). Peripapillary choroidal thickness (CT) and vascular density (VD) of the peripapillary choriocapillaris were measured in SS-OCT and OCTA images at baseline and at 1 month after three monthly injections of anti-VEGF. RESULTS: In 68 eyes of 68 patients with nAMD, peripapillary CT decreased from 124.5 ± 69.9 µm to 116.5 ± 68.2 µm (P = 0.003) after three monthly intravitreal injections of anti-VEGF. The mean vascular density (VD) of the peripapillary choriocapillaris also decreased from 73.99 ± 6.33 to 71.82 ± 6.51 (P < 0.001). The change in the peripapillary choriocapillaris VD was significantly affected by baseline peripapillary choriocapillaris VD, baseline peripapillary CT, and type of nAMD (P = 0.004, P = 0.028, P = 0.015, respectively). The baseline VD of the choriocapillaris was lower in non-responders (median, 70.63; 25-75%, 68.12-71.27) than in responders (median, 75.32; 25-75%, 70.09-79.96) (P = 0.032). CONCLUSION: These results suggest that anti-VEGF injection influences the peripapillary choriocapillaris flow out of exudative lesions, and that its effects depend on the baseline status of the choroid and choriocapillaris.


Assuntos
Capilares/patologia , Corioide/irrigação sanguínea , Angiofluoresceinografia/métodos , Ranibizumab/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Tomografia de Coerência Óptica/métodos , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Inibidores da Angiogênese/administração & dosagem , Feminino , Seguimentos , Fundo de Olho , Humanos , Masculino , Disco Óptico/irrigação sanguínea , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual , Degeneração Macular Exsudativa/diagnóstico
17.
Expert Rev Clin Pharmacol ; 12(10): 941-946, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31465247

RESUMO

Introduction: CD123 or interleukin 3 receptor alpha is overexpressed in multiple hematologic malignancies. Tagraxofusp is an intravenously administered CD123-directed cytotoxin consisting of the fusion of interleukin-3 with a truncated diphtheria toxin payload and was recently approved by the Food and Drug Administration for the treatment of adults and children aged 2 and older with blastic plasmacytoid dendritic cell neoplasm (BPDCN). Areas Covered: In this review, we discuss the use of tagraxofusp in BPDCN, and active clinical trials involving this agent in several hematologic malignancies are also presented. Tagraxofusp has significant efficacy in patients with BPDCN and manageable safety profile, with the most commonly reported adverse events being asymptomatic elevation of alanine and aspartate aminotransferase levels, hypoalbuminemia, peripheral edema, and thrombocytopenia. The most serious side effect is capillary leak syndrome that can be lethal in some cases but the risk may be mitigated by early recognition and intervention. Expert Opinion: Tagraxofusp has been introduced as a novel treatment of BPDCN, a rare hematologic malignancy, for which no standard therapy previously existed. Many patients treated with this agent were able to be bridged to stem cell transplantation, including older patients. In the future, combinations of tagraxofusp with other targeted agents will be explored.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Hematológicas/tratamento farmacológico , Proteínas Recombinantes de Fusão/administração & dosagem , Adulto , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Criança , Pré-Escolar , Células Dendríticas/patologia , Neoplasias Hematológicas/patologia , Humanos , Subunidade alfa de Receptor de Interleucina-3/imunologia , Terapia de Alvo Molecular , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/farmacologia , Transplante de Células-Tronco/métodos
18.
Mar Biotechnol (NY) ; 21(5): 697-706, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31372794

RESUMO

The availability of sexually mature fish often dictates the success of its captive breeding. In this study, we induced reproductive development in juvenile protogynous tiger grouper through oral administration of a plasmid (p) containing an engineered follicle-stimulating hormone (FSH). An expression construct (pcDNA3.1) was designed to express a single-chain FSH consisting of giant grouper FSH ß-subunit and glycoprotein subunit-α (CGα), linked by the carboxy-terminal peptide (CTP) sequence from the human chorionic gonadotropin (hCG). Single oral delivery of pFSH encapsulated in liposome and chitosan to tiger grouper yielded a significant increase in plasma FSH protein level after 4 days. Weekly pFSH feeding of juvenile tiger groupers for 8 weeks stimulated ovarian development as indicated by a significant increase in oocyte diameter and progression of oocytes to cortical alveolar stage. As the pFSH treatment progressed from 20 to 38 weeks, female to male sex change was initiated, characterized by oocyte regression, proliferation of spermatogonial cells, and occurrence of spermatogenic cysts. It was also associated with significantly lower mRNA expression of steroidogenic genes (cyp11b, cyp19a1a, and foxl2) and basal plasma levels of sex steroid hormones 17ß-estradiol (E2), testosterone (T), and 11-ketotestosterone (11KT). Results suggest that pFSH stimulates ovarian development up to cortical alveolar stage and then initiates sex change in tiger grouper. These findings significantly contribute to our knowledge on the role of FSH in the development of protogynous hermaphroditic fish. This study is the first to demonstrate induction of reproductive development in fish through oral delivery of plasmid gonadotropin.


