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Complications from diabetic retinopathy such as diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) constitute leading causes of preventable vision loss in working-age patients. Since vascular endothelial growth factor (VEGF) plays a major role in the pathogenesis of these complications, VEGF inhibitors have been the cornerstone of their treatment. Anti-VEGF monotherapy is an effective but burdensome treatment for DME. However, due to the intensive and burdensome treatment, most patients in routine clinical practice are undertreated, and therefore, their outcomes are compromised. Even in adequately treated patients, persistent DME is reported anywhere from 30% to 60% depending on the drug used. PDR is currently treated by anti-VEGF, panretinal photocoagulation (PRP) or a combination of both. Similarly, a number of eyes, despite these treatments, continue to progress to tractional retinal detachment and vitreous hemorrhage. Clearly there are other molecular pathways other than VEGF involved in the pathogenesis of DME and PDR. One of these pathways is the angiopoietin-Tie signaling pathway. Angiopoietin 1 (Ang1) plays a major role in maintaining vascular quiescence and stability. It acts as a molecular brake against vascular destabilization and inflammation that is usually promoted by angiopoietin 2 (Ang2). Several pathological conditions including chronic hyperglycemia lead to Ang2 upregulation. Recent regulatory approval of the bi-specific antibody, faricimab, may improve long term outcomes in DME. It targets both the Ang/Tie and VEGF pathways. The YOSEMITE and RHINE were multicenter, double-masked, randomized non-inferiority phase 3 clinical trials that compared faricimab to aflibercept in eyes with center-involved DME. At 12 months of follow-up, faricimab demonstrated non-inferior vision gains, improved anatomic outcomes and a potential for extended dosing when compared to aflibercept. The 2-year results of the YOSEMITE and RHINE trials demonstrated that the anatomic and functional results obtained at the 1 year follow-up were maintained. Short term outcomes of previously treated and treatment-naive eyes with DME that were treated with faricimab during routine clinical practice suggest a beneficial effect of faricimab over other agents. Targeting of Ang2 has been reported by several other means including VE-PTP inhibitors, integrin binding peptide and surrobodies.
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ABSTRACT Purpose: Intravitreal antiangiogenic therapy is currently the most invasive ophthalmic procedure performed worldwide. This study aimed to describe the clinical and epidemiological profile of patients undergoing intravitreal antiangiogenic therapy in a tertiary referral hospital in Brazil. Methods: This cross-sectional, retrospective, and observational study analyzed medical records of patients who received intravitreal injections of antiangiogenic agents for the treatment of retinal diseases at the ophthalmology outpatient clinic in the Hospital das Clínicas at Unicamp between January and December 2020. Results: The study included 429 patients and 514 eyes. The study population was predominantly male (51.28%), white (80.89%), between 50 and 80 years old (mean age, 60.92 years), had complete or incomplete first-grade education (56.88%), and did not belong to the Regional Health Department of which Campinas is a part (78.55%). Bevacizumab was the most commonly used intravitreal injectable medicine (79.38%), pro re nata was the most commonly used treatment regimen (90.27%), and macular edema was the most prevalent pathology indicative of treatment (60.12%), with diabetes etiology accounting for 48.25%. The average number of injections per patient was 3.83, with the macular neovascularization group and the pro re nata group having the highest and lowest with five and three injections, respectively. Treatment adherence was associated with the patient's pathology, and the macular edema (52.24%) and macular neovascularization (49.48%) groups had the lowest adherence rates. Conclusions: This study evaluated the epidemiological and clinical profile of patients undergoing antiangiogenic therapy in a high-complexity public hospital, which is fundamental for a better understanding of the demand for ophthalmic reference service in Brazil, and the analysis of functional results and user adherence profile promotes optimization of indications and leverages the benefits of intravitreal therapy.
RESUMO Objetivo: A terapia antiangiogênica intravítrea revolucionou o tratamento de inúmeras patologias de relevância global, sendo atualmente o procedimento oftalmológico invasivo mais realizado no mundo. Objetiva-se no presente estudo descrever o perfil clínico e epidemiológico dos pacientes submetidos a terapia intravítrea com antiangiogênicos em hospital terciário de referência no Brasil. Métodos: Trata-se de um estudo transversal, retrospectivo e observacional que foi realizado através da análise de prontuários de pacientes submetidos a injeção intravítrea de antiangiogênicos para tratamento de doenças retinianas no ambulatório de oftalmologia do Hospital das Clínicas da Unicamp no período de janeiro a dezembro de 2020. Resultados: O estudo analisou 429 pacientes e 514 olhos. A maioria pertencia ao sexo masculino (51,28%), raça branca (80,89%), possuía entre 50-80 anos com idade média de 60,92 anos e escolaridade de 1º grau completo ou incompleto (56,88%) e não pertenciam (78,55%) a área de abrangência do Departamento Regional de Saúde do qual Campinas faz parte. O fármaco mais utilizado nas injeções intravítreas foi o bevacizumabe (79,38%), o principal regime de tratamento foi o pro re nata (90,27%) e a principal grupo de patologia indicativa de tratamento foi o edema macular (60,12%), sendo 48,25% desses de etiologia diabética. A média de injeções foi de 3,83/paciente, sendo o grupo de neovascularização macular o de maior mediana com 5 injeções/paciente e o esquema pro re nata o regime de tratamento com menor mediana, 3 injeções/paciente. A adesão ao tratamento associou-se a patologia do paciente, sendo as menores taxas de adesão as dos grupos com edema macular (52,24%) e neovascularização macular (49,48%). Conclusões: O presente estudo avaliou o perfil epidemiológico e clínico dos pacientes submetidos a terapia antiangiogênica em hospital público de alta complexidade, o que é fundamental para melhor conhecimento da demanda de serviço oftalmológico de referência no Brasil e possibilita, a partir da análise dos resultados funcionais e perfil de adesão dos usuários, otimizar as indicações e alavancar os benefícios de terapia intravítrea.
