RESUMO
PURPOSE OF REVIEW: Prevention and management of postcataract endophthalmitis remain quite relevant for anterior segment and vitreoretinal surgeons. Although the Endophthalmitis Vitrectomy Study, published in 1996, remains the only level 1 evidence for the management of postcataract endophthalmitis, recent advances have resulted in an evolution of practice patterns. The aim of this review is to summarize the literature regarding postcataract endophthalmitis with a focus on the last 18 months. RECENT FINDINGS: The IRIS registry indicates the rates of endophthalmitis are decreasing in the United States, and the outcomes appear to be improving. Intracameral moxifloxacin has become more widely accepted and intracameral vancomycin has been shown to be associated with retinal vasculitis. The role of systemic antibiotics and vitrectomy is unclear and practice patterns vary widely. SUMMARY: Although practice patterns vary, prevention and treatment of endophthalmitis after cataract surgery continues to improve. More uniform guidelines regarding surgical and medical therapy are necessary but the standard of prompt referral to a vitreoretinal specialist for immediate intravitreal antibiotics remains the most important intervention in the management of postcataract endophthalmitis.
Assuntos
Extração de Catarata/efeitos adversos , Endoftalmite/etiologia , Infecções Oculares Bacterianas/etiologia , Antibacterianos/administração & dosagem , Implantes de Medicamento , Endoftalmite/prevenção & controle , Infecções Oculares Bacterianas/prevenção & controle , Humanos , Moxifloxacina/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Vancomicina/administração & dosagem , Vitrectomia , Corpo Vítreo/efeitos dos fármacosRESUMO
PURPOSE: Investigate the potential application of corosolic acid (CA) in the treatment of diseases causing retinal neovascularization. METHODS: CA cytotoxicity effect was evaluated in ARPE-19 cells by sulforhodamine B colorimetric method, and antiangiogenic activity was studied using chorioallantoic membrane (CAM) assay. An amount of 0.01 mL of CA formulations at 5, 10 and 25 µM was injected in the right eyes of Wistar rats, and the contralateral eyes received the vehicle to verify the safety of ophthalmic use. Electroretinography (ERG) was performed before, 7 and 15 days after CA administration. Animals were killed on the 15th day, and the histological analysis of retina was carried out under light microscopy. RESULTS: CA did not present cytotoxicity at concentrations below 35.5 µM after 48 h of treatment. The antiangiogenic activity was confirmed by CAM assay, since CA (range from 5 to 25 µM) induced a significant reduction in vascularity without any signs of toxicity. ERG recordings and histological evaluation did not show any signs of retinal toxicity. CONCLUSIONS: CA was effective in reducing vascularity in a CAM model and was found to be safe for potential ophthalmic use.
Assuntos
Inibidores da Angiogênese/administração & dosagem , Retina/efeitos dos fármacos , Triterpenos/administração & dosagem , Inibidores da Angiogênese/toxicidade , Animais , Linhagem Celular , Membrana Corioalantoide/irrigação sanguínea , Eletrorretinografia/efeitos dos fármacos , Injeções Intravítreas , Masculino , Neovascularização Patológica/tratamento farmacológico , Ratos , Ratos Wistar , Epitélio Pigmentado da Retina/efeitos dos fármacos , Triterpenos/toxicidade , Corpo Vítreo/efeitos dos fármacosRESUMO
ABSTRACT Purpose: We aimed to evaluate the safety of single intravitreal injection of each of two concentrations of 0.1 ml of sunitinib (1 and 10 mg/ml), 0.1 ml of a drug-free dispersion containing solid lipid nanoparticles, and 0.1 ml of a drug-free dispersion containing polymeric nanocapsules for analyzing the possible toxic effects using electrophysiology and histology in albino rabbit retina. Methods: We conducted an experimental controlled study of 20 eyes of albino rabbits. Intravitreal injections of each specific agent were applied to one eye per rabbit in each 5-rabbit group, while the contralateral eyes received no treatment and were used as controls. Results: We noted no electroretinographic changes in the sunitinib (1 and 10 mg/ml) or in solid lipid nanoparticles groups. However, we observed significant abnormalities in ocular morphology and in the electroretinogram in the nanocapsules group. At the histological level, only the nanocapsules group demonstrated abnormal changes, including severe edema and cytoplasmic vacuole formation. Conclusions: While nanocapsules intravitreal injections indicated retinal toxic effects, sunitinib and solid lipid nanoparticles intravitreal injections were not toxic to the retina. Our results suggest that a sunitinib preparation with solid lipid nanoparticles for controlled release may offer a significant therapeutic approach for vasoproliferative ocular disease.
