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BACKGROUND: Diabetic retinopathy (DR) stands as the foremost cause of preventable blindness in adults. Despite efforts to expand DR screening coverage in the Brazilian public healthcare system, challenges persist due to various factors including social, medical, and financial constraints. Our objective was to evaluate the quality of images obtained with the AirDoc, a novel device, compared to Eyer portable camera which has already been clinically validated. METHODS: Images were captured by two portable retinal devices: AirDoc and Eyer. The included patients had their fundus images obtained in a screening program conducted in Blumenau, Santa Catarina. Two retina specialists independently assessed image's quality. A comparison was performed between both devices regarding image quality and the presence of artifacts. RESULTS: The analysis included 129 patients (mean age of 61 years), with 29 (43.28%) male and an average disease duration of 11.1 ± 8 years. In Ardoc, 21 (16.28%) images were classified as poor quality, with 88 (68%) presenting artifacts; in Eyer, 4 (3.1%) images were classified as poor quality, with 94 (72.87%) presenting artifacts. CONCLUSIONS: Although both Eyer and AirDoc devices show potential as screening tools, the AirDoc images displayed higher rates of ungradable and low-quality images, that may directly affect the DR and DME grading. We must acknowledge the limitations of our study, including the relatively small sample size. Therefore, the interpretations of our analyses should be approached with caution, and further investigations with larger patient cohorts are warranted to validate our findings.
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During an artificial intelligence (AI)-assisted diabetic retinopathy screening event, we performed a survey on patients´ perceptions on AI. Respondents were individuals with diabetes, mostly followed in primary healthcare with a low education level. While 49.6% of participants said they knew what AI was, only 14% reported good or expert knowledge of AI. The vast majority reported positive feelings towards AI in healthcare. We highlight the importance of understanding patients´ views regarding AI in health in a real-life situation and emphasize the importance of digital education.
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Inteligência Artificial , Aprendizado Profundo , Retinopatia Diabética , Programas de Rastreamento , Humanos , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Programas de Rastreamento/métodos , Adulto , Conhecimentos, Atitudes e Prática em Saúde , Percepção , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Diabetic retinopathy (DR) is a leading cause of blindness. Our objective was to evaluate the performance of an artificial intelligence (AI) system integrated into a handheld smartphone-based retinal camera for DR screening using a single retinal image per eye. METHODS: Images were obtained from individuals with diabetes during a mass screening program for DR in Blumenau, Southern Brazil, conducted by trained operators. Automatic analysis was conducted using an AI system (EyerMaps™, Phelcom Technologies LLC, Boston, USA) with one macula-centered, 45-degree field of view retinal image per eye. The results were compared to the assessment by a retinal specialist, considered as the ground truth, using two images per eye. Patients with ungradable images were excluded from the analysis. RESULTS: A total of 686 individuals (average age 59.2 ± 13.3 years, 56.7% women, diabetes duration 12.1 ± 9.4 years) were included in the analysis. The rates of insulin use, daily glycemic monitoring, and systemic hypertension treatment were 68.4%, 70.2%, and 70.2%, respectively. Although 97.3% of patients were aware of the risk of blindness associated with diabetes, more than half of them underwent their first retinal examination during the event. The majority (82.5%) relied exclusively on the public health system. Approximately 43.4% of individuals were either illiterate or had not completed elementary school. DR classification based on the ground truth was as follows: absent or nonproliferative mild DR 86.9%, more than mild (mtm) DR 13.1%. The AI system achieved sensitivity, specificity, positive predictive value, and negative predictive value percentages (95% CI) for mtmDR as follows: 93.6% (87.8-97.2), 71.7% (67.8-75.4), 42.7% (39.3-46.2), and 98.0% (96.2-98.9), respectively. The area under the ROC curve was 86.4%. CONCLUSION: The portable retinal camera combined with AI demonstrated high sensitivity for DR screening using only one image per eye, offering a simpler protocol compared to the traditional approach of two images per eye. Simplifying the DR screening process could enhance adherence rates and overall program coverage.
