RESUMO
Currently, biological drug therapy for ocular angiogenesis treatment is based on the administration of anti-VEGF agents via intravitreal route. The molecules approved with this purpose for ocular use include pegaptanib, ranibizumab, and aflibercept, whereas bevacizumab is commonly off-label used in the clinical practice. The schedule dosage involves repeated intravitreal injections of anti-VEGF agents to achieve and maintain effective concentrations in retina and choroids, which are administrated as solutions form. In this review article, we describe the features of different anti-VEGF agents, major challenges for their ocular delivery and the nanoparticles in development as delivery system of them. In this way, several polymeric and lipid nanoparticles are explored to load anti-VEGF agents with the aim of achieving sustained drug release and thus, minimize the number of intravitreal injections required. The main challenges were focused in the loading the molecules that maintain their bioactivity after their release from nanoparticulate system, followed the evaluation of them through studies of formulation stability, pharmacokinetic, and efficacy in in vitro and in vivo models. The analysis was based on the information published in peer-reviewed published papers relevant to anti-VEGF treatments and nanoparticles developed as ocular anti-VEGF delivery system.
Assuntos
Inibidores da Angiogênese/administração & dosagem , Produtos Biológicos/administração & dosagem , Sistemas de Liberação de Fármacos por Nanopartículas/química , Neovascularização Patológica/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacocinética , Produtos Biológicos/química , Produtos Biológicos/farmacocinética , Retinopatia Diabética/tratamento farmacológico , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Olho/irrigação sanguínea , Olho/efeitos dos fármacos , Olho/patologia , Humanos , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Nanopartículas/química , Neovascularização Patológica/patologia , Oclusão da Veia Retiniana/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Ocular ischemia syndrome is caused by ocular chronic hypoperfusion due to stenosis or occlusion of the ipsilateral common or internal carotid artery. We present the case of a 58-year-old male with recurrent unilateral amaurosis fugax, ophthalmological examination compatible with chronic ocular ischemia, and severe stenosis of ipsilateral internal carotid artery. After angioplasty and stenting of the carotid stenosis, the findings resolved.
El síndrome de isquemia ocular es causado por la hipoperfusión ocular crónica debido a estenosis u oclusión de arteria carótida común o interna ipsilateral. Presentamos el caso de un varón de 58 años con episodios de amaurosis fugax unilateral, exploración oftalmológica compatible con isquemia ocular crónica y estenosis severa de arteria carótida interna ipsilateral. Tras la angioplastia y stent de la zona de estenosis carotídea, los hallazgos resolvieron.
Assuntos
Estenose das Carótidas/complicações , Olho/irrigação sanguínea , Isquemia/etiologia , Olho/diagnóstico por imagem , Humanos , Isquemia/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , SíndromeRESUMO
Resumo Objetivo: Avaliar a variação da pressão intraocular e da pressão de perfusão ocular durante sessão de hemodiálise, nos períodos pré, intra (a cada hora) e pós dialítico, em pacientes tratados em Serviços de Referência em hemodiálise da cidade de Fortaleza - CE. Métodos: O estudo foi longitudinal e prospectivo. 45 pacientes foram submetidos à hemodiálise. Todos os pacientes foram recrutados a fazer um exame oftalmológico, além da aferição da pressão intraocular com o Tonopen. Resultados: A amostra foi composta por 26 homens e 19 mulheres com idade média de 51,8 anos. O estudo revelou que há uma diferença importante entre a pressão intraocular pré e pós hemodiálise, diminuindo em média 2,59 mmHg. Ao analisar a pressão de perfusão ocular, foi encontrado um aumento médio de 1,85 mmHg entre o início e o término da hemodiálise. Conclusão: De acordo com o presente estudo, o processo de hemodiálise é um procedimento aparentemente seguro em relação à alteração da pressão intraocular e da pressão de perfusão ocular, como causadores de patologias oculares, principalmente o glaucoma.