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ABSTRACT A 71-year-old woman presented a non-arteritic anterior ischemic optic neuropathy in an optic nerve with previously registered superonasal peripapillary myelinated nerve fibers. Her past medical history was significant for controlled systemic hypertension, hyperlipidemia, and diabetes mellitus. The physiologic cup was absent in both optic discs. Non-arteritic anterior ischemic optic neuropathy mainly affected the temporal and inferior sectors of the peripapillary retinal nerve fiber layer, as could be demonstrated by retinal nerve fiber layer optical coherence tomography and optic disc optical coherence tomography angiography. Unlike other published reports, just a slight regression of the myelinated nerve fibers was observed after 1 year of follow-up. This occurred because ischemia mainly affected the temporal and inferior peripapillary sectors, whereas myelinated nerve fibers were superonasal to the optic disc.
RESUMO Uma mulher de 71 anos de idade apresentou neuropatia óptica isquêmica anterior não arterítica no nervo óptico com fibras nervosas peripapilares mielinizadas previamente registradas. Seu histórico médico foi significativo para hipertensão arterial sistêmica controlada, hiperlipidemia e diabetes mellitus. Em ambos os discos ópticos, a tacícula fisiológica esteve ausente. A neuropatia óptica isquêmica anterior não arterítica afetou principalmente os setores temporal e inferior da camada de fibras nervosas da retina peripapilar, como demonstrado pela tomografia de coerência óptica da camada de fibras nervosas da retina e pela angiotomografia de coerência óptica do disco óptico. Ao contrário de outros relatórios publicados, apenas uma ligeira regressão das fibras nervosas mielinizadas foi observada após um ano de acompanhamento. Isto pode ser explicado pelo fato da isquemia ter afetado principalmente os setores temporal e inferior peripapilares, enquanto as fibras nervosas de mielina eram nasal superior ao disco óptico.
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We report the findings observed in a young woman with ocular syphilis complicated with retinal and disc neovascularization successfully treated with intravitreal bevacizumab. Fluorescein angiography revealed in both eyes intense hyperfluorescence at the level of the disc, multifocal venous wall staining, multifocal paravenous leakage, multiple peripheral saccular venular dilations, diffuse retinal and macular edema, and retinal and disc neovascularization. There was no evidence of retinal ischemia in both eyes. After antibiotic and corticosteroid treatment, the neovascularization persisted in both eyes. Three consecutive doses of intravitreal bevacizumab were administered, with total regression of the retinal and disc neovascularization. Disc and retinal neovascularization along with nonocclusive retinal vasculitis may be a form of presentation of ocular syphilis. Combination of specific treatment, oral corticosteroids, and intravitreal bevacizumab may be useful for treating this clinical manifestation.
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BACKGROUND: Papilledema is the main ocular finding in patients with idiopathic intracranial hypertension (IIH) although several chorioretinal abnormalities may also occur and contribute to visual loss. The purpose of this paper is to describe two cases of chorioretinal abnormalities associated with idiopathic intracranial hypertension: one with choroidal folds and another with polypoidal choroidal vasculopathy, an extremely unusual ocular complication in the disease. CASE PRESENTATION: Case 1: A 47-year-old woman previous diagnosed with idiopathic intracranial hypertension treated with weight loss and acetazolamide that over the following 6 months had optic disc edema gradually resolved. The patient was follow-up for a period of 10 years and the papilledema disappeared, but choroidal folds remained unchanged. Case 2: A 61-year-old female patient was seen as a follow-up examination of a 5-year history of IIH that presented with papilledema. The patient was asymptomatic but fundoscopy evaluation revealed a yellowish white peripapillary subretinal nodular lesion temporally in OD. Multimodal imaging studies were made, and the patient was diagnosed with a rare and just recent described association of IIH and polypoidal choroidal vasculopathy. CONCLUSION: Papilledema, RNFL and retinal ganglion cell loss are the most common structural complications of IIH, but chorioretinal complications are important findings and should be carefully evaluated in such patients. Awareness of such occurrence and the use of appropriated clinical and multimodal imaging studies are of great importance for its early detection, leading to proper treatment and prevention of further visual loss.
