RESUMO
PURPOSE: To evaluate the feasibility, advantages, and safety of a novel lutein-based dye for improving identification and removal of the vitreous, internal limiting membrane, and epiretinal membrane during chromovitrectomy in humans. METHODS: We prospectively evaluated 12 eyes that underwent pars plana vitrectomy using the dye in patients with macular hole, epiretinal membrane, or proliferative diabetic retinopathy/tractional diabetic macular edema. One surgeon performed standard chromovitrectomy and completed a postoperative questionnaire to compare the staining with that of the available dyes. The peeled membranes were evaluated histologically. Follow-up examinations were performed on postoperative Days 1, 7, 30, 90 and 180; best-corrected visual acuity, optical coherence tomography, fluorescein angiography, autofluorescence, and visual fields were performed. RESULTS: The green dye was deposited on the posterior pole because of its higher density than balanced saline solution; vigorous dye flushing into the vitreous cavity was unnecessary. The dye stained the posterior hyaloid/vitreous base by deposition onto the vitreous; brilliant blue stained the internal limiting membrane. The epiretinal membrane was poorly stained. The best-corrected visual acuity improved in all eyes without clinical toxicity or toxicity on images/visual fields. Histology showed effective removal of the internal limiting membrane and epiretinal membrane in all eyes. CONCLUSION: The new dye improved intraoperative identification of the internal limiting membrane and the posterior hyaloid/vitreous base during chromovitrectomy.
Assuntos
Membrana Basal/patologia , Benzenossulfonatos , Corantes , Luteína , Doenças Retinianas/cirurgia , Vitrectomia , Corpo Vítreo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Membrana Basal/cirurgia , Combinação de Medicamentos , Estudos de Viabilidade , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Óptica , Estudos Prospectivos , Coloração e Rotulagem/métodos , Inquéritos e Questionários , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Corpo Vítreo/cirurgiaRESUMO
INTRODUCTION: Intravitreal injections are a very common procedure and are the most effective route of drug delivery to the retina. There are currently several drugs available and even more are in development; therefore, safety is a very important concern. AREAS COVERED: The toxicological considerations of the most common drugs used for intravitreal pharmacotherapy such as anti-VEGFs, corticosteroids and antibiotics. Emerging agents such as anti-TNFs, VEGF-trap and kinase inhibitors are also discussed. An assessment of the efficacy and safety issues of the most relevant drugs including bevacizumab, ranibizumab and triamcinolone is presented. EXPERT OPINION: The toxicology and safety profiles are available for several drugs that are either in use or will be available for intravitreal injections. Retinal pharmacotherapy is very effective for different retinal diseases; however safety is a very important issue when intravitreal injections are applied and the possibility of retinal toxicity should always be kept in mind. Bevacizumab and ranibizumab are effective for the therapy of wet-age-related macular degeneration and macular edema, while triamcinolone remains an alternative agent to treat secondary macular edema. It is important, as some of these drugs will be used for extended periods of time, that their long-term toxicological effects are better understood.
Assuntos
Anticorpos Monoclonais Humanizados/toxicidade , Injeções Intravítreas/métodos , Triancinolona/toxicidade , Animais , Antibacterianos/uso terapêutico , Bevacizumab , Ensaios Clínicos como Assunto , Humanos , Injeções Intravítreas/efeitos adversos , Degeneração Macular/tratamento farmacológico , Edema Macular/tratamento farmacológico , Ranibizumab , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
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.
Assuntos
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
Diabetic macular edema (DME) is the most frequent cause of severe vision impairment in patients with non-proliferative diabetic retinopathy. Even though patients should achieve optimal glycemic control, normalization of blood pressure and serum lipids, as well as improvement of cardiac and renal status, these measures alone will not prevent every patient from developing visual loss caused by DME. The goal of local treatment for DME is vision improvement, usually achieved after reducing leakage on fluorescein angiography (FA) and retinal thickness on optical coherence tomography (OCT). Laser photocoagulation is still the standard treatment for clinically significant DME. However, laser photocoagulation rarely provides major visual improvement, especially in patients with diffuse DME. Thus, a therapeutic intervention that restores visual acuity impaired by DME more often remains a significant unmet medical need. This review aims to present the most important emerging drug technologies for therapy of DME at present, including corticosteroids, vascular endothelial growth factor inhibitors, protein kinase C inhibitors, small interfering RNA, hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors and non-hormonal anti-inflammatory agents. Recent progress in this field suggests that local management of DME may change rapidly in the near future. Novel emerging drugs should enable better anatomical and functional outcomes for therapy of this sight-threatening disease.