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Topical insulin in neurotrophic keratopathy after resection of acoustic neuroma
Insulina tópica en queratopatía neurotrófica tras resección de neurinoma del acústico
V. Galvisa,c, C.A. Niñoa,b, A. Telloa,c,
Corresponding author
alejandrotello@gmail.com

Corresponding author.
, J.M. Gricea, M.A. Gómeza
a Centro Oftalmológico Virgilio Galvis, Floridablanca, Santander, Colombia
b Departamento de Oftalmología, Fundación Oftalmológica de Santander FOSCAL, Floridablanca, Santander, Colombia
c Departamento de Oftalmología, Facultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga, Bucaramanga, Santander, Colombia
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who also presented infectious keratitis&#46; Finally&#44; corneal epithelial closure was achieved with the use of topical insulin&#44; recently described as co-adjuvant in the management of corneal ulcers&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3&#44;4</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Clinical case report</span><p id="par0010" class="elsevierStylePara elsevierViewall">A 48 years-old woman with history of neurinoma resection of the left acoustic nerve&#44; who consulted 5 days after surgery with blurred vision and tearing in the left eye &#40;LE&#41;&#46; The patient was receiving artificial tears&#46; Corrected visual acuity was 20&#47;20 in the right eye &#40;RE&#41; and 20&#47;80 in LE&#46; The LE exhibited lagophthalmos and severe superficial punctate keratitis&#46; Left peripheral facial paralysis was diagnosed&#46; Treatment was continued with 0&#46;4&#37; preservative-free sodium hyaluronate&#44; indicating palpebral occlusion during the night&#46; At the time&#44; trigeminal nerve compromise was not diagnosed&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Two weeks later&#44; the patient consulted indicating that she had to visit the Emergency Dept&#46; due to conjunctival injection and vision worsening&#46; She had been prescribed 0&#46;5&#37; topical moxifloxacin&#46; Examination showed temporal paracentral ulcer measuring approximately 1<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>mm&#44; compromising anterior stroma&#44; and &#43;cellularity in LE anterior chamber&#46; Lubricant was continued and treatment with bi-conjugated 0&#46;5&#37; moxifloxacin and 0&#46;1&#37; dexamethasone eyedrops was prescribed in order to add topical steroids &#40;as suggested by Steroids for Corneal Ulcer Trials&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> Evolution was torpid&#44; for which reason corneal scraping was conducted 2 days later for microbiological studies&#44; and topical 3&#46;1&#37; vancomycin every hour was added&#46; Culture was positive for <span class="elsevierStyleItalic">Staphylococcus aureus</span>&#44; sensitive to moxifloxacin and vancomycin&#46; Four days later&#44; the infectious condition exhibited signs of improvement with diminished corneal infiltrate density&#46; However&#44; the epithelial defect measuring approximately 6&#46;2<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>5&#46;4<span class="elsevierStyleHsp" style=""></span>mm persisted&#46; The measurement was taken utilizing the ImageJ application &#40;version 1&#46;52a&#59; National Institutes of Health&#41; taking as reference the corneal diameter determined with IOLMaster<span class="elsevierStyleSup">&#174;</span> 700&#44; which was 11&#46;3<span class="elsevierStyleHsp" style=""></span>mm &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>a&#41;&#46; Oral ascorbic acid &#40;3<span class="elsevierStyleHsp" style=""></span>g&#47;day&#41; and doxycycline &#40;100<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; were added&#46; Two days later a defect of approximately 7&#46;4<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>6&#46;8<span class="elsevierStyleHsp" style=""></span>mm &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>b&#41; was observed&#44; at which time autologous plasma enriched with platelet growth factor was added&#46; Three days later&#44; the de-epithelized area was larger&#44; measuring 7&#46;6<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>7&#46;6<span class="elsevierStyleHsp" style=""></span>mm &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>c&#41;&#46; A re-evaluation of the case found that&#44; since before surgery&#44; the patient exhibited left hemifacial hypoesthesia&#44; and examination confirmed the presence of corneal hypoesthesia&#44; which led to the diagnostic of neurotrophic ulcer with concomitant compromise of the trigeminal and facial nerves&#46; Topical steroids were suspended&#44; and topical antibiotics were maintained and a therapeutic contact lens was placed&#46; However&#44; 3 days later even though the de-epithelized area had slightly diminished &#40;5&#46;7<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>5&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#41;&#44; it was decided to remove the contact lens due to the finding of greater conjunctival injection and mucopurulent secretion as well as increased stromal corneal infiltrate density together with some folds