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Diabetes is a disease that leads to proliferative diabetic retinopathy (PDR), which is associated with an increase of new vessels formation due to an overexpression of angiogenic factors, such as angiopoietin 2 (ANGPT2). The aim of this work was to design a siRNA targeting ANGPT2 to decrease the retinal neovascularization associated with PDR. Adult male Wistar rats weighing 325-375 g were used. Diabetes was induced by a single dose of streptozotocin (STZ, 60 mg/kg i.p.). The siRNAs were designed, synthesised, and administered intravitreally at the beginning of diabetes induction (t0), and after 4 weeks of diabetes evolution (t4), subsequently evaluated the retinal neovascularization (junctions and lacunarity) and ANGPT2 expression in the retina by RT-PCR, after 4 weeks of the siRNAs administration. The results showed that the administration of STZ produced significant increases in blood glucose levels, retinal neovascularization (augmented junctions and lower lacunarity), and ANGPT2 expression, while the administration of the ANGPT2-siRNAs at different groups (t0 and t4) reduces the junctions and increases the lacunarity in diabetic rats. Therefore, we conclude that the administration of siRNAs targeting ANGPT2 could be an option to decrease the retinal neovascularization associated with PDR and halt the progression of blindness caused by diabetes.
Assuntos
Diabetes Mellitus Experimental , Retinopatia Diabética , Neovascularização Retiniana , Angiopoietina-2/genética , Animais , Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/genética , Masculino , Neovascularização Patológica/genética , RNA Interferente Pequeno/farmacologia , Ratos , Ratos Wistar , Retina/metabolismo , Neovascularização Retiniana/complicações , Neovascularização Retiniana/genética , Neovascularização Retiniana/metabolismo , EstreptozocinaRESUMO
ABSTRACT We conducted retinal neovascularization under subfoveal fibrotic nodule for Coats disease by using optic coherence tomography-angiography before and after ranibizumab treatment. Our patient was an 8-year-old boy who was referred with suspicious left retinal mass. His visual acuity was 20/400 in the left eye and 20/20 in the right eye at the time of admission. Posterior segment evaluation of the left eye revealed telengiectatic vessels at the inferotemporal region of the peripheral retina with hard exudates around the optic disc and macula typical for Coats disease. His optic coherence tomography revealed a subfoveal fibrotic nodule after ranibizumab injections and laser photocoagulation treatment. The optic coherence tomography-angiography results revealed neovascularization under the subfoveal nodule at the superficial vascular complex layer. After 3 intravitreal ranibizumab injections, his neovascularization regressed on optic coherence tomography-angiography and his visual acuity improved. To the best of our knowledge, this is the first report demonstrating neovascularization under the subfoveal fibrotic nodule in Coats disease on the basis of comparative with the help of optic coherence tomography-angiography before and after the treatment.
RESUMO Demonstramos uma neovascularização da retina sob o nódulo fibrótico subfoveal na doença de Coats com a ajuda da Angiotomografia de Coerência Óptica (OCT-A) antes e após o tratamento com ranibizumabe. Paciente do sexo masculino de 8 anos foi encaminhado com suspeita de massa retiniana no olho esquerdo. A acuidade visual foi de 20/400 no olho esquerdo e de 20/20 no olho direito. A avaliação do segmento posterior do olho esquerdo revelou vasos telengiectáticos na região inferotemporal da retina periférica e exsudados duros em torno do disco óptico e mácula típica da doença de Coats. A angiotomografia de coerência óptica apresentou nódulo fibrótico subfoveal após injeções de ranibizumabe e tratamento com fotocoagulação a laser. A angiotomografia de coerência óptica mostrou neovascularização sob o nódulo subfoveal na camada superficial do complexo vascular. Após três injeções de ranibizumabe intravítreo, a neovascularização regrediu na angiografia por tomografia de coerência óptica e a acuidade visual melhorou. onde sabemos, este é o primeiro relato a mostrar neovascularização sob nódulo fibrótico subfoveal na Doença de Coats com a ajuda da angiografia por tomografia de coerência óptica antes e após o tratamento.
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Abstract Objective: The primary objective of the study is to evaluate, in a population in the state of Bahia, Brazil, the impact of ranibizumab in best-corrected visual acuity of patients with macular disease and macular edema. Methods: This study did a retrospective and observational assessment visual acuity of the group of patients followed at the Professor Edgard Santos University Hospital and Oftalmodiagnose Eye Hospital in 2011 and 2012 in a real life context. Results: The impact on sample patientes post-treatment demonstrated favorable outcome with an increase in visual acuity of 32%, which means improvement of more than one line in the snellem chart. Conclusion: Improvement in visual acuity of this group was observed from baseline to the end of follow up in a real-life context.