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PURPOSE: To assess the safety of injecting human embryonic stem cell retinal pigment epithelial cell dose to treat Stargardt disease. METHODS: In this prospective, Phase I clinical trial, human embryonic stem cell retinal pigment epithelial cells in suspension were injected into the subretinal space in eyes with the worse best-corrected visual acuity (BCVA). After vitrectomy/posterior hyaloid removal, a partial retinal detachment was created and the human embryonic stem cell retinal pigment epithelial cells were administered. Phacoemulsification with intraocular lens implantation was performed in eyes with lens opacity. All procedures were optical coherence tomography-guided. The 12-month follow-up included retinal imaging, optical coherence tomography, visual field/electrophysiologic testing, and systemic evaluation. The main outcome was the absence of ocular/systemic inflammation or rejection, tumor formation, or toxicity during follow-up. RESULTS: The mean baseline BCVAs in the phacoemulsification and no phacoemulsification groups were similar (1.950 ± 0.446 and 1.575 ± 0.303, respectively). One year postoperatively, treated eyes showed a nonsignificant increase in BCVA. No adverse effects occurred during follow-up. Intraoperative optical coherence tomography was important for guiding all procedures. CONCLUSION: This surgical procedure was feasible and safe without cellular migration, rejection, inflammation, or development of ocular or systemic tumors during follow-up.
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Descolamento Retiniano , Epitélio Pigmentado da Retina , Humanos , Epitélio Pigmentado da Retina/patologia , Doença de Stargardt , Estudos Prospectivos , Descolamento Retiniano/patologia , Células-Tronco , Inflamação , Pigmentos da Retina , Tomografia de Coerência ÓpticaRESUMO
BACKGROUND: Cataract surgery with multifocal IOLs could give patients good vision and great satisfaction, at the same time generating high expectations; therefore, its precise indication is essential if we are to reach our goal. The use of optical coherence tomography may be a valuable tool in the screening of macular diseases, which often cannot be detected in routine clinical examinations. This study evaluates the benefit of including spectral domain optical coherence tomography (SD-OCT) in routine preoperative cataract surgery protocols for better case selection in multifocal IOLs. METHODS: Observational and retrospective clinical study that includes patients with an indication for multifocal IOL implantation who underwent retinal fundus exam and SD-OCT examination between 2018 and 2019. The clinical examination with ophthalmoscopy and SD-OCT imaging results were evaluated to observe their influence on the final choice of the lens implanted lens in cataract surgery. RESULTS: 405 eyes from 207 patients with multifocal IOL indication were included. It was found that 220 (54.2%) of all indicated multifocal or trifocal IOLs were in fact implanted. The most important reason for not implanting the indicated IOL was financial, in 116 (59.46%) eyes. The second cause were retinal abnormalities detected by SD-OCT, 63 eyes (15.6%). Those abnormalities included dry age-related macular degeneration (AMD) (50.7%), neovascular AMD (3.1%), vitreomacular adhesion (11.1%), diabetic macular edema (3.1%), epiretinal membrane (ERM) (25.3%) and other macular abnormalities (6.3%). Of the 63 eyes with an abnormal SD-OCT result, 44 (69.8%) were also identified by fundus examination. Nineteen (30.2%) eyes had abnormalities detected only by SD-OCT imaging with a normal clinical exam. CONCLUSIONS: Routine use of SD-OCT imaging may help diagnose pre-existing macular pathologies not identified by clinical exam, helping both physicians and patients choose the ideal IOL individually and has the potential to prevent unsatisfactory functional results.