Assuntos
Gonadotropina Coriônica/genética , Hormônio Foliculoestimulante/genética , Gônadas/efeitos dos fármacos , Organismos Hermafroditas/efeitos dos fármacos , Perciformes/genética , Processos de Determinação Sexual/efeitos dos fármacos , Diferenciação Sexual/efeitos dos fármacos , Administração Oral , Animais , Quitosana/química , Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/biossíntese , Composição de Medicamentos , Feminino , Proteínas de Peixes/biossíntese , Proteínas de Peixes/genética , Hormônio Foliculoestimulante/administração & dosagem , Hormônio Foliculoestimulante/biossíntese , Hormônios Esteroides Gonadais/biossíntese , Hormônios Esteroides Gonadais/genética , Gônadas/crescimento & desenvolvimento , Gônadas/metabolismo , Organismos Hermafroditas/genética , Humanos , Lipossomos/administração & dosagem , Lipossomos/química , Masculino , Oogênese/efeitos dos fármacos , Oogênese/genética , Perciformes/crescimento & desenvolvimento , Perciformes/metabolismo , Plasmídeos/química , Plasmídeos/metabolismo , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Pré-Seleção do Sexo/métodos , Espermatogênese/efeitos dos fármacos , Espermatogênese/genética
19.
Graefes Arch Clin Exp Ophthalmol ; 257(9): 1889-1895, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31256237

RESUMO

PURPOSE: To compare treatment efficacy of anti-VEGF medications following pro re nata (PRN, "as needed", monthly injections only in case of active disease) or treat and extend (T&E, progressive extension of treatment intervals up to 12 weeks depending on the clinical findings) treatment protocols in real-world conditions. METHODS: Retrospective, observational study. Patients diagnosed with age-related macular degeneration and without pre-treatment undergoing routine anti-VEGF treatment in one eye clinic in Switzerland were included. Treatment was performed according to local practices, using ranibizumab or aflibercept, and following T&E or PRN regimens. Changes in logMAR and injection intervals (time between two injections) for specific treatment periods were evaluated descriptively and using mixed models. RESULTS: In total, 1071 patients with 1332 treated eyes (ranibizumab/PRN 722, ranibizumab/T&E 191, aflibercept/T&E 419) were included in the analyses. At baseline, logMAR (mean ± SD) was similar in both ranibizumab treatment groups (PRN 0.63 ± 0.43, T&E 0.57 ± 0.42). In the ranibizumab/PRN group, logMAR was about 0.1 lower for all time intervals in the initial and maintenance phases in comparison with baseline, indicating an improvement in VA. By comparison, logMAR improved more strongly in the ranibizumab/T&E group (16 to < 22 months, - 0.19 [- 0.23-0.15]) in comparison with baseline. Comparing ranibizumab/T&E vs. aflibercept/T&E groups, improvements in logMAR were similar over time. In the maintenance phase, the rate of patients with a clinically relevant improvement in visual acuity (> 0.2 logMAR) was higher in both T&E groups compared with the ranibizumab/PRN group. Injection intervals in the maintenance phase in ranibizumab/T&E group gradually expanded over time; whereas in the aflibercept/T&E group, injection intervals remained relatively stable. CONCLUSIONS: Ranibizumab used according to T&E protocol yielded a stronger improvement in logMAR, compared with PRN protocol with longer injection intervals than aflibercept/T&E. This large real-world data assessment supports previous data on the superiority of T&E treatment.


Assuntos
Macula Lutea/patologia , Ranibizumab/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Acuidade Visual , Degeneração Macular Exsudativa/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Degeneração Macular Exsudativa/diagnóstico
20.
Graefes Arch Clin Exp Ophthalmol ; 257(10): 2119-2125, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31286206

RESUMO

PURPOSE: To analyze and compare loss to follow-up (LTFU) rates between patients with diabetic retinopathy (DR) and those with neovascular age-related macular degeneration (nAMD) in patients, receiving treatment with anti-vascular endothelial growth factor (VEGF), under universal health coverage. METHODS: We retrospectively analyzed the relevant data of 1264 patients receiving anti-VEGF therapy, in this cohort study. The observation period ranged from September 01, 2015 to December 31, 2018. Intervals between each procedure and the subsequent follow-up examination were measured. Demographic data, visual acuity (VA), the type of transport for treatment access, and distance between the residence and clinic were evaluated as risk factors for LTFU. RESULTS: We collected data for 841 patients with nAMD (age, 81.0 (± 8.1 years)) and 423 patients with DR (age, 67.7 (± 12.1 years)). The rate of LTFU, for at least 6 months, was 28.8% and 2.9% for patients with DR and nAMD, respectively (p < 0.001). In the DR group, 18.9% patients were lost to follow-up exceeding > 12 months. Multivariate regression analysis showed that advanced age, lack of mobility, and need for assisted transport, poor final VA despite treatment, and decrease in vision during the observational period were independent risk factors for LTFU exceeding 12 months (p < 0.05). CONCLUSIONS: We found a high long-term LTFU rate for patients with DR, despite treatment under universal health coverage. Considering the risk of disease progression, particularly in patients with chronic DR, strategies for better compliance and adherence to therapy should be considered for optimized patient care.


Assuntos
Retinopatia Diabética/tratamento farmacológico , Cobertura do Seguro , Degeneração Macular/tratamento farmacológico , Cooperação do Paciente , Ranibizumab/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Acuidade Visual , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/economia , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Macula Lutea/patologia , Degeneração Macular/diagnóstico , Degeneração Macular/economia , Masculino , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento
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