Resumo Objetivo: O objetivo principal do estudo é avaliar, em uma população no estado da Bahia, o impacto do ranibizumab na acuidade visual melhor corrigida de pacientes com doença macular e edema macular. Métodos: Para isso, fizemos uma avaliação retrospectiva e observacional da acuidade visual do grupo de pacientes seguidos no Hospital Universitário Professor Edgard Santos e Oftalmodiagnose Hospital de Olhos em 2011 e 2012 em um contexto de vida real. Resultados: O estudo demonstrou desfecho favorável com aumento da acuidade visual de 32%, o que significa melhora de mais de uma linha no quadro snellem. Conclusão: A melhora da acuidade visual desse grupo foi observada desde o início até o final do seguimento em um contexto da vida real.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Acuidade Visual/efeitos dos fármacos , Edema Macular/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Ranibizumab/uso terapêutico , Degeneração Macular/tratamento farmacológico , Estudos Retrospectivos , Estudo ObservacionalRESUMO
Background: The great diversity of molecules found in spider venoms include amino acids, polyamines, proteins and peptides, among others. Some of these compounds can interact with different neuronal receptors and ion channels including those present in the ocular system. To study potential toxicity and safety of intravitreal injection in rabbits of LyeTx I b, a synthetic peptide derived from the toxin LyeTx I found in venom from the spider Lycosa eritrognatha and to evaluate the angiogenic activity on a CAM model. Methods: ARPE-19 cells were treated with LyeTx I b (0.36; 0.54; 0.72; 2.89; 4.34 or 9.06 M). In this study, New Zealand rabbits were used. LyeTx I b (2.89 M) labeled with FITC dissolved in PBS, or only PBS, were injected into vitreous humor. Electroretinogram (ERG) was recorded 1 day before injection and at 7,14 and 28 days post-injection. Clinical examination of the retina was conducted through tonometer and eye fundus after ERG. Eyes were enucleated and retinas were prepared for histology in order to assess retinal structure. CAMs were exposed to LyeTx I b (0.54; 0.72; 2.17 or 2.89 M). Results: ARPE-19 cells exposed to LyeTx I b showed cell viability at the same levels of the control. The fluorescence of LyeTx I b labeled with FITC indicated its retinal localization. Our findings indicate ERG responses from rats injected in the eye with LyeTx I b were very similar to the corresponding responses of those animals injected only with vehicle. Clinical examination found no alterations of intraocular pressure or retinal integrity. No histological damage in retinal layers was observed. CAM presented reduced neovascularization when exposed to LyeTx I b. Conclusions: Intravitreal injection of LyeTx I b is safe for use in the rabbit eye and prevents neovascularization in the CAM model, at Bevacizumab levels... (AU)
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Animais , Coelhos , Injeções Intravítreas/veterinária , Peptídeos/uso terapêutico , Venenos de Aranha/química , Venenos de Aranha/uso terapêutico , Neovascularização Retiniana/prevenção & controle , Membrana Corioalantoide , Aranhas , Toxinas BiológicasRESUMO
BACKGROUND: The great diversity of molecules found in spider venoms include amino acids, polyamines, proteins and peptides, among others. Some of these compounds can interact with different neuronal receptors and ion channels including those present in the ocular system. To study potential toxicity and safety of intravitreal injection in rabbits of LyeTx I b, a synthetic peptide derived from the toxin LyeTx I found in venom from the spider Lycosa eritrognatha and to evaluate the angiogenic activity on a CAM model. METHODS: ARPE-19 cells were treated with LyeTx I b (0.36; 0.54; 0.72; 2.89; 4.34 or 9.06 µM). In this study, New Zealand rabbits were used. LyeTx I b (2.89 µM) labeled with FITC dissolved in PBS, or only PBS, were injected into vitreous humor. Electroretinogram (ERG) was recorded 1 day before injection and at 7, 14 and 28 days post-injection. Clinical examination of the retina was conducted through tonometer and eye fundus after ERG. Eyes were enucleated and retinas were prepared for histology in order to assess retinal structure. CAMs were exposed to LyeTx I b (0.54; 0.72; 2.17 or 2.89 µM). RESULTS: ARPE-19 cells exposed to LyeTx I b showed cell viability at the same levels of the control. The fluorescence of LyeTx I b labeled with FITC indicated its retinal localization. Our findings indicate ERG responses from rats injected in the eye with LyeTx I b were very similar to the corresponding responses of those animals injected only with vehicle. Clinical examination found no alterations of intraocular pressure or retinal integrity. No histological damage in retinal layers was observed. CAM presented reduced neovascularization when exposed to LyeTx I b. CONCLUSIONS: Intravitreal injection of LyeTx I b is safe for use in the rabbit eye and prevents neovascularization in the CAM model, at Bevacizumab levels. These findings support intravitreal LyeTx I b as a good candidate to develop future alternative treatment for the retina in neovascularization diseases.
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Resumo Objetivo: O objetivo desse trabalho é avaliar o perfil de aplicações intravítreas do Ranibizumab em uma população de adultos atendidos no Instituto Benjamin Constant, no ano de 2015, levando em consideração o efeito sobre a acuidade visual e a espessura macular após tratamento. O objetivo secundário é apresentar as principais indicações desse tipo tratamento no serviço de olhos acima citado. Métodos: Foi realizado um estudo retrospectivo seccional, em indivíduos acima de 20 anos entre os meses de março a agosto de 2015, para analisar a acuidade visual e espessura foveal pré e pós tratamento. A dose do anti-VEGF utilizada foi de 0,05ml por aplicação com intervalo de quatro semanas entre elas. A aferição da acuidade visual assim como o OCT pós tratamento foram realizados em torno de trinta dias após a última aplicação. As análises estatísticas foram feitas com uso do software SPSS versão 21 e o nível de significância estatística foi de 95% com um valor de p <0,05. Resultado: O estudo mostrou que a principal afecção relacionada a esse tratamento foi a retinopatia diabética não proliferativa associada ao edema macular (32,8%). Após o tratamento indicado com Ranibizumab, houve uma melhora da acuidade visual média de 0,70 para 0,59 (logMAR) e uma regressão da espessura macular, visto no OCT, de 408,1µm para 337,2 µm (valor de p <0,05). Conclusão: Pode-se concluir portanto, que o tratamento com Ranibizumab na população estudada contribuiu para uma melhor qualidade de vida dos pacientes, pois a maioria dele apresentou uma melhora estatisticamente significativa na acuidade visual após as aplicações.