Abstract Objective: To evaluate the variation of intraocular pressure and ocular perfusion pressure during hemodialysis sessions, in the pre, intra (hourly) and post dialytic periods, in patients treated at Hemodialysis Reference Services in Fortaleza - CE. Methods: The study was longitudinal and prospective. 45 patients underwent hemodialysis. All patients were recruited to undergo an ophthalmologic examination, in addition to the intraocular pressure measurement with Tonopen. Results: The sample consisted of 26 men and 19 women with a mean age of 51.8 years. The study revealed that there is an important difference between pre and post hemodialysis intraocular pressure, decreasing by an average of 2.59 mmHg. When analyzing ocular perfusion pressure, an average increase of 1.85 mmHg was found between the onset and end of hemodialysis. Conclusion: According to the present study, the hemodialysis process is an apparently safe procedure in relation to altered intraocular pressure and ocular perfusion pressure, as causes of ocular pathologies, mainly glaucoma.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Pressão Sanguínea/fisiologia , Diálise Renal , Olho/irrigação sanguínea , Pressão Intraocular/fisiologia , Oftalmoscopia , Fluxo Sanguíneo Regional , Fatores de Tempo , Tonometria Ocular , Acuidade Visual , Estudos Prospectivos , Estudos Longitudinais , Microscopia com Lâmpada de FendaRESUMO
Variable new antigen receptor domain (vNAR) antibodies are novel, naturally occurring antibodies that can be isolated from naïve, immune or synthetic shark libraries. These molecules are very interesting to the biotechnology and pharmaceutical industries because of their unique characteristics related to size and tissue penetrability. There have been some approved anti-angiogenic therapies for ophthalmic conditions, not related to vNAR. This includes biologics and chimeric proteins that neutralize vascular endothelial growth factor (VEGF)165, which are injected intravitreal, causing discomfort and increasing the possibility of infection. In this paper, we present a vNAR antibody against human recombinant VEGF165 (rhVEGF165) that was isolated from an immunized Heterodontus francisci shark. A vNAR called V13, neutralizes VEGF165 cytokine starting at 75 µg/mL in an in vitro assay based on co-culture of normal human dermal fibroblasts (NHDFs) and green fluorescence protein (GFP)-labeled human umbilical vein endothelial cells (HUVECs) cells. In the oxygen-induced retinopathy model in C57BL/6:Hsd mice, we demonstrate an endothelial cell count decrease. Further, we demonstrate the intraocular penetration after topical administration of 0.1 µg/mL of vNAR V13 by its detection in aqueous humor in New Zealand rabbits with healthy eyes after 3 h of application. These findings demonstrate the potential of topical application of vNAR V13 as a possible new drug candidate for vascular eye diseases.
Assuntos
Produtos Biológicos/farmacocinética , Doenças Retinianas/tratamento farmacológico , Tubarões , Anticorpos de Domínio Único/farmacologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Administração Tópica , Animais , Produtos Biológicos/imunologia , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/uso terapêutico , Células Cultivadas , Técnicas de Cocultura , Modelos Animais de Doenças , Olho/irrigação sanguínea , Olho/metabolismo , Fibroblastos , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Soluções Oftálmicas/farmacocinética , Soluções Oftálmicas/uso terapêutico , Oxigênio/toxicidade , Coelhos , Proteínas Recombinantes/metabolismo , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/patologia , Anticorpos de Domínio Único/imunologia , Anticorpos de Domínio Único/isolamento & purificação , Anticorpos de Domínio Único/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/imunologia , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Background: Contrast Enchantment Ultrasonography (CEUS) allows for detection of vascular flows that are difficult to detect with traditional methods. There were no reports found in the literature of the use of CEUS to evaluate the vascular pattern of the eye of brachycephalic dogs. The objective of this paper is to describe ultrasound findings observed in the eyes of healthy brachycephalic dogs subjected to CEUS.Materials, Methods & Results: Thirty adult brachycephalic dogs were subjected to physical, laboratorial, and ophthalmic examination. The eye structures were evaluated using CEUS after intravenous administration of Sonovue®. Contrast enhancement was seen in 52 eyes with a homogeneous and centrifugal filling pattern. Structures adequately enhanced consisted of the optic nerve, the retina-choroid-sclera complex (RCSC), and the ciliary body. The optic nerve was