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Abstract Objectives: Describe ocular findings and its correlation with systemic diseases in Down Syndrome (DS) pediatric patients. Methods: Quantitative and cross-sectional study of prevalence with children aged from 0 to 25 years. Standard ophthalmic examinations performed: visual acuity, slit lamp biomicroscopy, ocular motility, static refraction and indirect ophthalmoscopy. Ocular findings were associated with comorbidities available in pediatric records of patients in FURB Down Syndrome Outpatient clinic, in which they have regular follow-up. Results: A total of 76 patients were evaluated (33 males and 43 females). Of these, 72 patients (94.73%) had ocular abnormalities. Refractive errors were the most prevalent (94.73%), followed by alterations in indirect ophthalmoscopy (40.8%), biomicroscopy (15.8%), ocular motility (15.8%) and epiphora (9.2%). From the refractive changes 13.15% had myopia; 76.31% had hypermetropia and 47.36% had astigmatism. Sytemic abnormalities were observed in 73 children. The most prevalent was thyroid diseases presented in 65.79%, followed by heart disease 61.84%, gastrointestinal disease (15.79%); abdominal hernias (14.4%); respiratory changes (14.4%); genitourinary alterations (10.53%); musculoskeletal alterations (10.53%) and epilepsy (3.95%). There was statically significant association between the presence of myopia and hypothyroidism (p = 0.01); astigmatism and heart diseases (p = 0.003); and astigmatism and genitourinary alterations (p = 0.001). Conclusion: There was a high prevalence of ophthalmologic abnormalities in this study of children with Down Syndrome. Associations between myopia and hypothyroidism, astigmatism and heart diseases, and astigmatism and genitourinary disorders were found. More studies and increase of the sample are necessary to confirm the associations of ophthalmologic abnormalities with most common systemic diseases in this population.
Resumo Objetivos: Descrever as alterações oculares e sua correlação com outras comorbidades em pacientes pediátricos com Síndrome de Down (SD). Métodos: Estudo quantitativo de prevalência com delineamento transversal em crianças de 0 a 25 anos portadoras de SD. Realizados exames oftalmológicos de acuidade visual, biomicroscopia anterior, motilidade ocular, refração estática objetiva ou subjetiva conforme o nível de cooperação do paciente e oftalmoscopia indireta. Os achados foram correlacionados com as comorbidades disponíveis nos prontuários dos pacientes do Ambulatório de Síndrome de Down da FURB, no qual são acompanhados regularmente. Resultados: Foram avaliados 76 pacientes (33 do sexo masculino e 43 do sexo feminino). Dentre esses, 72 pacientes (94,73%) tiveram alterações oculares. Alterações refrativas foram as mais prevalentes (94,73%), seguidas de alterações na oftalmoscopia indireta (40,8%), biomicroscopia (15,8%), motilidade ocular (15,8%) e epífora (9,2%). Das alterações refrativas 13,15% tiveram miopia; 76,31% tiveram hipermetropia e 47,36% tiveram astigmatismo. Na amostra, 73 pacientes possuíam alguma comorbidade. A mais prevalente foi a alteração de tireoide, presente em 65,79% dos pacientes, seguido de alterações cardíacas (61,84%), alterações gastrointestinais (15,79%), hérnias abdominais (14,4%), alterações respiratórias (14,4%), alterações geniturinárias (10,53%), alterações osteomusculares (10,53%) e epilepsia (3,95%). Houve associações significativas entre miopia e hipotireoidismo (p = 0,01); astigmatismo e cardiopatias (p = 0,003); e astigmatismo e alterações geniturinárias (p = 0,001). Conclusão: Houve alta prevalência de alterações oftalmológicas na amostra. Foram encontradas associações entre miopia e hipotireoidismo, astigmatismo e cardiopatias, e astigmatismo e alterações geniturinárias. Mais estudos e aumento da amostra são necessários para confirmar os resultados das associações nessa população.
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PURPOSE: To investigate retinal changes prior to vascular signs in patients with type 2 diabetes without diabetic retinopathy or with mild non proliferative diabetic retinopathy. METHODS: A cross-sectional study was performed in three groups: patients without diabetes, patients with type 2 diabetes without diabetic retinopathy, and patients with diabetes with mild diabetic retinopathy. Analysis of retinal layers was performed objectively with the Cirrus Review Software 6.0 (Carl Zeiss Meditec, Dublin, CA, USA). Macular cube scans were analyzed with regard to: the ganglion cell layer + inner plexiform layer analysis, retinal nerve fiber layer thickness, central subfoveal retinal thickness and average macular thickness. RESULTS: In total, 102 patients were included in this study, of which 28 (27.4%) were classified into control group, 46 (45.0%) classified as diabetic patients with no diabetic retinopathy and 28 (27.4%) classified as mild diabetic retinopathy. Quantitative analysis with the Cirrus software showed that the mean ganglion cell layer and mean retinal nerve fiber layer were thinner in diabetes without diabetic retinopathy group when compared to controls. ANOVA with Bonferroni post test indicated a statistically significant reduction in average retinal thickness in mild diabetic retinopathy group (P = 0.032) compared to control and reduction in ganglion cell layer in diabetes with no diabetic retinopathy (P = 0.039) and mild diabetic retinopathy (P = 0.003). Also indicated reduction in retinal nerve fiber layer in diabetic without diabetic retinopathy and eyes with mild diabetic retinopathy (P < 0.001), compared to controls. CONCLUSIONS: Our study found reduction in thickness of ganglion cell layer and retinal nerve fiber layer in patients with diabetes without diabetic retinopathy, which suggests neuroretinal changes before vascular signs of diabetic retinopathy.