Abstract The objective of this work is to evaluate the profile of intravitreal applications of Ranibizumab in a population of adults attended at the Benjamin Constant Institute in the year of 2015, taking into account the effect on visual acuity and macular thickness after the treatment. The secondary objective is to present the main indications of this type of treatment in the eye care mentioned above. A retrospective cross-sectional study was performed in individuals over 20 years of age between March and August of 2015 to analyze visual acuity and foveal thickness before and after treatment. The dose of anti-VEGF used was 0.05 ml per application with an interval of four weeks between them. Visual acuity assessment as well as OCT post treatment were performed around 30 days after the last application. Statistical analyses were performed using SPSS software version 21 and the level of statistical significance was of 95% with a value of p <0.05. The study showed that the main condition related to this treatment was non-proliferative diabetic retinopathy associated with macular edema (32.8%). After treatment indicated with Ranibizumab, there was an improvement in the average visual acuity from 0.70 to 0.59 (logMAR) and a regression of the macular thickness, seen in the OCT, from 408.1μm to 337.2μm (p < 0.05). It can be concluded, therefore, that treatment with Ranibizumab in the studied population contributed to a better quality of life of the patients, since most of them presented a statistically significant improvement in the visual acuity after the applications.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Edema Macular/tratamento farmacológico , Edema Macular/diagnóstico por imagem , Injeções Intravítreas , Ranibizumab/administração & dosagem , Retina/diagnóstico por imagem , Angiofluoresceinografia , Acuidade Visual , Neovascularização Retiniana , Estudos Retrospectivos , Neovascularização de Coroide , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/farmacologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Tomografia de Coerência Óptica , Retinopatia Diabética , Ranibizumab/uso terapêutico , Ranibizumab/farmacologia , Fóvea Central/diagnóstico por imagem , Macula Lutea/diagnóstico por imagem , Degeneração MacularRESUMO
Objetivo: Exponer la experiencia local sobre el tratamiento de las enfermedades retinales con terapias anti factor de crecimiento endotelial vascular (anti-VEGF) y crear conciencia en relación con la atención centrada en el paciente reconociendo el papel de los médicos especialistas en la determinación del tratamiento más apropiado basado principalmente en la evidencia científica, pero también teniendo en cuenta la experiencia y práctica exitosas en el manejo de cada paciente, con base en sus características únicas e individuales. Método: Revisión y comparación de la literatura científica con la experiencia de los autores, en el diagnóstico y tratamiento de las enfermedades que involucran inyecciones intraoculares, haciendo especial énfasis en la degeneración macular relacionada con la edad neo vascular (DMRE-NV), el edema macular diabético (EMD), la retinopatía diabética (RD), edema macular por oclusión venosa de rama de vena central de la retina (ORVR), la oclusión de vena central de la retina (OVCR) y la neo vascularización sub retiniana asociada a miopía patológica (MP). Resultados: la revisión realizada reafirma que tanto cuando hablamos de clases de medicamentos, de algoritmos de tratamiento o de perfiles de paciente, los diferentes agentes de una misma clase terapéutica pueden tener eficacias o perfiles de seguridad variables. Se debe considerar la importancia clínica que representa la valoración adecuada de los resultados pos tratamiento, pero sobre todo, la selección cuidadosa para determinar el agente y esquema más apropiado en la intención de tratar a un paciente. Si bien existen recomendaciones y guías de tratamiento para las patologías, los protocolos en el manejo individualizado y la exposición de estas experiencias de vida real se hacen necesarios, ya que no todos los pacientes ni todas las enfermedades de la retina responden de igual forma a cada agente terapéutico. Conclusión: La efi cacia y seguridad en el uso de las terapias anti-VEGF son aspectos de suma importancia cuando se trata de proporcionar una atención verdaderamente centrada en el paciente. No hay ninguna solución, intervención o alternativa terapéutica que se ajuste a todas las enfermedades oculares complejas, por lo que es importante hacer un balance que considere la evidencia disponible, la experiencia, y las expectativas de los pacientes y tratantes. Esto permitirá acceder a las alternativas terapéuticas adecuadas, en el momento adecuado siempre teniendo en mente los perfiles de eficacia, seguridad, farmacovigilancia activa y los costos asociados a las alternativas terapéuticas utilizadas en el país.