RESUMO Objetivos: O presente estudo teve por objetivo avaliar a segurança da injeção intravítrea de 0,1 ml de sunitinibe em duas concentrações (1 mg/ml e 10 mg/ml), 0,1 ml de dispersão contendo nanopartículas lipídicas sólidas sem droga e 0,1 ml de dispersão contendo nanocápsulas poliméricas livre de drogas analisando os possíveis efeitos tóxicos à retina de coelhos albinos detectados pela eletrofisiologia e histologia por microscopia óptica. Métodos: Um estudo controlado experimental foi realizado com 20 olhos de coelhos albinos. Foram realizadas injeções intravítrea de duas concentrações diferentes de sunitinibe, uma dispersão contendo nanopartículas lipídicas sólidas e uma dispersão contendo nanocápsulas. O olho contralateral não recebeu tratamento e foi utilizado como controle. Resultados: Não foram observadas alterações eletrorretinográficas nos grupos do sunitinibe (1 mg/ml e 10 mg/ml) e no grupo das nanopartículas lipídicas sólidas. No grupo das nanocápsulas, houve alterações significativas tanto na morfologia, quanto na amplitude e tempo das ondas do eletrorretinograma. Ao estudo histológico, somente o grupo das nanocápsulas apresentou alterações degenerativas (núcleos tumefeitos) com acentuado edema e formação de vacúolos citoplasmáticos, sugerindo toxidade retiniana. Conclusões: As injeções intravítreas de sunitinibe e nanopartículas lipídicas sólidas não foram tóxicas para a retina. No entanto, nanocápsulas mostraram ser tóxicas para a retina. Sendo assim, a possibilidade de poder combinar o potencial de uma droga que possui a capacidade de inibir duas importantes vias da angiogênese, às vantagens de liberação controlada das nanopartículas lipídicas sólidas, pode ser um importante recurso terapêutico para doenças vasoproliferativas oculares.
Assuntos
Animais , Ratos , Retina/efeitos dos fármacos , Corpo Vítreo/efeitos dos fármacos , Injeções Intravítreas , Sunitinibe/farmacologia , Eletrorretinografia , Nanocápsulas , NanopartículasRESUMO
PURPOSE: We aimed to evaluate the safety of single intravitreal injection of each of two concentrations of 0.1 ml of sunitinib (1 and 10 mg/ml), 0.1 ml of a drug-free dispersion containing solid lipid nanoparticles, and 0.1 ml of a drug-free dispersion containing polymeric nanocapsules for analyzing the possible toxic effects using electrophysiology and histology in albino rabbit retina. METHODS: We conducted an experimental controlled study of 20 eyes of albino rabbits. Intravitreal injections of each specific agent were applied to one eye per rabbit in each 5-rabbit group, while the contralateral eyes received no treatment and were used as controls. RESULTS: We noted no electroretinographic changes in the sunitinib (1 and 10 mg/ml) or in solid lipid nanoparticles groups. However, we observed significant abnormalities in ocular morphology and in the electroretinogram in the nanocapsules group. At the histological level, only the nanocapsules group demonstrated abnormal changes, including severe edema and cytoplasmic vacuole formation. CONCLUSIONS: While nanocapsules intravitreal injections indicated retinal toxic effects, sunitinib and solid lipid nanoparticles intravitreal injections were not toxic to the retina. Our results suggest that a sunitinib preparation with solid lipid nanoparticles for controlled release may offer a significant therapeutic approach for vasoproliferative ocular disease.
Assuntos
Injeções Intravítreas , Retina/efeitos dos fármacos , Sunitinibe/farmacologia , Corpo Vítreo/efeitos dos fármacos , Animais , Eletrorretinografia , Nanocápsulas , Nanopartículas , CoelhosRESUMO
PURPOSE: Intravitreal anti-vascular endothelial growth factor agents have been shown to reduce diabetic retinopathy (DR) progression; data on the effects of intravitreal corticosteroids on modifying disease severity are limited. This study evaluates the long-term effect of intravitreal dexamethasone implant (DEX) on the severity and progression of non-proliferative DR (NPDR). METHODS: This was a retrospective cohort study. Sixty eyes from 60 consecutive patients with NPDR and diabetic macular edema (DME) treated with dexamethasone implant (DEX group) and 49 eyes from consecutive 49 patients without DME requiring observation only. Fundus angiography images from baseline and after 24 months were graded by two masked assessors into mild, moderate and severe NPDR and PDR, according to the ETDRS classification. Patients were followed up 1-3 and 4-6 months after each DEX implant. Re-treatment with DEX implant was on a pro re nata basis. Records were reviewed for performance of panretinal photocoagulation. Main outcome was as follows: change of DR ≥ 1 grade and progression to proliferative diabetic retinopathy (PDR). RESULTS: Three eyes (5%) in the DEX group and 43 (87.8%) eyes in the control group progressed to PDR (P < 0.0001). Twenty-five eyes (41.7%) in the DEX group but none in the control group demonstrated an improvement in DR severity (P < 0.0001). CONCLUSION: This study provides the first long-term evidence that DEX implant has the potential to not only delay progression of DR and PDR development, but may also improve DR severity over 24 months. Better understanding of the effects of corticosteroids will help guide its use in the treatment pathway of DR.