hyperenhanced and the other structures were isoenhanced. The wash-in time, peak enhancement time, and wash-out time were similar for both right and left eyes. Mean values and standard deviation were calculated for contrast wash-in time, peak enhancement time, and wash-out time in the optic nerve, RCSC, and ciliary body.Discussion: Ultrasound is an important diagnostic resource for veterinary ophthalmology and provides relevant information for the detection of pathological conditions of the eyes of animals. The contrast-enhanced ultrasound allows evaluation of tissues at the capillary level (macro and microcirculation), complementing the vascular ultrasound scan. This study brings original information on contrast-enhanced ultrasound findings for evaluation of eyes in dogs, creating novel diagnostic possibilities for the use of this imaging technique in veterinary ophthalmology.[...](AU)
Assuntos
Animais , Cães , Ultrassonografia/métodos , Ultrassonografia/veterinária , Olho/diagnóstico por imagem , Corpo Ciliar , Olho/irrigação sanguínea , Meios de Contraste , Retina , Nervo ÓpticoRESUMO
Background: Contrast Enchantment Ultrasonography (CEUS) allows for detection of vascular flows that are difficult to detect with traditional methods. There were no reports found in the literature of the use of CEUS to evaluate the vascular pattern of the eye of brachycephalic dogs. The objective of this paper is to describe ultrasound findings observed in the eyes of healthy brachycephalic dogs subjected to CEUS.Materials, Methods & Results: Thirty adult brachycephalic dogs were subjected to physical, laboratorial, and ophthalmic examination. The eye structures were evaluated using CEUS after intravenous administration of Sonovue®. Contrast enhancement was seen in 52 eyes with a homogeneous and centrifugal filling pattern. Structures adequately enhanced consisted of the optic nerve, the retina-choroid-sclera complex (RCSC), and the ciliary body. The optic nerve was hyperenhanced and the other structures were isoenhanced. The wash-in time, peak enhancement time, and wash-out time were similar for both right and left eyes. Mean values and standard deviation were calculated for contrast wash-in time, peak enhancement time, and wash-out time in the optic nerve, RCSC, and ciliary body.Discussion: Ultrasound is an important diagnostic resource for veterinary ophthalmology and provides relevant information for the detection of pathological conditions of the eyes of animals. The contrast-enhanced ultrasound allows evaluation of tissues at the capillary level (macro and microcirculation), complementing the vascular ultrasound scan. This study brings original information on contrast-enhanced ultrasound findings for evaluation of eyes in dogs, creating novel diagnostic possibilities for the use of this imaging technique in veterinary ophthalmology.[...]
Assuntos
Animais , Cães , Corpo Ciliar , Olho/diagnóstico por imagem , Olho/irrigação sanguínea , Ultrassonografia/métodos , Ultrassonografia/veterinária , Meios de Contraste , Nervo Óptico , RetinaRESUMO
OBJECTIVE: To examine the association of ophthalmic artery (OA) Doppler measure - the ratio of velocity peaks (PR) - to adverse pregnancy outcomes in preeclampsia. STUDY DESIGN AND MAIN OUTCOMES: Prospective cohort study of 56 women with preeclampsia that underwent Doppler measurements of OA flow, medial to optic nerve. PR results were classified as normal (PR < 0.78), abnormal (PR 0.78-0.98), or highly abnormal (PR ≥ 0.99). Attending clinicians were blinded to OA Doppler results. The primary endpoints were (1) a composite of adverse maternal outcomes-central nervous system injury (eclampsia or posterior reversible encephalopathy syndrome), HELLP syndrome, hypertensive crisis, maternal admission to the intensive care unit, and maternal death-and (2) a composite of adverse perinatal outcomes-birth weight <10th percentile for gestational age, neonatal acidemia, 5-min Apgar score <7, admission of infants weighing >2500 g to the neonatal intensive care, preterm birth <32 weeks, fetal or neonatal death. RESULTS: Adverse maternal outcomes became more frequent as the PR values increased (p=.005). The occurrence of hypertensive crisis after hospital admission (secondary endpoint) was also positively associated with PR values (p=.001). Adverse perinatal outcomes were not associated with PR values (p=.551), but women in the highly abnormal PR group (PR ≥ 0.99) had the earliest deliveries (p=.001) and the smallest newborns (p=.004). All women in the highly abnormal PR group (n=16) had an adverse outcome. CONCLUSIONS: Maternal OA Doppler PR ≥ 0.99 in preeclampsia may identify women at increased risk of adverse maternal outcomes and pregnancies at the greatest risk of preterm birth.