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BACKGROUND AND OBJECTIVE: To investigate the retinal safety of intravitreal (IVT) ziv-aflibercept in rabbits. MATERIALS AND METHODS: Eighteen rabbits were given an IVT injection of ziv-aflibercept (25 mg/mL) or aflibercept (40 mg/mL) and examined by funduscopy, electroretinography (ERG), optical coherence tomography (OCT), light microscopy, and transmission electron microscopy (TEM). Serum, aqueous, and vitreous were obtained afterward for osmolarity analysis. The effect of ziv-aflibercept on human retinal cultured cells (ARPE-19) was assessed by the MTT cell viability assay. RESULTS: All eyes showed normal funduscopy, OCT, and ERG findings at baseline and 24 hours or 7 days after the procedure. Median baseline serum, vitreous, and aqueous osmolarity remained unchanged. Histology and TEM showed no major anatomic signs of toxicity. No cytotoxic effect was observed in ARPE-19 cells exposed to ziv-aflibercept. CONCLUSION: IVT injection ziv-aflibercept at a concentration of 25 mg/mL proved to be safe for the rabbit retina.
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Inibidores da Angiogênese/toxicidade , Receptores de Fatores de Crescimento do Endotélio Vascular/toxicidade , Proteínas Recombinantes de Fusão/toxicidade , Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Animais , Linhagem Celular , Sobrevivência Celular , Avaliação Pré-Clínica de Medicamentos , Eletrorretinografia , Humanos , Injeções Intravítreas , Masculino , Microscopia Eletrônica de Transmissão , Oftalmoscopia , Concentração Osmolar , Coelhos , Retina/fisiopatologia , Epitélio Pigmentado da Retina/ultraestrutura , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
Vital dyes have advanced diagnosis and surgical technique in various specialties, including oncology, gastroenterology and ophthalmology. Intra-operative and diagnostic dyes are finding uses in all areas of ophthalmology, including cornea, cataract, retina, glaucoma, orbit and conjunctiva. We provide a summary of current knowledge of the chemical concepts of vital dyes in ophthalmology. We review the properties of dyes, techniques of application, indications and complications in ocular surgery. Vital dyes represent an expanding area of research, and novel dyes deserve further investigation.
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Corantes/química , Procedimentos Cirúrgicos Oftalmológicos , Oftalmologia/métodos , Coloração e Rotulagem/métodos , Humanos , Período IntraoperatórioRESUMO
Vascularized retinal pigment epithelium detachments (PEDs) are part of the spectrum of neovascular age-related macular degeneration (AMD). These patients with vascularized PEDs are at a higher risk of experiencing severe vision loss. This case report demonstrates the use of a new spectral-domain optical coherence tomography (SD-OCT) algorithm to measure the area and volume of PEDs. When this algorithm was applied to the scans from a patient with a vascularized PED who developed a large submacular hemorrhage while undergoing ranibizumab therapy, the authors found that the algorithm measured an increase in the area and volume of the PED that preceded the macular hemorrhage. Although further studies are needed, the increase in the volume of a PED may serve as a useful predictor of disease progression and the need for more aggressive anti-VEGF therapy.