Assuntos
Dexametasona/administração & dosagem , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/patologia , Retina/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Dexametasona/efeitos adversos , Retinopatia Diabética/fisiopatologia , Progressão da Doença , Implantes de Medicamento , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Retina/fisiopatologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Acuidade Visual/efeitos dos fármacos , Corpo Vítreo/efeitos dos fármacosRESUMO
Etoposide-loaded poly(lactic-co-glycolic acid) implants were developed for intravitreal application. Implants were prepared by a solvent-casting method and characterized in terms of content uniformity, morphology, drug-polymer interaction, stability, and sterility. In vitro drug release was investigated and the implant degradation was monitored by the percent of mass loss. Implants were inserted into the vitreous cavity of rabbits' eye and the in vivo etoposide release profile was determined. Clinical examination and the Hen Egg Test-Chorioallantoic Membrane (HET-CAM) method were performed to evaluate the implant tolerance. The original chemical structure of the etoposide was preserved after incorporation in the polymeric matrix, which the drug was dispersed uniformly. In vitro, implants promoted sustained release of the drug and approximately 57% of the etoposide was released in 50 days. In vivo, devices released approximately 63% of the loaded drug in 42 days. Ophthalmic examination and HET-CAM assay revealed no evidence of toxic effects of implants. These results tend to show that etoposide-loaded implants could be potentially useful as an intraocular etoposide delivery system in the future.
Assuntos
Implantes de Medicamento/metabolismo , Etoposídeo/metabolismo , Ácido Láctico/metabolismo , Ácido Poliglicólico/metabolismo , Corpo Vítreo/metabolismo , Animais , Galinhas , Implantes de Medicamento/administração & dosagem , Implantes de Medicamento/química , Etoposídeo/administração & dosagem , Etoposídeo/química , Injeções Intravítreas , Ácido Láctico/administração & dosagem , Ácido Láctico/química , Masculino , Ácido Poliglicólico/administração & dosagem , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos , Corpo Vítreo/efeitos dos fármacosRESUMO
BACKGROUND: Drug ocular toxicity is a field that requires attention. Clindamycin has been injected intravitreally to treat ocular toxoplasmosis, the most common cause of eye posterior segment infection worldwide. However, little is known about the toxicity of clindamycin to ocular tissues. We have previously showed non intraocular toxicity in rabbit eyes of poly(lactic-co-glycolic acid) (PLGA) implants containing clindamycin hydrochloride (CLH) using only clinical macroscotopic observation. In this study, we investigated the in vivo biocompatibility of CLH-PLGA implants at microscotopic, cellular and molecular levels. METHODS: Morphology of ARPE-19 and MIO-M1 human retinal cell lines was examined after 72 h exposure to CLH-PLGA implant. Drug delivery system was also implanted in the vitreous of rat eyes, retinal morphology was evaluated in vivo and ex vivo. Morphology of photoreceptors and inflammation was assessed using immunofluorescence and real-time PCR. RESULTS: After 72 h incubation with CLH-PLGA implant, ARPE-19 and MIO-M1 cells preserved the actin filament network and cell morphology. Rat retinas displayed normal lamination structure at 30 days after CLH-PLGA implantation. There was no apoptotic cell and no loss in neuron cells. Cones and rods maintained their normal structure. Microglia/macrophages remained inactive. CLH-PLGA implantation did not induce gene expression of cytokines (IL-1ß, TNF-α, IL-6), VEGF, and iNOS at day 30. CONCLUSION: These results demonstrated the safety of the implant and highlight this device as a therapeutic alternative for the treatment of ocular toxoplasmosis.
Assuntos
Clindamicina/administração & dosagem , Clindamicina/química , Ácido Láctico/química , Ácido Poliglicólico/química , Retina/efeitos dos fármacos , Animais , Materiais Biocompatíveis/química , Linhagem Celular , Sistemas de Liberação de Medicamentos/métodos , Células Ependimogliais , Feminino , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Injeções Intravítreas/métodos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Próteses e Implantes , Ratos , Ratos Endogâmicos Lew , Retina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Corpo Vítreo/efeitos dos fármacos , Corpo Vítreo/metabolismoRESUMO
OBJECTIVES: We characterized and compared the in-vivo absorption of topotecan into the aqueous humor after instillation of aqueous and ointment formulations. METHODS: A lanolin/petrolatum ointment was used. New Zealand rabbits were instilled with topotecan solution (6 µg, group A), a single 10 µg dose of topotecan ointment (group B) or with five 10 µg doses of topotecan ointment (group C). Aqueous humor samples were collected at different times. Corneal samples were collected only for group A. Topotecan was quantified using HPLC, and pharmacokinetic parameters were calculated. Acute corneal epithelial toxicity was assessed after multiple instillations of topotecan ointment. KEY FINDINGS: Total topotecan maximum aqueous humor concentration (Cmax ) was 16.1, 69.9 and 287 ng/ml in group A, B and C, respectively. A single dose of topotecan ointment increased threefold and sevenfold the aqueous humor Cmax , and exposure compared to the aqueous formulation. Aqueous humor concentrations from group C eyes were substantially above the cytotoxic concentration for retinoblastoma cells. No corneal toxicity was evident after ointment instillation. CONCLUSIONS: Topotecan penetrated into the aqueous humor of the rabbit eye after multiple doses of an ointment in concentrations pharmacologically active against retinoblastoma cells without eliciting acute toxicity. Topotecan ointment may translate to the clinical treatment of anterior segment disseminated retinoblastoma.