Purpose: To display local experience on treatment for retinal diseases with anti-Vascular Endothelial Growth Factor (anti-VEGF) therapies and to raise awareness regarding patient-centered care, recognizing the role of medical specialists in determining the most appropriate treatment mainly based on scientific evidence, but also considering the successful experience and practice handling each patient, based on their unique and individual characteristics. Method: Review and comparison of scientific literature according to the authors experience to diagnose and treat diseases involving intraocular injections, focusing on Neovascular Age-related Macular Degeneration (NV-AMD), Diabetic Macular Edema (DME), Diabetic Retinopathy (DR), Macular Edema due to Branch Retinal Vein Occlusion (BRVO), Central Retinal Vein Occlusion (CRVO) and Sub-retinal Neovascularization associated with Pathological Myopia (PM). Results: the review confi rms that, when speaking of drug classes, treatment algorithms or patient profi les, diff erent agents of the same therapeutic class can result in variable efficacies or safety profiles. The clinical relevance represented by the adequate assessment of post-treatment results must be considered, but specially, the careful screening to determine the most appropriate agent and regimen in the intention-to-treat a patient. Th ough recommendations and treatment guidelines for pathologies exist, protocols in individualized management and exposure of these real-life experiences are necessary, since not all patients or all retinal diseases respond in the same way to each therapeutic agent. Conclusion: Efficacy and safety using anti-VEGF therapies are extremely important when it comes to providing truly patient-centered care. There is no therapeutic solution, intervention or alternative that fi ts all complex ocular diseases, so it is important to weigh the available evidence, the experience and the expectations of both patients and prescribers. Th is will allow to get access to the appropriate therapeutic alternatives, in a timely manner, always considering the efficacy and safety profiles, active pharmacovigilance and the costs associated with the therapeutic alternatives used locally.
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Doenças Retinianas/terapia , Educação de Pessoas com Deficiência Visual , Oftalmopatias/terapia , Injeções Intraoculares , Fator A de Crescimento do Endotélio Vascular/uso terapêuticoRESUMO
The great diversity of molecules found in spider venoms include amino acids, polyamines, proteins and peptides, among others. Some of these compounds can interact with different neuronal receptors and ion channels including those present in the ocular system. To study potential toxicity and safety of intravitreal injection in rabbits of LyeTx I b, a synthetic peptide derived from the toxin LyeTx I found in venom from the spider Lycosa eritrognatha and to evaluate the angiogenic activity on a CAM model. Methods: ARPE-19 cells were treated with LyeTx I b (0.36; 0.54; 0.72; 2.89; 4.34 or 9.06 µM). In this study, New Zealand rabbits were used. LyeTx I b (2.89 µM) labeled with FITC dissolved in PBS, or only PBS, were injected into vitreous humor. Electroretinogram (ERG) was recorded 1 day before injection and at 7,14 and 28 days post-injection. Clinical examination of the retina was conducted through tonometer and eye fundus after ERG. Eyes were enucleated and retinas were prepared for histology in order to assess retinal structure. CAMs were exposed to LyeTx I b (0.54; 0.72; 2.17 or 2.89 µM). Results: ARPE-19 cells exposed to LyeTx I b showed cell viability at the same levels of the control. The fluorescence of LyeTx I b labeled with FITC indicated its retinal localization. Our findings indicate ERG responses from rats injected in the eye with LyeTx I b were very similar to the corresponding responses of those animals injected only with vehicle. Clinical examination found no alterations of intraocular pressure or retinal integrity. No histological damage in retinal layers was observed. CAM presented reduced neovascularization when exposed to LyeTx I b. Conclusions: Intravitreal injection of LyeTx I b is safe for use in the rabbit eye and prevents neovascularization in the CAM model, at Bevacizumab levels. These findings support intravitreal LyeTx l b as a good candidate to develop future alternative treatment for the retina in neovascularization diseases.(AU)
Assuntos
Animais , Peptídeos , Neovascularização de Coroide , Injeções IntravítreasRESUMO
ABSTRACT Purpose: To evaluate the retinal vascularization process after intravitreal ranibizumab was administered to infants with aggressive posterior retinopathy of prematurity (AP-ROP). Methods: Twenty-six eyes of 13 infants with AP-ROP who received 0.25 mg intravitreal ranibizumab were retrospectively investigated. The patients were evaluated at weekly follow-up visits, and the findings were analyzed after retinal vascularization was complete. Results: The results showed regression in the AP-ROP of all the patients within the first 48-72 h. Average time for complete vascularization of the nasal quadrant (zone II) was postmenstrual week 45 (range 41-56), and vascularization of the temporal quadrant (zone III) was completed in the postmenstrual week 56 (range 50-65). Reactivation was observed in seven patients, on average at postmenstrual week 42; two of these patients underwent additional treatment. Two patients presented with avascular areas in the peripheral retina despite being 1 year old. Conclusion: These results showed that retinal vascularization following intravitreal ranibizumab was completed after a delay in patients with AP-ROP. Further studies are necessary to evaluate when and how vascularization occurs after intravitreal anti-vascular endothelial growth factor treatments.
