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    Retinal and Ocular Toxicity in Ocular Application of Drugs and Chemicals - Part II: Retinal Toxicity of Current and New Drugs
    (Karger, 2010-01-01) Penha, Fernando Marcondes [UNIFESP]; Rodrigues, Eduardo Buchele [UNIFESP]; Maia, Mauricio [UNIFESP]; Furlani, Bruno de Alburquerque [UNIFESP]; Regatieri, Caio Vinicius Saito [UNIFESP]; Melo, Gustavo Barreto de [UNIFESP]; Magalhães, Octaviano [UNIFESP]; Manzano, Roberta [UNIFESP]; Farah, Michel Eid [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    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. Copyright (C) 2010 S. Karger AG, Basel
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    Therapeutic monoclonal antibodies in ophthalmology
    (Elsevier B.V., 2009-03-01) Rodrigues, Eduardo B. [UNIFESP]; Farah, Michel E. [UNIFESP]; Maia, Mauricio [UNIFESP]; Penha, Fernando M. [UNIFESP]; Regatieri, Caio [UNIFESP]; Melo, Gustavo B. [UNIFESP]; Pinheiro, Marcelo M. [UNIFESP]; Zanetti, Carlos R.; Universidade Federal de São Paulo (UNIFESP); Universidade Federal de Santa Catarina (UFSC)
    Monoclonal antibodies (mAbs) can be used therapeutically by binding to molecular targets with high specificity. Therefore, they have excellent therapeutic applications in ophthalmology. This manuscript presents four aspects of the therapeutic use of mAbs in ophthalmology: the scientific rationale, the unique characteristics of selected mAbs, the current state-of-the-art application, and relevant therapeutic mAbs for future applications in ophthalmology. We identified in the literature various single-agent therapies that inhibit the following targets: tumor necrosis factor (TNF), epithelial growth factor receptor, vascular endothelial growth factor (VEGF) receptor, basic fibroblast growth factor receptor, platelet-derived growth factor, and cluster of differentiation antigens. the roles of all biochemical targets in ocular diseases were evaluated. Current and future mAbs against various cytokines were assessed for the treatment of ocular diseases. the medical literature showed the clinical benefits of mAbs for treating angiogenic and inflammatory ocular diseases. Two anti-VEGF mAbs, bevacizumab and ranibizumab, and three anti-TNF agents, infliximab, etanercept, and adalimumab, control Ocular neovascularization and intraocular inflammation. Other mAbs such as rituximab, daclizumab, efalizumab, and alemtuzumab showed positive results in animal and early clinical studies and may represent useful adjuvant therapies for ocular lymphoma or ocular inflammation. Ranibizumab is the only FDA-approved therapy; for other mAbs the so-called off-label application remains the standard. Intravenous administration of mAbs has demonstrated acceptable toxicity profiles, while intraocular injection may decrease the chances of systemic complications and increase the amount of drug available to the retina and choroid. in conclusion, effective clinical use of mAbs in ophthalmology is more commonly seen in the field of angiogenic vitreoretinal and autoimmune inflammatory diseases. the challenge for the future is combining biologic therapies to improve the quality and duration of responses while diminishing side effects. the role of mAbs within ophthalmic treatments will be defined according to future clinical experience and the results of randomized clinical trials. (C) 2008 Elsevier B.V. All rights reserved.