Assuntos
Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/farmacocinética , Retinoblastoma/tratamento farmacológico , Topotecan/administração & dosagem , Topotecan/farmacocinética , Corpo Vítreo/efeitos dos fármacos , Administração Tópica , Animais , Humor Aquoso/efeitos dos fármacos , Córnea/efeitos dos fármacos , Coelhos , Distribuição TecidualRESUMO
This study aimed to report the clinical and structural outcomes of intravitreal ocriplasmin in the treatment of vitreomacular interface disorders in two tertiary centers in Brazil. A retrospective study was performed by reviewing medical records and spectral domain optical coherence tomography (SD-OCT) findings of seven patients who were treated with a single ocriplasmin injection. A total of 57.14% of patients achieved resolution of vitreomacular traction as evidenced by SD-OCT. Regarding our functional results, 87.71% maintained or improved visual acuity after follow-up. To the best of our knowledge, this is the first study reporting initial results of ocriplasmin therapy in Brazil.
Assuntos
Fibrinolisina/uso terapêutico , Fibrinolíticos/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Descolamento do Vítreo/tratamento farmacológico , Idoso , Brasil , Feminino , Fibrinolisina/administração & dosagem , Fibrinolíticos/administração & dosagem , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/administração & dosagem , Estudos Retrospectivos , Aderências Teciduais/tratamento farmacológico , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual/efeitos dos fármacos , Corpo Vítreo/efeitos dos fármacos , Corpo Vítreo/patologia , Descolamento do Vítreo/patologiaRESUMO
ABSTRACT This study aimed to report the clinical and structural outcomes of intravitreal ocriplasmin in the treatment of vitreomacular interface disorders in two tertiary centers in Brazil. A retrospective study was performed by reviewing medical records and spectral domain optical coherence tomography (SD-OCT) findings of seven patients who were treated with a single ocriplasmin injection. A total of 57.14% of patients achieved resolution of vitreomacular traction as evidenced by SD-OCT. Regarding our functional results, 87.71% maintained or improved visual acuity after follow-up. To the best of our knowledge, this is the first study reporting initial results of ocriplasmin therapy in Brazil.
RESUMO O objetivo desse estudo é relatar os resultados iniciais, tanto do ponto de vista funcional quanto anatômico, no tratamento das doenças da interface vítreo-macular com a ocriplasmina em 2 serviços terciários no Brasil. Um estudo retrospectivo foi realizado através de revisão de prontuários, além de análise de achados em tomografia de coerência óptica de domínio espectral (SD-OCT) em 7 pacientes tratados com uma única injeção intravítrea de ocriplasmina. Em nosso estudo 57,14% dos pacientes apresentaram resolução da tração vítreo-macular no SD-OCT. Em relação aos resultados funcionais, 87,71% dos pacientes mantiveram, ou melhoraram sua acuidade visual durante o acompanhamento. Para nosso conhecimento, trata-se do primeiro estudo em nosso país, mostrando resultados iniciais com ocriplasmina em pacientes tratados no Brasil.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fragmentos de Peptídeos/uso terapêutico , Fibrinolisina/uso terapêutico , Descolamento do Vítreo/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Fragmentos de Peptídeos/administração & dosagem , Corpo Vítreo/efeitos dos fármacos , Corpo Vítreo/patologia , Brasil , Acuidade Visual/efeitos dos fármacos , Aderências Teciduais/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Fibrinolisina/administração & dosagem , Descolamento do Vítreo/patologia , Tomografia de Coerência Óptica , Injeções Intravítreas , Fibrinolíticos/administração & dosagemRESUMO
Introducción: La rabdomiólisis es una enfermedad poco frecuente en pediatría. El objetivo es presentar un paciente en el que se desarrolló secundario a una deshidratación hipernatrémica grave tras una diarrea aguda. Caso clínico: Lactante de 11 meses que consultó por fiebre, vómitos, diarrea y anuria. Presentó convulsión tónico-clónica autolimitada. Ingresó en mal estado general, severamente deshidratado, con escasa reactividad. En las pruebas complementarias destacó acidosis metabólica grave, hipernatremia e insuficiencia renal prerrenal. Al tercer día apreció leve hipotonía axial y elevación de creatín fosfokinasa 75.076 UI/l, interpretado como rabdomiólisis. Se inició hiperhidratación y alcalinización sistémica, con buena respuesta clínica y bioquímica, siendo dado de alta sin secuelas motoras. Conclusiones: La hipernatremia grave está descrita como causa rara de rabdomiólisis e insuficiencia renal. En pacientes críticos es importante un alto índice de sospecha de rabdomiólisis y determinación seriada de la creatín fosfokinasa para su detección y tratamiento precoz.
