Intravitreal bevacizumab: Is it exempt from adverse extraocular effects?

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"tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "225" "paginaFinal" => "226" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "M. Sánchez López, M.A. Navarro Puerto, I. Gutiérrez Morales" "autores" => array:3 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "Sánchez López" "email" => array:1 [ 0 => "marinasanlop@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M.A." "apellidos" => "Navarro Puerto" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "I." "apellidos" => "Gutiérrez Morales" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Medicina Familiar y Comunitaria, Hospital Universitario de Valme, Sevilla, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Gestión Clínica de Medicina Interna, Hospital Universitario de Valme, Sevilla, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Unidad de Gestión Clínica de Cuidados Críticos y Urgencias, Hospital Universitario de Valme, Sevilla, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Bevacizumab intravítreo, ¿está exento de efectos adversos extraoculares?" ] ] "textoCompleto" => "Bevacizumab is an antineoplastic drug that acts as a monoclonal antibody and binds to vascular endothelial growth factor (VEGF), a key component of vasculogenesis and angiogenesis, thereby inhibiting the binding of this factor to its receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2), located on the surface of endothelial cells. The neutralization of VEGF's biological activity produces a regression in tumor vascularization, inhibits tumor neovascularization and thereby inhibits tumor growth (breast, colon, non-small cell lung, kidney, ovarian, etc.).The use of bevacizumab has extended to other diseases with vascular proliferation, such as ocular disease (through intravitreal administration) and age-related macular degeneration, proliferative diabetic retinopathy, macular edema, retinopathy of prematurity<a class="elsevierStyleCrossRef" href="#bib0025">1</a> and even in individual cases of ocular melanoma.<a class="elsevierStyleCrossRef" href="#bib0030">2</a>The intravitreal use of bevacizumab is not approved according to its datasheet, because the compound has not been developed for this administration route.The most common adverse effects of bevacizumab when administered parenterally as an antineoplastic agent are similar to those observed with chemotherapy and can exacerbate them when combined with these chemotherapy agents. The most common adverse reactions include pancytopenia, anorexia, hyponatremia, peripheral sensory neuropathy, dysgeusia, ocular disorder, arterial hypertension, thromboembolism, rhinitis, dyspnea, diarrhea, nausea, vomiting, dermatitis, joint pain, myalgia, asthenia, mucositis and weight loss.<a class="elsevierStyleCrossRef" href="#bib0025">1</a>Individual cases and severe ocular adverse reactions have been reported after its intravitreal use, such as infectious endophthalmitis, intraocular inflammation (sterile endophthalmitis, uveitis, vitritis), retinal detachment, lacerations of the epithelial retinal pigments, increased intraocular pressure and intraocular hemorrhage (vitreous, retinal, conjunctival). Some of these reactions have caused vision loss to varying degrees, including permanent blindness.<a class="elsevierStyleCrossRef" href="#bib0035">3</a>After an intravitreal anti-VEGF treatment, reductions have been shown in the circulating VEGF concentration.<a class="elsevierStyleCrossRef" href="#bib0040">4</a> Nevertheless, systemic adverse reactions have been reported after the administration of VEGF, such as nonocular hemorrhaging and thromboembolism.<a class="elsevierStyleCrossRef" href="#bib0035">3</a>A recent study compared the pharmacokinetics of 3 monoclonal anti-VEGF antibodies after their intravitreal administration. Bevacizumab achieved the highest systemic concentrations compared with aflibercept and ranibizumab and therefore presented the largest number of adverse reactions.<a class="elsevierStyleCrossRef" href="#bib0040">4</a>We present a case in which we show the unusual potential adverse effects from the intravitreal administration of bevacizumab, effects not present in the consulted literature.The case involves a 77-year-old woman who was admitted to internal medicine for dyspnea. The patient's history included arterial hypertension, type 2 diabetes mellitus, paroxysmal atrial fibrillation and bilateral age-associated macular degeneration, treated with intravitreal bevacizumab 10 months earlier. Follow-up was conducted in internal medicine consultations due to anosmia and ageusia, without determining the cause. The patient was examined by the otorhinolaryngology department, who performed fibroscopy and computed tomography of the nasal fossae, with no pathological findings. Treatment was performed with acenocoumarol, furosemide, insulin, omeprazole, carvedilol and amlodipine.During the hospitalization in internal medicine and once the dyspnea and pneumonia had improved, the predominant symptoms were anosmia and ageusia, showing constitutional symptoms of anorexia secondary to the predominant symptoms.Faced with a ground-glass pattern in the computed tomography and mediastinal adenopathies, we conducted a broad study (tumor markers, fibrobronchoscopy and bronchoalveolar lavage, proteinogram, angiotensin-converting enzyme, serology) to rule out a solid neoplasm, a lymphoproliferative process, disease infiltration and sarcoidosis, the results of all of which were negative. After starting empiric treatment with corticosteroids, the adenopathies decreased in size considerably, the patient improved clinically, and the dyspnea ceased. Given this result and the patient's wishes, no further studies were performed.Due to persistent anosmia and ageusia, we conducted a review of the potential etiologies and management of these symptoms. We started treatment with clonazepam, with slight improvement but with an early withdrawal due to intolerance to clonazepam.Therefore, this case involves a patient with anosmia and ageusia secondary to the intravitreal administration of bevacizumab. We reached this conclusion after a broad study that resulted in no findings related to these symptoms and no other history that would explain them. There was also a clear temporal cause-and-effect relationship after the administration of bevacizumab and the development of symptoms.With the publication of this case, we wish to note the importance of keeping in mind the uncommon potential adverse effects, not described in the literature, related to the intravitreal administration of bevacizumab and assess the risk-benefit in terms of its administration and inform patients of the potential complications." "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Sánchez López M, Navarro Puerto MA, Gutiérrez Morales I. Bevacizumab intravítreo, ¿está exento de efectos adversos extraoculares? Rev Clin Esp. 2019;219:225–226." ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:4 [ 0 => array:3 [ "identificador" => "bib0025" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Ficha técnica bevacizumab. Available from: <a id="intr0010" class="elsevierStyleInterRef" href="https://ec.europa.eu/health/documents/community-register/2012/20120830124164/anx_124164_es.pdf">https://ec.europa.eu/health/documents/community-register/2012/20120830124164/anx_124164_es.pdf</a> [accessed 08.02.18]." ] ] ] 1 => array:3 [ "identificador" => "bib0030" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Growth of uveal melanoma following intravitreal bevacizumab" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J.H. Francis" 1 => "J. Kim" 2 => "A. Lin" 3 => "R. Folberg" 4 => "S. Iyer" 5 => "D.H. Abramson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000450859" "Revista" => array:6 [ "tituloSerie" => "Ocul Oncol Pathol" "fecha" => "2017" "volumen" => "3" "paginaInicial" => "117" "paginaFinal" => "121" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28868282" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0035" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Complications in patients after intravitreal injection of bevacizumab" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Shima" 1 => "H. Sakaguchi" 2 => "F. Gomi" 3 => "M. Kamei" 4 => "Y. Ikuno" 5 => "Y. 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