in Descemet membrane&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The possibility of amniotic membrane graft was considered &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>d&#41;&#46; One week after initiating autologous plasma treatment the epithelial defect persisted&#44; measuring approximately 6&#46;4<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>6&#46;2<span class="elsevierStyleHsp" style=""></span>mm &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>a&#41;&#46; A last option prior to surgery consisted in adding topical insulin &#40;1<span class="elsevierStyleHsp" style=""></span>UI&#47;ml&#41; to the treatment&#44; prepared diluting human insulin in polyethylene glycol 400&#47;propylene glycol &#40;Humulin<span class="elsevierStyleSup">&#174;</span> N &#91;Lilly Laboratories&#44; Indianapolis&#44; IN&#44; United States&#93; diluted in Systane Ultra<span class="elsevierStyleSup">&#174;</span> &#91;Alcon&#44; Fort Worth&#44; TX&#44; United States&#93;&#41;&#44; applied one drop 4 times a day&#46; Vancomycin was suspended&#46; Five days after initiating insulin treatment&#44; a clear regression of the defect was observed&#44; measuring 2&#46;4<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>2&#46;9<span class="elsevierStyleHsp" style=""></span>mm &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>b&#41; and accordingly the amniotic membrane transplant was canceled&#46; Tropicamide was added due to the presence of posterior synechia&#46; Four days later a slightly larger lesion persisted &#40;approximately 3&#46;1<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>3&#46;4<span class="elsevierStyleHsp" style=""></span>mm&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>c&#41; and a therapeutic contact lens was placed again&#46; Finally&#44; after completing 14 days of insulin treatment&#44; complete corneal epithelization was observed with epithelial irregularities that minimally stained with fluorescein &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>d&#41;&#46; Subsequently&#44; the contact lens was removed and the patient was recommended to continue occlusion with microporous adhesive tape&#46; In the last checkup visit&#44; 4 months after the onset of the condition&#44; low density temporal paracentral leukoma without staining was observed &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>a&#8211;c&#41;&#46; Corrected visual acuity reached 20&#47;40 in LE&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Discussion</span><p id="par0025" class="elsevierStylePara elsevierViewall">In 1945&#44; Ainsley reported the use of insulin in 5 patients with corneal ulcers&#44; one with topical treatment and 4 with injections&#44; obtaining good results&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Surprisingly&#44; during nearly 5 decades this option was never mentioned in ophthalmological literature&#46; In 1994&#44; a study exploring the ocular topical route as alternative to subcutaneous application of insulin in diabetics was published&#44; demonstrating that insulin in saline solution was not toxic for the human eye after multiple applications during 8 weeks&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> The case of a child with a form of Riley-Day syndrome was reported in 1997&#46; The child did not respond to 10 days topical insulin treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> An <span class="elsevierStyleItalic">in vitro</span> experiment published in 2004 reported that insulin increased re-epithelization of small wounds created in monolayers of cultured human corneal epithelial cells&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In 2007&#44; an experimental study demonstrated that topical treatment with insulin for corneal abrasions in diabetic rats avoided delayed epithelial wound healing that was observed in poorly controlled diabetic animals&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> In 2013&#44; a study by Bastion and Ling demonstrated that topical insulin facilitated the normalization of cicatrization of defects in diabetic patients who underwent epithelial debridement to improve surgeon vision during posterior vitrectomy&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In 2017&#44; Wang et al&#46; published a 6-case series of neurotrophic keratopathy treated with topical insulin&#46; To date&#44; this is the only published series reporting ulcers with said etiology&#46; All patients exhibited healing of the cornea between 7 and 25 days&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> In the present case&#44; the patient exhibited a combination of exposure keratopathy secondary to peripheral facial nerve palsy and neurotrophic keratopathy due to left trigeminal nerve alteration associated to the history of surgery for left acoustic neurinoma&#46; In a recently published series comprising 174 patients who underwent surgical resection of this type of tumor&#44; only 4 cases &#40;2&#46;3&#37;&#41; exhibited the sequel of simultaneous compromise of said 2 nerves&#46; However&#44; taking into account that the mean size of tumors in these 4 patients was 4<span