Introduction: Rhabdomyolysis is a rare paediatric condition. The case is presented of a patient in whom this developed secondary to severe hypernatraemic dehydration following acute diarrhoea. Case report: Infant 11 months of age who presented with vomiting, fever, diarrhoea and anuria for 15 hours. Parents reported adequate preparation of artificial formula and oral rehydration solution. He was admitted with malaise, severe dehydration signs and symptoms, cyanosis, and low reactivity. The laboratory tests highlighted severe metabolic acidosis, hypernatraemia and pre-renal kidney failure (Sodium [Na] plasma 181 mEq/L, urine density> 1030). He was managed in Intensive Care Unit with gradual clinical and renal function improvement. On the third day, slight axial hypotonia and elevated cell lysis enzymes (creatine phosphokinase 75,076 IU/L) were observed, interpreted as rhabdomyolysis. He was treated with intravenous rehydration up to 1.5 times the basal requirements, and he showed a good clinical and biochemical response, being discharged 12 days after admission without motor sequelae. Conclusions: Severe hypernatraemia is described as a rare cause of rhabdomyolysis and renal failure. In critically ill patients, it is important to have a high index of suspicion for rhabdomyolysis and performing serial determinations of creatine phosphokinase for early detection and treatment.
Assuntos
Animais , Cobaias , Coelhos , Citosina/análogos & derivados , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Organofosfonatos/administração & dosagem , Organofosfonatos/química , Corpo Vítreo/efeitos dos fármacos , Antivirais/administração & dosagem , Antivirais/química , Química Farmacêutica/métodos , Citosina/administração & dosagem , Citosina/química , Sistemas de Liberação de Medicamentos/métodos , Meia-Vida , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 1/efeitos dos fármacos , Injeções Intravítreas/métodos , Micelas , Pró-Fármacos/administração & dosagem , Pró-Fármacos/química , Retina/efeitos dos fármacos , Retina/virologia , Corpo Vítreo/virologiaRESUMO
PURPOSE: To investigate and compare the mechanism by which lutein-based and synthetic intraocular dyes interact with their target membranes during ophthalmic surgeries. METHODS: Surrogate membrane models were used in order to simulate the different intraocular membranes: internal limiting membrane (ILM), vitreous, anterior capsule (AC), and epiretinal membrane (ERM). Different lutein-based dyes, such as Phacodyne, Retidyne, Retidyne Plus, and Vitreodyne were tested, as well as Trypan Blue (TB), Indocyanine Green (ICG), Brilliant Blue (BB), and Triamcinolone Acetonide (TA). The interactions between the film components occurring at the air-water interface were investigated with surface pressure-area isotherms and polarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS). RESULTS: With the exception of TA and ICG, none of the tested dyes revealed toxicity to the analyzed membranes. The interaction of TA with the vitreous model affected deeply the biointerface structure of the model. A significant condensation of the monolayer is noted when ICG contacted with ILM by the isotherms or even a solubilization of part of the monolayer toward the aqueous subphase. Retidyne Plus may provide the fluidization of the membrane, but maintains intact the structure of proteins present in the model. CONCLUSIONS: The present study demonstrates for the first time that lutein-based dyes interact through a physical mechanism of action with membrane models of structures present in human eye. On the other hand, the chemical interaction of synthetic dyes TA and ICG resulted in an alteration of the membrane models.
Assuntos
Corantes/farmacologia , Olho/efeitos dos fármacos , Luteína/farmacologia , Membranas Artificiais , Soluções Oftálmicas/farmacologia , Câmara Anterior/efeitos dos fármacos , Membrana Basal/efeitos dos fármacos , Membrana Epirretiniana/tratamento farmacológico , Humanos , Modelos Biológicos , Triancinolona Acetonida , Corpo Vítreo/efeitos dos fármacosRESUMO
PURPOSE: To evaluate the in vivo release and ocular toxicity of a tacrolimus-loaded PLGA intravitreal implant. METHODS: Tacrolimus-loaded PLGA implants were inserted into the vitreous cavity of rabbits' eye. At different time points, the vitreous was retrieved and the concentration of tacrolimus released from the implants was determined. Clinical examination was performed to evaluate the implant tolerance. RESULTS: PLGA implants provided controlled and prolonged release of tacrolimus. Approximately 99.97% of the drug was released from the devices at 6 weeks. Ophthalmic examination revealed no evidence of toxic effects of implants. CONCLUSIONS: Tolerance and feasibility of the tacrolimus-loaded PLGA implants, as sustained intraocular drug delivery systems, were demonstrated.