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Inibidores da Angiogênese/uso terapêutico , Descolamento Retiniano/diagnóstico , Hemorragia Retiniana/diagnóstico , Epitélio Pigmentado da Retina/patologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Algoritmos , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Humanos , Ranibizumab , Estudos Retrospectivos , Tomografia de Coerência ÓpticaRESUMO
PURPOSE: To evaluate the in vivo and in vitro toxicity of sunitinib malate, a multikinase inhibitor molecule. DESIGN: Experimental, Prospective, Controlled. METHODS: Human retinal pigment epithelial (ARPE-19) and human umbilical vein endothelialcells (HUVECS) were used in a culture toxicity test and exposed to different concentrations of sunitinib malate for 18 hours. The HUVECs also were cultured to evaluate the angiogenesis inhibitory effect of sunitinib malate. Fundus photography and angiographic, electrophysiologic, and histopathologic evaluations with light and electron microscopy were performed in two groups of five rabbits each that received different intravitreal concentrations of the drug. Each rabbit received 0.1 ml of sunitinib malate in the right eye (one group with 12.5 mg/ml, the other group with 25 mg/ml); all animals received 0.1 ml of physiologic saline solution in the left eye. After sacrifice, the eyes were enucleated and fixed with modified Karnovsky solution. RESULTS: No toxicity related to sunitinib malate was observed using an in vitro model with the 12.5 and 25 mg/ml solutions in HUVEC and ARPE cell cultures. No toxicity was observed in the in vivo model with 12.5 mg/ml, but light microscopy showed that the 25 mg/ml solution damaged the photoreceptors layer. No functional changes in the electroretinogram were observed in any group. CONCLUSIONS: Sunitinib malate 12.5 mg/ml caused no toxicity in in vivo and in vitro models, but the 25 mg/ml concentration caused retinal changes suggesting toxicity in the in vivo model. Further research with the drug is needed in models of ocular neovascularization.
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Inibidores da Angiogênese/toxicidade , Antineoplásicos/toxicidade , Endotélio Vascular/efeitos dos fármacos , Indóis/toxicidade , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Pirróis/toxicidade , Epitélio Pigmentado da Retina/efeitos dos fármacos , Animais , Contagem de Células , Linhagem Celular , Relação Dose-Resposta a Droga , Eletrorretinografia/efeitos dos fármacos , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Células Fotorreceptoras de Vertebrados/ultraestrutura , Proteínas Tirosina Quinases/antagonistas & inibidores , Coelhos , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/ultraestrutura , Sunitinibe , Veias Umbilicais/citologiaRESUMO
Degeneração Macular Relacionada à Idade (DMRI) exsudativa é a principal causa de perda visual severa em indivíduos acima de 50 anos nos países desenvolvidos. O fator de crescimento endotelial (VEGF) é considerado um dos mais importantes reguladores da angiogênese e da permeabilidade vascular . Drogas com atividade antiVEGF tem se mostrado eficaz em preservar ou melhorar a acuidade visual (AV) ao inibir a permeabilidade vascular e o crescimento neovascular nos pacientes tratados. Este artigo de revisão descreve o atual uso terapêutico das medicações antiVEGF para DMRI exsudativa e fornece uma visão geral do futuro da terapia antiangiogênica.
Neovascular age-related macular degeneration is the leading cause of severe, irreversible vision loss in individuals over 50 years in developed countries. Vascular endothelial growth factor (VEGF) has been shown to play a role in the regulation of choroidal neovascularization and vascular permeability. Anti-VEGF drugs have been shown to preserve or improve visual acuity by inhibiting vascular permeability and arresting the growth of neovascularization in the vast majority of treated patients. This review describes the current literature on the use of this therapeutic approach in the management of neovascular AMD and gives an overview of the future directions.