Assuntos
Olho/irrigação sanguínea , Artéria Oftálmica/fisiologia , Pré-Eclâmpsia/epidemiologia , Ultrassonografia Pré-Natal , Adulto , Velocidade do Fluxo Sanguíneo , Brasil/epidemiologia , Estudos de Coortes , Feminino , Humanos , Pré-Eclâmpsia/fisiopatologia , Gravidez , Resultado da Gravidez , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
PURPOSE: To evaluate intraocular pressure (IOP) and extraocular orbital vessels with color Doppler ultrasound (CDU) and investigate the effects of obesity on retrobulbar blood flow. METHODS: Fifty-nine patients were included in this prospective study. Patients were divided into two groups according to body mass index: Group 1 (31 obese patients) and Group 2 (28 non-obese patients). IOP was measured with a Goldmann applanation tonometer, and CDU was used to evaluate the retrobulbar vessels. RESULTS: The mean IOP was 18 ± 6.68 mmHg in the obese group and 13.71 ± 1.60 mmHg in the control group (p<0.001). When the CDU values for the central retinal artery were compared between the groups, the pulsatility index was found to be significantly lower in the obese group than in the control group (p<0.001). When the CDU values for the ophthalmic artery (OA) were compared between the groups, the peak systolic velocity (p<0.001) and end-diastolic velocity (p=0.002) values were found to be significantly lower in the obese group than in the control group. CONCLUSIONS: Obese patients have a higher mean IOP and lower flow velocity than non-obese patients. Increased IOP together with decreased retrobulbar blood flow, particularly in obese individuals, may increase the risk of glaucoma development.
Assuntos
Pressão Intraocular/fisiologia , Obesidade/fisiopatologia , Artéria Oftálmica/fisiopatologia , Fluxo Sanguíneo Regional/fisiologia , Artéria Retiniana/fisiopatologia , Adulto , Fatores Etários , Índice de Massa Corporal , Estudos de Casos e Controles , Olho/irrigação sanguínea , Feminino , Glaucoma/etiologia , Hemodinâmica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Oftálmica/diagnóstico por imagem , Estudos Prospectivos , Valores de Referência , Artéria Retiniana/diagnóstico por imagem , Fatores de Risco , Fatores Sexuais , Estatísticas não Paramétricas , Tonometria Ocular , Ultrassonografia Doppler em CoresRESUMO
ABSTRACT Purpose: To evaluate intraocular pressure (IOP) and extraocular orbital vessels with color Doppler ultrasound (CDU) and investigate the effects of obesity on retrobulbar blood flow. Methods: Fifty-nine patients were included in this prospective study. Patients were divided into two groups according to body mass index: Group 1 (31 obese patients) and Group 2 (28 non-obese patients). IOP was measured with a Goldmann applanation tonometer, and CDU was used to evaluate the retrobulbar vessels. Results: The mean IOP was 18 ± 6.68 mmHg in the obese group and 13.71 ± 1.60 mmHg in the control group (p<0.001). When the CDU values for the central retinal artery were compared between the groups, the pulsatility index was found to be significantly lower in the obese group than in the control group (p<0.001). When the CDU values for the ophthalmic artery (OA) were compared between the groups, the peak systolic velocity (p<0.001) and end-diastolic velocity (p=0.002) values were found to be significantly lower in the obese group than in the control group. Conclusions: Obese patients have a higher mean IOP and lower flow velocity than non-obese patients. Increased IOP together with decreased retrobulbar blood flow, particularly in obese individuals, may increase the risk of glaucoma development.