Assuntos
Ácido Láctico/toxicidade , Ácido Poliglicólico/toxicidade , Próteses e Implantes/efeitos adversos , Tacrolimo/toxicidade , Uveíte/tratamento farmacológico , Animais , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/toxicidade , Corioide/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/efeitos adversos , Estudos de Viabilidade , Feminino , Imunossupressores/farmacologia , Imunossupressores/toxicidade , Injeções Intravítreas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos , Retina/efeitos dos fármacos , Esclera/efeitos dos fármacos , Tacrolimo/farmacologia , Corpo Vítreo/efeitos dos fármacosRESUMO
PURPOSE: To evaluate the in vivo release, retinal safety and antiangiogenic effect of a thalidomide-loaded poly-lactide-co-glycolide intravitreal implant. METHODS: New Zealand white rabbits, divided into two groups, I and II, received an intravitreal implant containing or not thalidomide, respectively (n = 12). Intravitreal drug levels were determined during a six-week study period. The potential for toxicity associated with the implants was evaluated by electroretinography and light microscopy (n = 8). Twelve chorioallantoic membranes (CAMs) from chicken eggs were incubated with thalidomide dispersion, implants containing or not thalidomide and vitreous samples and analyzed after two days regarding the percentage of vessels regression. RESULTS: Intravitreal concentrations of thalidomide (ng/ml) were 690.21 ± 177.95, 372.51 ± 185.56, 240.59 ± 133.48, 327.54 ± 169.71, 294.26 ± 142.41 and 465.18 ± 157.51 at 1, 2, 3, 4, 5 and 6 weeks, respectively, after implantation in group I rabbits. No drug was detected in group II samples. Electroretinography and histological evaluations did not show any sign of retina toxicity. There was significant regression of vessels in CAM incubated with thalidomide dispersion, thalidomide-loaded implants and vitreous samples from group I when compared to control. CONCLUSION: The intravitreal implants delivered safe doses of thalidomide that were also effective to induce vessels regression in CAMs.
Assuntos
Inibidores da Angiogênese/administração & dosagem , Membrana Corioalantoide/efeitos dos fármacos , Retina/efeitos dos fármacos , Talidomida/administração & dosagem , Corpo Vítreo/efeitos dos fármacos , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/farmacocinética , Inibidores da Angiogênese/farmacologia , Animais , Embrião de Galinha , Membrana Corioalantoide/irrigação sanguínea , Implantes de Medicamento , Eletrorretinografia , Feminino , Coelhos , Retina/patologia , Solubilidade , Talidomida/efeitos adversos , Talidomida/farmacocinética , Talidomida/farmacologia , Corpo Vítreo/metabolismoRESUMO
PURPOSE: To compare the intravitreal pharmacokinetic profile of a triamcinolone acetonide formulation containing the preservative benzyl alcohol (TA-BA) versus a preservative-free triamcinolone acetonide formulation (TA-PF), and evaluate potential signs of toxicity to the retina. METHODS: A total of 60 New Zealand male white rabbits, divided into two groups, were studied. In the TA-BA group, 30 rabbits received an intravitreal injection of TA-BA (4 mg/0.1 ml) into the right eye. In the TA-PF group, 30 rabbits received an intravitreal injection of TA-PF (4 mg/0.1 ml) into the right eye. The intravitreal drug levels were determined in 25 animals from each group by high-performance liquid chromatography (HPLC). The potential for toxicity associated with the intravitreal triamcinolone injections was evaluated in five randomly selected animals from each group by electroretinography (ERG) and by light microscopy. RESULTS: Median intravitreal concentrations of TA-BA (µg/ml) were 1903.1, 1213.0, 857.8, 442.0, 248.6 at 3, 7, 14, 21 and 28 days after injection. Intravitreal concentrations of TA-PF (µg/ml) were 1032.9, 570.1, 516.6, 347.9, 102.8 at 3, 7, 14, 21 and 28 days after injection. The median intravitreal triamcinolone concentration was significantly higher in the TA-BA compared to the TA-PF group at 7 days post-injection (p < 0.05). There was no significant difference between the two groups in median triamcinolone concentration at the other time points evaluated. There was no evidence of toxic effects on the retina in either group based on ERG or histological analyses. CONCLUSIONS: Following a single intravitreal injection, the median concentration of triamcinolone acetonide is significantly higher in the TA-BA compared to the TA-PF group at 7 days post-injection. No toxic reactions in the retina were observed in either group.
Assuntos
Degeneração Macular/tratamento farmacológico , Retina/efeitos dos fármacos , Triancinolona Acetonida/farmacocinética , Corpo Vítreo/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eletrorretinografia/efeitos dos fármacos , Injeções Intravítreas , Degeneração Macular/metabolismo , Degeneração Macular/fisiopatologia , Masculino , Coelhos , Retina/metabolismo , Retina/fisiopatologia , Triancinolona Acetonida/administração & dosagem , Corpo Vítreo/efeitos dos fármacosRESUMO
Vitreous constitutes about 80% of the volume of the human eye. It is an extended extracellular matrix that is composed of collagen, hyaluronan, and other extracellular matrix molecules, but mostly water. In both health as well as disease, especially diabetic retinopathy (DR), special attention should be drawn to the posterior vitreous cortex and its relation to the retinal surface. The important role of vitreous in the pathogenesis of proliferative DR has already been demonstrated by several experimental and clinical studies. Thus, vitreo-retinal separation by pharmacologic vitreolysis and/or removal by surgical means are appropriate approaches to interrupt the pathogenic contribution of vitreous and prevent progression of diabetic retinopathy to more advanced stages. This review describes various aspects of the molecular morphology and structural anatomy of vitreous and the vitreo-retinal interface, as well as the role of vitreous in the pathophysiology of DR. Lastly, this treatise provides a critical analysis of novel vitreous modulators for pharmacologic vitreolysis in the treatment of DR. Microplasmin is currently the most promising approach to treat vitreoretinal traction by pharmacologic vitreolysis.