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Humanos , Proteínas Recombinantes de Fusão/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Aptâmeros de Nucleotídeos/uso terapêutico , Degeneração Macular Exsudativa/tratamento farmacológico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Acuidade Visual/fisiologia , Neovascularização de Coroide/etiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Degeneração Macular Exsudativa/complicações , Degeneração Macular Exsudativa/metabolismo , Bevacizumab/uso terapêutico , Ranibizumab/uso terapêutico , Indazóis/uso terapêutico , Neovascularização Patológica/metabolismoAssuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Glucocorticoides/uso terapêutico , Edema Macular/tratamento farmacológico , Triancinolona Acetonida/uso terapêutico , Bevacizumab , Estudos de Casos e Controles , Feminino , Humanos , Injeções Intravítreas , Macula Lutea/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologiaRESUMO
Purpose. To describe the SD-OCT findings in patients with diffuse unilateral subacute neuroretinitis (DUSN) and evaluate CRT and RNFL thickness. Methods. Patients with clinical diagnosis of DUSN who were submitted to SD-OCT were included in the study. Complete ophthalmologic examination and SD-OCT were performed. Cirrus scan strategy protocols used were 200 × 200 macular cube, optic nerve head cube, and HD-5 line raster. Results. Eight patients with DUSN were included. Mean RNFL thickness was 80.25 µm and 104.75 µm for affected and normal eyes, respectively. Late stage had mean RNFL thickness of 74.83 µm compared to 96.5 µm in early stage. Mean CMT was 205.5 µm for affected eyes and 255.13 µm for normal fellow eyes. Conclusion. RNFL and CMT were thinner in DUSN eyes compared to normal eyes. Late-stage disease had more pronounced thinning compared to early-stage patients. This thinning in RNFL and CMT may reflect the low visual acuity in patients with DUSN.
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The neovascular form of age-related macular degeneration (AMD), called wet-AMD or choroidal neovascularisation, begins with damage to the outer retinal cells and retinal pigment epithelium (RPE), which elicits a cascade of inflammatory and angiogenic responses leading to neovascularisation under the macula. Studies showed that oxidative damage, chronic inflammation of the RPE and complement misregulation work at different steps of this disease. After established neovascularisation, several pro- and antiangiogenic agents start to play an important role. Vascular endothelial growth factors (VEGFs) are the most specific and potent regulators of angiogenesis, which are inhibited by intravitreal injections of ranibizumab, bevacizumab, VEGF Trap, pegaptanib sodium and other agents under investigation. Pigment epithelium-derived factor, on the other hand, shows neuroprotective and antiangiogenic activities. Hepatocyte growth factor (HGF) has a mitogenic effect on a wide range of epithelial and endothelial cells, and it is inhibited by an anti-HGF monoclonal antibody. Platelet-derived growth factor is a potent chemoattractant and mitogen for both fibroblasts and retinal RPE cells, which has been inhibited experimentally by VEGF Trap and human anti-platelet-derived growth factor-D monoclonal antibody. Fibroblast growth factor-2 has pleiotropic effects in different cell and organ systems, and it is blocked by anti-FGF antibodies, with a greater benefit regarding antiangiogenesis when combined treatment with anti-VEGF is performed. Tumour necrosis factor alpha is expressed in the retina and the choroid, and its blockade in choroidal neovascularisation includes the use of monoclonals such as infliximab. This paper reviews the most important cytokines involved in the pathogenesis of wet-AMD, with emphasis on potential combined therapies for disease control.
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Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/metabolismo , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Terapia de Alvo Molecular , Degeneração Macular Exsudativa/tratamento farmacológico , Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Aptâmeros de Nucleotídeos/uso terapêutico , Bevacizumab , Quimioterapia Combinada , Proteínas do Olho/metabolismo , Fator 2 de Crescimento de Fibroblastos/antagonistas & inibidores , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fator de Crescimento de Hepatócito/antagonistas & inibidores , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Infliximab , Injeções Intravítreas , Terapia de Alvo Molecular/métodos , Fatores de Crescimento Neural/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Ranibizumab , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão/uso terapêutico , Serpinas/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismo , Degeneração Macular Exsudativa/metabolismo , Degeneração Macular Exsudativa/fisiopatologiaRESUMO
A patient complained of photopsia and vision loss in the left eye for two days, with visual acuity of 20/32. Right eye was normal. Funduscopy revealed foveal granularity and gray-white lesions in the posterior pole, mainly temporal to the fovea. The lesions (dots and spots), along with a few other areas surrounding them, showed hyperautofluorescence on autofluorescence imaging. Fluorescein angiogram (FA) depicted some early hyperfluorescent dots with late staining. Indocyanine green angiogram (ICGA) showed hypofluorescent lesions in a greater number compared with funduscopy, autofluorescence, and FA. Thirty days later, BCVA was 20/20 in both eyes and the complimentary exams were almost normal, despite an ICGA that showed few small hypofluorescent lesions. This case supports the hypothesis that the choroidal involvement occurs primarily in MEWDS, with secondary involvement of the RPE and the neurosensory retina.
