Letter to the Editor
Ocular surface toxicity associated with epidermal growth factor receptor inhibitors
Toxicidad de la superficie ocular asociada a inhibidores del receptor del factor de crecimiento epidérmico
Borja Arias-Peso
, Álvaro Tello Fernández, Mohamed Bakkali el Bakkali
Corresponding author
Servicio de Oftalmología, Hospital Universitario Miguel Servet, Zaragoza, Spain
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(a) Blepharoconjunctivitis in patient treated with cetuximab; (b) trichomegaly (identified by arrow) in patient treated with cetuximab; (c) trichomegaly (identified by arrow) in patient treated with cetuximab; (d) trichomegaly, poliosis (identified by arrow); (e) corneal erosion (identified by asterisk*) in patient treated with cetuximab; (f) blepharoconjunctivitis in patient treated with panitumumab.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In the era of personalised medicine, targeted cancer therapy has revolutionised the treatment of different malignancies. Its higher specificity and lower systemic toxicity are its main advantages compared to conventional chemotherapy. However, the eye is an organ that is particularly susceptible to the effects of these drugs due to the abundant distribution of specific receptors.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The epidermal growth factor receptor (EGFR) inhibitors of are one of the most developed groups. These include the monoclonal antibodies cetuximab and panitumumab, used in the treatment of colorectal and head and neck cancer. Although skin reactions are the most common adverse reaction, ocular toxicity has also been described to a lesser extent.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The present work aims to show the spectrum of ocular toxicity associated with these drugs.</p><p id="par0015" class="elsevierStylePara elsevierViewall">We report a case series of ocular toxicity in patients treated with EGFR inhibitors who were referred to the Ophthalmology Department of a tertiary hospital.</p><p id="par0020" class="elsevierStylePara elsevierViewall">A total of 6 patients (2 women) were identified with a mean age of 63 years (range 52–74) at the time of diagnosis. All patients were being treated with a monoclonal antibody directed against EGFR (cetuximab in 5 cases and panitumumab in 1). The main indication for treatment was metastatic colorectal carcinoma in all cases except one, which was basaloid squamous cell carcinoma of the head and neck.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Regarding the type of ocular toxicity, blepharoconjunctivitis was diagnosed in two cases, trichomegaly in three (together with grey hair in one of them) and corneal epitheliopathy in one case (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The cases of blepharoconjunctivitis showed scaly lesions with associated eyelid erythema. In the trichomegaly cases, an excessive growth of the eyelashes was observed, associating poliosis in one of the cases. None of the trichomegaly cases associated signs of secondary corneal involvement. In the case of corneal epitheliopathy, a central epithelial defect was shown with involvement of the pupillary axis.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Patients diagnosed with blepharoconjunctivitis received topical antibiotic and corticosteroid treatment along with general recommendations for eyelid hygiene. Since trichomegaly cases did not associate corneal erosions, only prophylactic treatment with ocular lubrication was necessary. In the case of corneal epitheliopathy, the use of a topical antibiotic associated with a night-time lubricating ointment was used. A subsequent follow-up was carried out with good progression and optimal response to the prescribed topical treatment, not being necessary to discontinue or change the drug.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The most common and best-known adverse reaction of EGFRs is their skin toxicity in the form of an acneiform rash, which affects more than 80% of patients. In contrast to this known adverse reaction, information on ocular toxicity is limited and there are few published cases to date.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The spectrum of ocular toxicity associated with EGFR inhibition is very broad, with dry eye being the most common disorder followed by blepharitis and trichomegaly.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2–4</span></a> The mechanism by which EGFR inhibition causes damage to ocular structures is not fully understood. In the case of blepharitis, a blockade of the EGFR expressed in the Meibomian glands has been suggested to occur in the same way as in the sweat glands. This blockade of the Meibomian glands would cause a secretory dysfunction leading to alterations of the free edge of the eyelashes.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> In the case series presented, one of the patients with blepharitis simultaneously associated skin toxicity, which would support a common pathogenesis. A similar effect would occur in cases of trichomegaly, as well as in corneal epitheliopathy, where epidermal growth factor plays a key role in the proliferation of epithelial cells.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Although ocular toxicity associated with these drugs is not serious, it can significantly affect the visual function and the quality of life of these patients. Collaborative work between oncologists and ophthalmologists is essential in the management of complications secondary to the new targeted cancer therapy. The reporting of new cases is important in order to better understand the pathogenesis and thus optimise treatment.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Arias-Peso B, Tello Fernández Á, Bakkali el Bakkali M. Toxicidad de la superficie ocular asociada a inhibidores del receptor del factor de crecimiento epidérmico. Med Clin (Barc). 2021;157:401–402.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 759 "Ancho" => 1750 "Tamanyo" => 186360 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Images of ocular toxicity in the patient series. (a) Blepharoconjunctivitis in patient treated with cetuximab; (b) trichomegaly (identified by arrow) in patient treated with cetuximab; (c) trichomegaly (identified by arrow) in patient treated with cetuximab; (d) trichomegaly, poliosis (identified by arrow); (e) corneal erosion (identified by asterisk*) in patient treated with cetuximab; (f) blepharoconjunctivitis in patient treated with panitumumab.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ocular toxicity of targeted therapies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "D.J. Renouf" 1 => "J.P. Velazquez-Martin" 2 => "R. Simpson" 3 => "L.L. Siu" 4 => "P.L. 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