Assuntos
Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/fisiopatologia , Fibrinolisina/uso terapêutico , Fibrinolíticos/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Corpo Vítreo/metabolismo , Descolamento do Vítreo , Retinopatia Diabética/cirurgia , Humanos , Retina/efeitos dos fármacos , Retina/fisiopatologia , Retina/cirurgia , Retina/ultraestrutura , Vitrectomia , Corpo Vítreo/efeitos dos fármacos , Corpo Vítreo/patologia , Corpo Vítreo/cirurgia , Descolamento do Vítreo/induzido quimicamente , Descolamento do Vítreo/cirurgiaRESUMO
PURPOSE: To evaluate the ability of novel dyes to stain lens capsule (LC), internal limiting membrane (ILM), epiretinal membrane (ERM), and vitreous. DESIGN: Experimental study in animal and human donor eyes. METHODS: Thirteen dyes, methyl violet, crystal violet, eosin Y, sudan black B, methylene blue, toluidine blue, light green, indigo carmine, fast green, congo red, evans blue, brilliant blue, and bromophenol blue, were injected onto the LC and ILM of enucleated porcine eyes. The vitreous was stained with 2 mL of dyes for 1 minute. Six dyes (indigo carmine, evans blue, fast green, light green, bromophenol blue, and brilliant blue) were selected for experiments in human donor eyes and freshly removed ERM. RESULTS: In the porcine eyes, ILM staining with methylene blue, toluidine blue, indigo carmine, evans blue, bromophenol blue, and fast green was moderate, and methyl violet, crystal violet, brilliant blue, or sudan black resulted in strong staining. Methyl violet, crystal violet, sudan black, toluidine blue, and methylene blue caused histologic damage in porcine retinas. Vitreous examination revealed moderate staining with congo red, crystal violet, fast green, eosin Y, methylene blue, toluidine blue, brilliant blue, bromophenol blue, and methyl violet and strong staining with light green and evans blue. ERMs showed strong staining with 0.5% evans blue and moderate staining with 0.5% light green, fast green, brilliant blue, and bromophenol blue. Evaluation of donor eyes disclosed moderate staining with evans blue, light green, and bromophenol blue and strong staining with 0.5% brilliant blue. Moderate or strong staining of the vitreous occurred with most dyes. LC evaluation showed moderate staining with 0.5% evans blue, fast green, and brilliant blue, whereas 0.5% light green produced strong LC staining. CONCLUSIONS: Brilliant blue shows the best ILM staining, whereas bromophenol blue, evans blue, and light green also stain ILM. Most dyes bind well to LC, vitreous, and ERM.
Assuntos
Membrana Basal/anatomia & histologia , Corantes , Membrana Epirretiniana/diagnóstico , Cápsula do Cristalino/anatomia & histologia , Corpo Vítreo/anatomia & histologia , Animais , Membrana Basal/efeitos dos fármacos , Corantes/toxicidade , Membrana Epirretiniana/tratamento farmacológico , Humanos , Cápsula do Cristalino/efeitos dos fármacos , Coloração e Rotulagem/métodos , Suínos , Doadores de Tecidos , Corpo Vítreo/efeitos dos fármacosRESUMO
PURPOSE: The present study aimed to evaluate an injectable extended-release formulation of prednisolone acetate (PA) for orbital administration. METHODS: Microspheres (MEs) of poly-e-caprolactone (PCL) containing PA were developed by the method of solvent evaporation. The MEs obtained were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), encapsulation efficiency and in vitro release profile. The in vivo release profile was evaluated in rabbits after periocular injection of an aqueous suspension of MEs. The local biocompatibility of the system was verified by histopathologic analysis of the deployment region. RESULTS: After MEs preparation, morphological analysis by SEM showed the feasibility of the employed method. The content of PA encapsulated was 43+/-7% and can be considered as satisfactory. The system characterization by DSC technique, in addition to confirm the system stability, did not indicate the existence of interaction between the drug and the polymer. The in vitro release study showed the prolonged-release features of the developed system. Preliminary in vivo study showed the absence of local toxicity and confirmed the prolonged release profile of PA from MEs, suggesting the viability of the developed system for the treatment of orbital inflammatory diseases. CONCLUSION: The results obtained in this work are relevant and accredit the system developed as a possible alternative to the treatment of inflammatory orbitopathy.