RESUMO Objetivo: Avaliar o processo de vascularização da retina após injeção intravítrea de ranibizumab aplicada em crianças com retinopatia da prematuridade posterior agressiva (AP-ROP). Métodos: Vinte e seis olhos de 13 crianças com AP-ROP que receberam 0,25 mg de ranibizumab intravítreo foram investigados retrospectivamente. Os resultados foram avaliados após a completa vascularização da retina, observada em acompanhamentos semanais. Resultados: Verificou-se que houve regressão na AP-ROP de todos os pacientes durante as primeiras 48 a 72 horas. Na média, a vascularização do quadrante nasal (zona II) foi concluída na semana 45 pós-menstrual (variação 41-56), enquanto a vascularização do quadrante temporal (zona III) foi concluída na semana 56 pós-menstrual (variação 50-65). Sete pacientes (7/13) apresentaram reativação, que aconteceram em média a 42,14 semanas pós-menstruais, dois pacientes receberam tratamento adicional. Dois pacientes apresentaram áreas avasculares na retina periférica apesar de terem um ano de idade. Conclusões: O presente estudo mostrou que a vascularização da retina após a injeção intravítrea de ranibizumab foi concluída com atraso na AP-ROP. Ensaios clínicos randomizados são necessários para avaliar quando e como a vascularização acontece após tratamentos com injeções intravítreas de anti-VEGF.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Retinopatia da Prematuridade/tratamento farmacológico , Neovascularização Retiniana/tratamento farmacológico , Ranibizumab/uso terapêutico , Recidiva , Recém-Nascido Prematuro , Estudos Retrospectivos , Seguimentos , Idade Gestacional , Inibidores da Angiogênese/uso terapêutico , Injeções IntravítreasRESUMO
We report the case of a patient with congenital toxoplasmosis and submacular hemorrhage caused by a neovascular membrane who underwent an intravitreal injection of C3F8 and bevacizumab, and had a good visual recovery.
Relatamos o caso de uma paciente com toxoplasmose congênita e hemorragia submacular por uma membrana neovascular submetida à injeção intravítrea de C3F8 e bevacizumabe, com boa recuperação visual.
Assuntos
Adolescente , Feminino , Humanos , Injeções Intravítreas/métodos , Hemorragia Retiniana/tratamento farmacológico , Hemorragia Retiniana/etiologia , Toxoplasmose Congênita/complicações , Toxoplasmose Congênita/tratamento farmacológico , Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Meios de Contraste , Fluorocarbonos , Fatores de Tempo , Resultado do Tratamento , Acuidade VisualRESUMO
To report the efficacy of combination therapy (bevacizumab and photocoagulation) in a case of Eales Disease this study has been performed. Bevacizumab (Avastin, 1.25 mg/0.05 ml) was injected intravitreously for the treatment of iris and retinal neovascularization in a 56-year old Hispanic female with photocoagulation treatment to control the recurrence of vitreous haemorrhage. Our results revealed that stabilization of the disease and improvement in visual acuity were achieved without any signs of recurrence. Intravitreal bevacizumab in combination with photocoagulation treatment of ischemic retinal areas may be a good alternative for patients with recurrent vitreous haemorrhage due to Eales disease.
RESUMO
Proliferative sickle cell retinopathy is an uncommon complication in individuals with sickle cell trait (AS). However, the risk for proliferative retinopathy development is increased in patients with AS hemoglobinopathy associated with systemic conditions or ocular trauma. A case of a patient with AS hemoglobinopathy who developed proliferative sickle cell retinopathy after the occurrence of gestational diabetes and pregnancy-induced hypertension is reported. Hemoglobin electrophoresis revealed presence of A2 5.0 percent, S 35.0 percent and A 53.2 percent. The present case emphasizes the importance of evaluating systemic comorbidities in patients with sickle cell trait during pregnancy since sickle cell retinopathy can progress rapidly, as well as the importance of regular eye fundus examination in these patients.
Retinopatia falciforme proliferativa é uma complicação incomum em indivíduos com traço falciforme, havendo, porém, risco aumentado de desenvolver retinopatia proliferativa em pacientes com hemoglobinopatia AS associada a condições sistêmicas ou trauma ocular. Neste artigo será apresentado um caso de paciente com diabetes gestacional, hipertensão arterial sistêmica associada à gravidez e traço falciforme. Eletroforese de hemoglobinas revelou a presença de A2 5,0 por cento, S 35,0 por cento e A 53,2 por cento. Este caso ressalta a importância da avaliação de comorbidades sistêmicas em pacientes com traço falciforme no período gestacional, uma vez que pode ocorrer rápida progressão da retinopatia falciforme, devendo-se realizar também exames regulares do fundo de olho nestes pacientes.
Assuntos
Adulto , Feminino , Humanos , Gravidez , Diabetes Gestacional/diagnóstico , Hipertensão Induzida pela Gravidez/diagnóstico , Doenças Retinianas/complicações , Traço Falciforme/complicações , Doenças Retinianas/diagnóstico , Acuidade Visual/fisiologiaRESUMO
CONTEXT AND OBJECTIVE: Many eye diseases involve increased local levels of vascular endothelial growth factor (VEGF), and there are several therapeutic strategies for them. Thus, the aim of this study was to evaluate the effectiveness and safety of bevacizumab for treating eye diseases involving increased local levels of VEGF, as the assumed pathophysiological mechanism. DATA SOURCES: The following databases were systematically searched for evidence: PubMed, CENTRAL (Cochrane Library), Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs) and reference lists, without language restrictions. Only randomized controlled trials were included. The primary outcome of interest was visual acuity, irrespective of the evaluation method. DATA SYNTHESIS: A total of 667 eyes in nine randomized trials were included. Meta-analysis showed that the proportion of patients with age-related macular degeneration who presented improvements from baseline regarding best-corrected visual acuity was higher among those treated with bevacizumab than among those in the photodynamic therapy group (risk ratio, RR, 0.49; 95 percent confidence interval, CI, 0.31 to 0.78; P = 0.01). CONCLUSIONS: The evidence available demonstrates that bevacizumab alone or combined with other treatments is more effective than other options, including photodynamic therapy, focal photocoagulation and triamcinolone. The use of bevacizumab instead of photodynamic therapy could reduce treatment costs by more than 99 percent and could significantly increase access to treatment. However, long-term studies are still needed in order to reduce uncertainty concerning the safety of this medication for all ocular neovascular diseases in which bevacizumab has the potential to improve visual acuity.