RESUMO Objetivo: Avaliar a pressão intraocular (PIO) e vasos orbitários extraoculares com ultrassom Doppler colorido (UDC) e investigar os efeitos da obesidade sobre o fluxo sanguíneo retrobulbar. Métodos: Cinquenta e nove pacientes foram incluídos neste estudo prospectivo. Os pacientes foram divididos em dois grupos de acordo com o índice de massa corpo ral (IMC): Grupo 1 (31 pacientes obesos) e Grupo 2 (28 não obesos). As pressões intraoculares (PIOs) foram medidas com tonômetro de aplanação de Goldmann e o UDC foi utilizada para a avaliação de vasos retrobulbar. Resultados: As PIOs foram 18 ± 6,68 mmHg nos pacientes obesos e 13,71 ± 1,60 mmHg nos grupos controle (p<00,001). Quando os valores da artéria central da retina (ACR) foram comparados entre os grupos controle e obeso. O índice pulsátil (PI) foi marcadamente menor no grupo obeso (p<00,001). Quando os valores da artéria oftálmica (AO) dos grupos obesos e de controle foram comparados. Os valores de Velocidade do pico sistólico (PSV) (p<00,001) e velocidade diastólica final (EDV) (p=00,002) foram significativamente mais baixos no grupo obeso. Conclusão: Pacientes obesos têm maior PIO do que os pacientes não obesos. Os pacientes obesos têm diminuição nas velocidades de fluxo da AO. O aumento da PIO. Juntamente com a diminuição do fluxo sanguíneo retrobulbar, especialmente em indivíduos obesos, pode aumentar o risco de desenvolvimento de glaucoma.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Artéria Oftálmica/fisiopatologia , Fluxo Sanguíneo Regional/fisiologia , Artéria Retiniana/fisiopatologia , Pressão Intraocular/fisiologia , Obesidade/fisiopatologia , Artéria Oftálmica/diagnóstico por imagem , Valores de Referência , Artéria Retiniana/diagnóstico por imagem , Tonometria Ocular , Índice de Massa Corporal , Estudos de Casos e Controles , Fatores Sexuais , Glaucoma/etiologia , Estudos Prospectivos , Fatores de Risco , Fatores Etários , Ultrassonografia Doppler em Cores , Estatísticas não Paramétricas , Olho/irrigação sanguínea , Hemodinâmica/fisiologiaRESUMO
PURPOSE: To assess the effect of hemodialysis on retinal and choroidal thicknesses using spectral-domain optical coherence tomography (SD-OCT). METHODS: In this prospective interventional study, 25 hemodialysis patients (17 male, 8 female) were enrolled. All participants underwent high-speed, high-resolution SD-OCT (λ=840 mm; 26.000 A-scans/s; 5 µm resolution) before and after hemodialysis. Choroidal thickness was measured perpendicularly from the outer edge of the retinal pigment epithelium to the choroid-sclera boundary at the fovea and at five additional points: 500 µm and 1000 µm nasal to the fovea and 500 µm, 1000 µm, and 1500 µm temporal to the fovea. Two masked physicians performed the measurements. Choroidal and retinal thicknesses before and after hemodialysis were compared. RESULTS: The median choroidal thicknesses before and after hemodialysis were 182 µm (range, 103-374 µm) and 161 µm (range, 90-353 µm), respectively (P<0.001). The median retinal thicknesses were 246 µm (range, 179-296 µm) before and 248 µm (range, 141-299 µm) after hemodialysis (P>0.05). Systolic arterial pressure, diastolic arterial pressure, mean arterial pressure, heart rate, and ocular perfusion pressure significantly decreased after hemodialysis (P<0.001). Intraocular pressure did not vary significantly (P=0.540). CONCLUSION: Hemodialysis seems to cause a significant decrease in choroidal thickness, whereas it has no effect on retinal thickness. This significant decrease in choroidal thickness might be due to the extensive fluid absorption in hemodialysis, which could result in decreased ocular blood flow.