Assuntos
Anti-Inflamatórios/administração & dosagem , Materiais Biocompatíveis/química , Prednisolona/análogos & derivados , Corpo Vítreo/efeitos dos fármacos , Animais , Varredura Diferencial de Calorimetria , Preparações de Ação Retardada/administração & dosagem , Portadores de Fármacos/administração & dosagem , Feminino , Teste de Materiais , Microscopia Eletrônica de Varredura , Microesferas , Poliésteres/administração & dosagem , Prednisolona/administração & dosagem , CoelhosRESUMO
OBJETIVO: O presente estudo objetivou o desenvolvimento e a avaliação de um sistema biodegradável de liberação de fármacos com característica de liberação prolongada, destinado à administração orbitária de acetato de prednisolona (AP). MÉTODOS: O sistema desenvolvido, na forma de microesferas (MEs) de poli-e-caprolactona (PCL) contendo o AP, foi obtido pelo método de evaporação de solvente. As MEs foram caracterizadas por microscopia eletrônica de varredura (MEV), calorimetria diferencial exploratória (DSC), avaliação do teor de encapsulação e pelo perfil de liberação in vitro. O perfil de liberação in vivo foi avaliado em coelhos após administração peribulbar de uma suspensão aquosa das MEs. A biocompatibilidade local do sistema foi verificada por meio de análise histopatológica da região de implantação. RESULTADOS: Após obtenção das MEs, a análise morfológica por MEV mostrou a viabilidade do método de obtenção do sistema. O teor de AP encapsulado foi de 43 ± 7 por cento e pode ser considerado bastante satisfatório. A caracterização do sistema por DSC, além de confirmar a sua estabilidade, não indicou a existência de interação entre o fármaco e o polímero. O estudo de liberação in vitro indicou que o sistema apresenta perfil de liberação prolongada. O estudo in vivo confirmou o perfil de liberação prolongado do AP a partir das MEs, sugerindo, também, a viabilidade do sistema devido à ausência de toxicidade local. CONCLUSÃO: O conjunto dos resultados obtidos neste trabalho é relevante e credencia o sistema desenvolvido como uma possível alternativa ao tratamento de orbitopatias inflamatórias.
PURPOSE: The present study aimed to evaluate an injectable extended-release formulation of prednisolone acetate (PA) for orbital administration. METHODS: Microspheres (MEs) of poly-e-caprolactone (PCL) containing PA were developed by the method of solvent evaporation. The MEs obtained were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), encapsulation efficiency and in vitro release profile. The in vivo release profile was evaluated in rabbits after periocular injection of an aqueous suspension of MEs. The local biocompatibility of the system was verified by histopathologic analysis of the deployment region. RESULTS: After MEs preparation, morphological analysis by SEM showed the feasibility of the employed method. The content of PA encapsulated was 43 ± 7 percent and can be considered as satisfactory. The system characterization by DSC technique, in addition to confirm the system stability, did not indicate the existence of interaction between the drug and the polymer. The in vitro release study showed the prolonged-release features of the developed system. Preliminary in vivo study showed the absence of local toxicity and confirmed the prolonged release profile of PA from MEs, suggesting the viability of the developed system for the treatment of orbital inflammatory diseases. CONCLUSION: The results obtained in this work are relevant and accredit the system developed as a possible alternative to the treatment of inflammatory orbitopathy.
Assuntos
Animais , Feminino , Coelhos , Anti-Inflamatórios/administração & dosagem , Materiais Biocompatíveis/química , Prednisolona/análogos & derivados , Corpo Vítreo/efeitos dos fármacos , Varredura Diferencial de Calorimetria , Preparações de Ação Retardada/administração & dosagem , Portadores de Fármacos/administração & dosagem , Teste de Materiais , Microscopia Eletrônica de Varredura , Microesferas , Poliésteres/administração & dosagem , Prednisolona/administração & dosagemRESUMO
PURPOSE: To evaluate retinal toxicity of varying doses of rapamycin when injected intravitreally in rabbits. Rapamycin is a potent immunosuppressive agent with significant antitumor and antiangiogenic properties, clinically approved for prevention of organ transplant rejection. METHODS: Twelve New Zealand albino rabbits were divided into four groups. Four different doses of rapamycin were prepared in 0.1 ml: 20 microg, 50 microg, 200 microg, and 1000 microg. Each concentration was injected in one eye of three rabbits, and 0.1 ml volume of sterile BSS was injected into the contralateral eye of the three rabbits. Slit-lamp and fundoscopic examinations were performed and the animals were observed for 2 weeks for signs of infection, inflammation, and toxicity. A baseline ERG was performed before drug treatment and at day 14, after which the rabbits were euthanized. Histology of the enucleated eyes was studied to look for retinal toxicity. RESULTS: ERG results showed some decrease in scotopic response; however this was not dose related. ERG results were normal at 20 microg. Histological results showed no retinal toxicity in all groups. CONCLUSION: Although ERG changes were identified at dosages between 50-1000 microg, the histology of all groups up to 1000 microg did not show any discernable abnormalities.