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AIMS: Retinal pharmacotherapy has gained great importance for the treatment of various retinal diseases. An increasing number of drugs have been constantly released into the market, especially for wet age-related macular disease and diabetic macular edema. In this review, the issues concerning the toxicity of current and new classes of drugs are discussed. METHODS: An extensive search of the literature was performed to review various aspects of drug toxicity in retinal pharmacotherapy. The different major classes of drugs, such as corticosteroids, antibiotics, antimetabolites, antineoplastic agents, monoclonal antibodies (mAbs), nonsteroidal anti-inflammatory drugs, enzymes, fibrinolytics, miscellaneous anti-inflammatory and antiangiogenic agents, as well as toxicity unrelated to the drug were identified and discussed. RESULTS: Corticosteroids like fluocinolone, dexamethasone or triamcinolone at low dose cause little damage to the retina, but at high doses signs of toxicity have been well documented. Complications like cataract and glaucoma are quite common with corticosteroids. Aminoglycosides showed differences in the type and doses associated with toxic reactions, thereby the following order of toxicity can be described (from most toxic to least toxic): gentamicin > netilmicin = tobramycin > amikacin = kanamycin. Vancomycin at the usual dose of 1 mg is not toxic to the retina, while further studies are necessary in order to clarify the safety of new-generation quinolones. 5-Fluorouracil has been shown to be nontoxic to the retina after an injection of 2.5 mg in animals. mAbs like ranibizumab and bevacizumab were demonstrated to be safe to the retina in cell culture, animals and humans at high doses. The exact biocompatibility of nonsteroidal anti-inflammatory agents like diclofenac needs further evaluation. Preservatives like benzyl alcohol and changes in pH or osmolarity exert an influence on the toxic effects of intravitreally applied drugs. CONCLUSIONS: A great number of drugs are now used mainly intravitreally without relevant retinal toxicity.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Modelos Animais , Retina/efeitos dos fármacos , Doenças Retinianas/induzido quimicamente , Animais , Avaliação Pré-Clínica de Medicamentos , Humanos , Testes de ToxicidadeRESUMO
AIMS: Experimental retinal research has gained great importance due to the ophthalmic pharmacotherapy era. An increasing number of drugs are constantly released into the market for the treatment of retinal diseases. In this review, animal species, animal models and toxicity assays in retinal research are discussed. METHODS: An extensive search of the literature was performed to review various aspects of the methods of investigation of drug toxicity. The different types of animal species, as well as single animal models available for the evaluation of safety and efficacy of retinal pharmacotherapy, were identified. In addition, a large variety of reported laboratory techniques were critically examined. RESULTS: In vitro studies are the first-line experiments for the development of a new drug for retinal diseases, using retinal pigment epithelial cells and other cell lines. The next step involves in vivo animal studies where nonhuman primates are considered the gold standard. However, cost and legal issues make their use difficult. Mice and rats provide genetically controlled models for investigations. Pigs, dogs and cats represent good large-size animal models, while rabbits are one of the most used species for retinal toxicity evaluations. Various laboratory methods were identified, including light microscopy, electron microscopy, electroretinography and new emerging methods, such as optical coherence tomography and scanning laser ophthalmoscopy for experimental purposes. CONCLUSIONS: A great number of animal species and models are available that simulate retinal diseases and provide experimental data for further human use. Work with animal models should include properly designed toxicity assays to obtain reliable results for safety and efficacy.
Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Modelos Animais , Retina/efeitos dos fármacos , Doenças Retinianas/induzido quimicamente , Testes de Toxicidade/métodos , Animais , Eletrorretinografia/efeitos dos fármacos , Imuno-Histoquímica , Microscopia EletrônicaRESUMO
O objetivo do artigo é apresentar os dados atuais da aplicação de corantes vitais durante cirurgia vitreorretiniana, "cromovitrectomia", bem como uma revisão da literatura atual sobre o assunto no tocante às técnicas de aplicação, indicações e complicações em cromovitrectomia. Um grande número de publicações tem abordado o perfil tóxico da indocianina verde na cromovitrectomia. Dados experimentais mostram uma toxicidade dose-dependente da mesma em várias populações de células retinianas. Novas gerações de corantes incluem: azul tripan, azul patente, acetato de triancinolona, infracianina verde, fluoresceína sódica, azul de bromofenol, acetato de fluorometolona e azul brilhante. Novos instrumentos podem permitir um corar seletivo de estruturas durante a vitrectomia. Este artigo mostra que o campo da cromovitrectomia está em plena expansão de pesquisas. Os corantes de primeira linha são a indocianina verde, infracianina verde e o azul brilhante. Azul patente, azul de bromofenol e azul tripan surgem como novos adjuvantes para melhor observação da membrana epirretiniana. Demais corantes que surgiram merecem maior investigação.
The aim of this article is to present the current data with regard to the application of vital dyes during vitreoretinal surgery, "chromovitrectomy", as well as to overview the current literature regarding the properties of dyes, techniques of application, indications and complications in chromovitrectomy. A large body of published research has recently addressed the toxicity profile of indocyanine green for chromovitrectomy. Experimental data demonstrate dose-dependent toxicity of indocyanine green to various retinal cells. Newer generation vital dyes for chromovitrectomy include trypan blue, patent blue, triamcinolone acetonide, infracyanine green, sodium fluorescein, bromophenol blue, fluorometholone acetate and brilliant blue. Novel instruments may enable a selective painting of preretinal tissues during chromovitrectomy. This review suggests that the field of chromovitrectomy represents an expanding area of research. The first line agents for internal limiting membrane staining in chromovitrectomy are indocyanine green, infracyanine green, and brilliant blue. Patent blue, bromophenol blue and trypan blue arose as outstanding biostains for visualization of epiretinal membranes. Novel dyes available for chromovitrectomy deserve further investigation.
Assuntos
Humanos , Corantes , Vitrectomia/métodos , Corantes/química , Corantes/classificação , Corantes/toxicidadeRESUMO
PURPOSE: To investigate the retinal biocompatibility of six novel vital dyes for chromovitrectomy. METHODS: An amount of 0.05 mL of 0.5% and 0.05% light green (LG), fast green (FG), Evans blue (EB), brilliant blue (BriB), bromophenol blue (BroB), or indigo carmine (IC) was injected intravitreally in the right eye, whereas in the left eye balanced salt solution was applied for control in rabbits' eyes. Clinical examination, fluorescein angiography, histology with light microscopy, and transmission electron microscopy were performed after 1 and 7 days. Retinal cell layers were evaluated for morphologic alterations and number of cells. The electroretinographic changes were assessed at baseline, 24 hours and 7 days. RESULTS: Fluorescein angiography disclosed hypofluorescent spots only in the 0.5% EB group. Light microscopy and transmission electron microscopy disclosed slight focal morphologic changes in eyes exposed to 0.05% IC, FG, BriB, similar to the control at 1 and 7 days. In the lower dose groups, EB, LG, and BroB caused substantial retinal alterations by light microscopy. At the higher dose, BroB and EB produced diffuse cellular edema and vacuolization within the ganglion cells, bipolar cells, and photoreceptors. FG and IC at 0.5% caused slight retinal alterations similar to balanced salt solution injection. LG at 0.5% caused diffuse vacuolization of bipolar cells after 1 and 7 days. Injection of 0.5% EB caused a significant decrease in neuroretinal cell counts in comparison to control eyes in the 7-day examination (P < 0.05). Electroretinography revealed intermittent prolonged latency and decreased amplitude in eyes injected with 0.5% EB, LG, BriB, and BroB, while at the lower dose, only LG and EB induced few functional changes. CONCLUSION: The progressive order of retinal biocompatibility, from safest to most toxic, was IC, FG, BriB, BroB, LG, EB.