CONTEXTO E OBJETIVOS: Muitas doenças oculares envolvem o aumento dos níveis locais de fator de crescimento do endotélio vascular (FCEV), uma diversidade de estratégias terapêuticas para tais condições. Assim, o objetivo do presente estudo é avaliar a efetividade e a segurança de bevacizumabe para o tratamento de pacientes com doença ocular que envolva o aumento dos níveis locais de FCEV, como mecanismo patofisiológico assumido. FONTE DAS INFORMAÇÕES: Foi realizada busca sistemática pelas evidências disponíveis nas seguintes bases de dados da eletrônicas: PubMed, CENTRAL (The Cochrane Library), Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs), além de referências bibliográficas de estudos relevantes, sem restrições de língua. Foram incluídos apenas ensaios controlados e aleatórios. Acuidade visual, independentemente do método de avaliação, foi considerada o desfecho primário de interesse. SÍNTESE DOS DADOS: Foi incluído um total de 667 olhos testados em nove ensaios clínicos aleatórios. A metanálise demonstrou que a proporção de pacientes com degeneração macular relacionada à idade que melhoraram a acuidade visual foi maior entre os tratados com bevacizumabe do que entre os pacientes em terapia fotodinâmica (risco relativo [RR] 0.49, 95 por cento intervalo de confiança [IC] 0,31 a 0,78, P = 0,01). CONCLUSÕES: A evidência disponível demonstra que bevacizumabe isolado ou combinado com outras terapias é mais eficaz que terapia fotodinâmica, fotocoagulação focal e triancinolona. O uso de bevacizumabe em vez da terapia fotodinâmica poderia reduzir os custos do tratamento em mais de 99 por cento e aumentar significativamente o acesso ao tratamento. Entretanto, o aspecto de segurança do fármaco ainda necessita ser avaliado por estudos em longo prazo com todas as doenças neovasculares em que bevacizumabe tenha o potencial de melhorar acuidade visual.
Assuntos
Humanos , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Edema Macular/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
Este trabalho descreve o caso de uma paciente de 41 anos, com diagnóstico da síndrome da hipertensão intracraniana idiopática (síndrome do pseudotumor cerebral) que desenvolveu perda visual em um dos olhos decorrente de membrana neovascular sub-retiniana envolvendo a região macular. Apesar do tratamento clínico adequado e da realização de fenestração da bainha do nervo óptico com boa regressão do edema de papila não houve resolução da membrana neovascular sub-retiniana mesmo após três injeções intravítreas seqüenciais de bevacizumab. Chamamos a atenção para esta complicação incomum do papiledema, revisamos a literatura a este respeito e discutimos as possíveis causas, bem como a evolução mais comum e as modalidades de tratamento disponíveis para tratamento da membrana neovascular sub-retiniana em pacientes com a síndrome do pseudotumor cerebral.
We report a 41-years-old woman with idiopathic intracranial hyperthension (psedotumor cerebri syndrome) that presented with visual loss in one eye due to subretinal neovascular membrane involving the macular area. Despite the introduction of adequate medical treatment followed by optic nerve sheath fenestration that lead to optic disc edema regression there was no improvement in the subretinal neovascular membrane even after performing three sequential intravitreal injection of bevacizumab. We stress the importance of recognizing this uncommon complication of papilledema and review the literature regarding such an occurrence. We also discuss the possible causes for developing subretinal membrane in papilledema, its most common outcome and the treatment modalities available for managing subretinal neovascular membrane in patients with pseudotumor cerebri syndrome.
RESUMO
A 51-year-old black woman was referred to our Retina Clinic for evaluation of loss of vision in her left eye. She was previously diagnosed with a ruptured retinal arterial macroaneurism (RAM) in the same eye. The ophthalmoscopic examination of the affected eye disclosed a subretinal lesion with some hemorrhage and exudation in the same area previously diagnosed with ruptured RAM. Fluorescein angiography revealed a gradually hyperfluorescent net of vessels located in the subfoveal region, consistent with the diagnosis of subretinal neovascular membrane. In this paper we stress the possibility of subretinal neovascularization following a ruptured RAM, even as a rare event.
Paciente de 51 anos foi encaminhada ao Setor de Retina para avaliação de perda visual no olho esquerdo. A paciente apresentava o diagnóstico prévio de macroaneurisma arterial retiniano (MAR) rôto no referido olho. O exame oftalmológico revelou lesão sub-retiniana hemorrágica associada à exsudação na área previamente diagnosticada com MAR. A angiofluoresceinografia revelou hiperfluorescência gradual localizada na região subfoveal, consistente com o diagnóstico de membrana neovascular sub-retiniana (MNSR). Nosso artigo aponta para a possibilidade, embora rara, da formação de uma MNSR após MAR rôto.