class="elsevierStyleHsp" style=""></span>cm&#44; the possibility that tumor resection of said size or larger could affect both nerves is high&#44; because only 19 cases reached said size&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Another series that comprised 54 patients with tumors measuring 2&#46;5<span class="elsevierStyleHsp" style=""></span>cm or more&#44; 30&#37; exhibited preoperative corneal innervation compromise while 48&#37; exhibited this compromise after surgical resection of the tumor&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> In addition to exhibiting compromise of both cranial nerves&#44; the present case had corneal infection which further delayed the recovery&#46; She did not respond to autologous plasma&#44; and epithelization was finally achieved with the use of topical insulin and a therapeutic contact lens&#46; Even though the addition of insulin had an obvious positive effect&#44; it is not possible to state with certainty that the ulcer would have closed without the new application of said contact lens&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The use of steroids in bacterial corneal ulcers has been controversial for many years&#46; The subgroup analysis of the <span class="elsevierStyleItalic">Steroids for Corneal Ulcer Trials</span> suggested that topical steroids could be beneficial after early administration for central corneal ulcers&#46; Said finding led to the topical steroid treatment in this case&#44; although it did not evidence positive results&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In what concerns the use of topical insulin in corneal ulcers&#44; in order to take an evidence-based decision prospective studies with control groups would be required in order to confirm the beneficial effect thereof&#46; However&#44; in uncommon diseases it is not easy to conduct clinic trials&#46; On the other hand&#44; the absence of toxicity and the benefits reported in the few published cases&#44; including the present one&#44; has been notorious &#40;with a single exception&#41;&#46; Accordingly&#44; the authors believe that the use of topical insulin to promote cicatrization in neurotrophic corneal ulcers is justified and can be combined with other treatment options such as therapeutic contact lens&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3&#44;4&#44;6&#44;10</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conflict of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">No conflict of interest was declared by the authors&#46;</p></span></span>"
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            0 => "Keratitis"
            1 => "Corneal ulcer"
            2 => "Insulin"
            3 => "Schwannoma"
            4 => "Facial nerve"
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            0 => "Queratitis"
            1 => "&#218;lcera de la c&#243;rnea"
            2 => "Insulina"
            3 => "Schwannoma"
            4 => "Nervio facial"
            5 => "Nervio trig&#233;mino"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Case report</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A patient with a history of surgical resection of an acoustic neuroma presented with involvement of both the left facial nerve and the left trigeminal nerve&#46; She initially consulted for exposure keratitis&#44; but two weeks later presented with an infectious keratitis&#46; After taking the corneal sample&#44; she presented with persistent epithelial defect&#44; which did not respond to medical management&#46; Topical insulin was indicated&#44; and a decrease in the area of the lesion was seen in the following 5 days&#46; A therapeutic contact lens was also placed at that time and finally&#44; two weeks after the initiation of insulin&#44; the epithelial defect completely closed&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Discussion</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This was a complex case due to the confluence of facial paralysis&#44; neurotrophic keratitis&#44; and infectious keratitis&#44; which finally had a successful outcome&#46; Topical insulin can be an effective adjuvant therapy in cases of neurotrophic ulcers that do not respond to standard therapy&#46;</p></span>"
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        "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Caso cl&#237;nico</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Una paciente con antecedente de resecci&#243;n quir&#250;rgica de un neurinoma del ac&#250;stico present&#243; compromiso tanto del nervio facial como del nervio trig&#233;mino izquierdos&#46; Inicialmente consult&#243; por queratitis de exposici&#243;n&#44; pero 2 semanas despu&#233;s present&#243; una queratitis infecciosa&#46; Tras la toma de la muestra corneal curs&#243; con un defecto epitelial persistente&#44; que no respondi&#243; al manejo m&#233;dico&#46; Se indic&#243; insulina t&#243;pica con lo que se evidenci&#243; disminuci&#243;n del &#225;rea de la lesi&#243;n en los siguientes 5 d&#237;as&#46; Se coloc&#243; adem&#225;s&#44; en ese momento&#44; una lente de contacto terap&#233;utica y&#44; finalmente&#44; 2 semanas despu&#233;s de haberse iniciado la insulina&#44; el defecto epitelial cerr&#243; por completo&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Discusi&#243;n</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Se trata de un caso complejo por la confluencia de par&#225;lisis facial&#44; queratitis neurotr&#243;fica y queratitis infecciosa&#44; que finalmente tuvo un resultado exitoso&#46; La insulina t&#243;pica puede ser una terapia coadyuvante efectiva en casos de &#250;lceras neurotr&#243;ficas que no respondan a la terapia convencional&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Galvis V&#44; Ni&#241;o CA&#44; Tello A&#44; Grice JM&#44; G&#243;mez MA&#46; Insulina t&#243;pica en queratopat&#237;a neurotr&#243;fica tras resecci&#243;n de neurinoma del ac&#250;stico&#46; Arch Soc Esp Oftalmol&#46; 2019&#59;94&#58;100&#8211;104&#46;</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; Four days after taking the microbiological sample&#44; the size of the epithelial defect secondary to diagnostic debridement had increased to 6&#46;2<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>5&#46;4<span class="elsevierStyleHsp" style=""></span>mm&#44; measured with the ImageJ application &#40;version 1&#46;52a&#59; <span class="elsevierStyleItalic">National Institutes of Health</span>&#41; taking as reference the corneal diameter measured with IOL Master<span class="elsevierStyleSup">&#174;</span> 700&#44; that was 11&#46;3<span class="elsevierStyleHsp" style=""></span>mm&#59; &#40;b&#41; two and &#40;c&#41; five days later&#44; the epithelial defect size was even larger&#58; 7&#46;4<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>6&#46;8<span class="elsevierStyleHsp" style=""></span>mm and 7&#46;6<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>7&#46;6<span class="elsevierStyleHsp" style=""></span>mm on the other hand&#44; the inflammatory infiltrate density related to infectious keratitis had diminished &#40;white arrows&#41;&#59; &#40;d&#41; three days after initiating autologous plasma and placing a therapeutic contact lens&#44; even though the size of the epithelial defect was smaller &#40;5&#46;7<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>5&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#41;&#44; the conjunctival injection worsened&#44; exhibiting conjunctival secretion and corneal edema&#44; and the density of the infiltrate area seemed to worsen &#40;red arrow&#41;&#44; for which reason the contact lens was removed&#46;</p>"
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; Persistence of epithelial defect maintaining similar size &#40;6&#46;4<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>6&#46;2<span class="elsevierStyleHsp" style=""></span>mm&#41; one week after initiating autologous plasma treatment&#59; &#40;b&#41; five days after adding topical insulin&#44; the de-epithelized area size diminished significantly &#40;2&#46;4<span class="elsevierStyleHsp" style=""></span>mm in the largest horizontal diameter<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>2&#46;9<span class="elsevierStyleHsp" style=""></span>mm vertical&#41;&#59; &#40;c&#41; three days later a somewhat larger defect persisted &#40;3&#46;1<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>3&#46;4<span class="elsevierStyleHsp" style=""></span>mm&#41; for which reason the therapeutic contact lens was utilized again&#59; &#40;d&#41; two weeks after initiating topical insulin treatment&#44; the complete epithelization of the defect was finally achieved&#46;</p>"
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; In the last checkup&#44; complete corneal epithelization could be observed&#59; &#40;b&#41; leukoma density in the infectious infiltrate area diminished notoriously &#40;white arrow&#41;&#59; &#40;c&#41; no fluorescein staining&#46;</p>"
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      "seccion" => array:1 [
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              "etiqueta" => "1"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Trigeminal nerve deficit in large and compressive acoustic neuromas and its correlation with MRI findings"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46; Karkas"
                            1 => "E&#46; Lamblin"
                            2 => "M&#46; Meyer"
                            3 => "E&#46; Gay"
                            4 => "J&#46; Ternier"
                            5 => "S&#46; Schmerber"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/0194599814545440"
                      "Revista" => array:6 [
                        "tituloSerie" => "Otolaryngol Head Neck Surg"
                        "fecha" => "2014"
                        "volumen" => "151"
                        "paginaInicial" => "675"
                        "paginaFinal" => "680"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25085321"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ophthalmic complications following acoustic neuroma resection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

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Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos