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Sales-Sanz, E. Fuentemilla, H.R. Won-Kim, F. de-Arriba-Palomero, F.J. Muñoz-Negrete" "autores" => array:6 [ 0 => array:2 [ "nombre" => "P." "apellidos" => "de-Arriba-Palomero" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Sales-Sanz" ] 2 => array:2 [ "nombre" => "E." "apellidos" => "Fuentemilla" ] 3 => array:2 [ "nombre" => "H.R." "apellidos" => "Won-Kim" ] 4 => array:2 [ "nombre" => "F." "apellidos" => "de-Arriba-Palomero" ] 5 => array:2 [ "nombre" => "F.J." "apellidos" => "Muñoz-Negrete" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0365669119300899" "doi" => "10.1016/j.oftal.2019.03.008" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365669119300899?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579419300751?idApp=UINPBA00004N" "url" => "/21735794/0000009400000007/v1_201907010945/S2173579419300751/v1_201907010945/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S217357941930091X" "issn" => "21735794" "doi" => "10.1016/j.oftale.2019.04.002" "estado" => "S300" "fechaPublicacion" => "2019-07-01" "aid" => "1502" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Arch Soc Esp Oftalmol. 2019;94:313-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1 "HTML" => 1 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Artificial intelligence, robotics and cyborgs: The future of research and technological development in ophthalmology" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "313" "paginaFinal" => "315" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La inteligencia artificial, la robótica y los <span class="elsevierStyleItalic">cíborgs</span>: futuro de la investigación y del desarrollo tecnológico en oftalmología" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J.Á. 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"apellidos" => "Kudsieh" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0365669119301182" "doi" => "10.1016/j.oftal.2019.04.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365669119301182?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S217357941930091X?idApp=UINPBA00004N" "url" => "/21735794/0000009400000007/v1_201907010945/S217357941930091X/v1_201907010945/en/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "Ocular demodicosis: A review" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "316" "paginaFinal" => "322" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "V. Moris García, G. Valenzuela Vargas, M. Marín Cornuy, P. Aguila Torres" "autores" => array:4 [ 0 => array:2 [ "nombre" => "V." "apellidos" => "Moris García" ] 1 => array:2 [ "nombre" => "G." "apellidos" => "Valenzuela Vargas" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Marín Cornuy" ] 3 => array:4 [ "nombre" => "P." "apellidos" => "Aguila Torres" "email" => array:1 [ 0 => "patricia.aguila@uach.cl" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Laboratorio de Microbiología Molecular, Escuela de Tecnología Médica, Universidad Austral de Chile, Puerto Montt, Chile" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Demodicosis ocular: una revisión" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 539 "Ancho" => 805 "Tamanyo" => 50320 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Demodex</span> spp. stained with lactophenol solution. Visualization with light microscope (40×).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Demodex</span> was discovered by Henle in 1841 and classified as a mite by Simón in 1842 (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). From the taxonomic viewpoint, Demodex is grouped as Arthropoda/Chelicerata/Arachnida/Acarina/Demodicidae/Demodex.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">1</span></a> Simón in 1842 and Akbulatova in 1963 were the first to describe <span class="elsevierStyleItalic">Demodex folliculorum</span> and <span class="elsevierStyleItalic">Demodex brevis</span>, respectively. Over 100 species of these mites have been identified, only 2 of which have been found on the skin of humans.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">2</span></a> Both <span class="elsevierStyleItalic">Demodex</span> species have the form of a worm and a thin cuticle. <span class="elsevierStyleItalic">D. folliculorum</span> is 0.3–0.4<span class="elsevierStyleHsp" style=""></span>mm long, while <span class="elsevierStyleItalic">D. brevis</span> measures 0.15–0.2<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleSup">3</span>. They have been found in various areas of the skin, mainly the face, forehead, nose, lips, cheeks, chin and to a lesser extent the head, neck and external auditive duct.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">3</span></a> These organisms reproduce sexually and their lifecycle is approximately 14 days.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">4</span></a> The transmission mechanism is through direct contact of skin with the mite in the larval or adult stage, as well as contact with towels, sheets and dust containing the mite in the oval stage.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">5</span></a> Transmission of mites between individuals does not necessarily produce the disease although it could occur more frequently in immunologically compromised individuals.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">6</span></a> The disease caused by both parasites is known as demodicosis.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">The pathogenic role of <span class="elsevierStyleItalic">Demodex</span> spp. in ophthalmology has been cause of debate for many years due to antecedents of ophthalmological diseases involving significant amount of these mites on the ocular surface such as ocular rosacea, in which it is believed they could cause complications such as superficial corneal neovascularization, marginal corneal infiltration, superficial corneal opacity and nodular corneal scars<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">7</span></a> in addition to other clinic expressions. As <span class="elsevierStyleItalic">Demodex</span> obtain their nutrition from follicular and glandular epithelial cell sebum, they could induce inflammation of the skin or eyelid edges. <span class="elsevierStyleItalic">D. folliculorum</span> resides in hair follicles and <span class="elsevierStyleItalic">D. brevis</span> is found in the sebaceous and Meibomium glands. Both species exhibit a preference for said areas because they feed on the epidermal cells, hormones and fair follicle oils.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">8</span></a> Predisposing factors for infestation by <span class="elsevierStyleItalic">Demodex</span> spp. have been broadly describes and discussed, including age, poor ocular hygiene, use of spectacles, exposure to sunlight, stress, rosaceae, diabetes mellitus, immune deficiency as well as patients being treated for renal insufficiency and leukemia, among others.<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">5,9,10</span></a> Clinic expressions are directly related to the grade of infestation: a density of 5 mites per hair follicle could be interpreted as a considerable infestation.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">11</span></a> However, some authors suggest that <span class="elsevierStyleItalic">Demodex</span> spp. could be beneficial for humans. In 2018, Mastrota pointed out that <span class="elsevierStyleItalic">Demodex</span> has the ability to change its status from “benign diners” to parasites if the host environment facilitates its proliferation.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">12</span></a> In turn, Nicholls et al. suggested that the presence of <span class="elsevierStyleItalic">Demodex</span> could control bacterial activity, thus acting as a defense against other mite species and protecting the eyes from environmental allergens.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">13</span></a> The objective of the present study is to carry out an updated bibliographic review on <span class="elsevierStyleItalic">Demodex</span> spp. and its role as etiological agent of ocular globe and adnexa diseases, making it available to ophthalmologists and related specialists in order to facilitate searches and the differential diagnostic of this condition which in some cases is not easy to identify.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Materials and methods</span><p id="par0015" class="elsevierStylePara elsevierViewall">A bibliographic review based on various databases including PubMed central, Academic Google, Lilacs, Scopus, Science Direct and Scielo, published between 2005 and 2018, utilizing key search words such as <span class="elsevierStyleItalic">Demodex</span>, <span class="elsevierStyleItalic">folliculorum</span>, <span class="elsevierStyleItalic">brevis</span>, <span class="elsevierStyleItalic">blepharitis, cylindrical dandruff, chalazion</span>. The present review includes studies published from February 2005 up to October 2018 in English, Spanish, Turkish and Chinese focused on <span class="elsevierStyleItalic">Demodex</span> and associated pathological processes. The articles that did not relate diseases, risk factors, prevalence or incidence, treatments and diagnostics associated to <span class="elsevierStyleItalic">D. folliculorum</span> and <span class="elsevierStyleItalic">D. brevis</span>, written before 2005 were excluded. Lactophenol solution (Sigma-Aldrich<span class="elsevierStyleSup">®</span>, Saint Louis, MO, USA) was utilized in order to obtain visual identification of <span class="elsevierStyleItalic">Demodex</span> spp.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Results</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Prevalence and incidence of <span class="elsevierStyleItalic">Demodex folliculorum</span> and <span class="elsevierStyleItalic">Demodex brevis</span></span><p id="par0020" class="elsevierStylePara elsevierViewall">In 2005, Arici et al. studied 500 patients in Turkey, with only 170 exhibiting blepharitis, and reported the presence of <span class="elsevierStyleItalic">D. folliculorum</span> in 28.8% of said group as well as in 26.7% of the blepharitis-free control population.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">14</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In 2017, Murphy et al. utilized a questionnaire and carried out a search for <span class="elsevierStyleItalic">D. folliculorum</span> in 156 individuals in Ireland and found an overall prevalence of 68% as well as a positive correlation between the presence of the parasite and the expression of symptoms, with itching being the most frequently associated infestation symptom.<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">15</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">A study carried out by Wesolowska et al. in 2014 to assess the presence of <span class="elsevierStyleItalic">D. folliculorum</span> in hair follicles of hospitalized individuals and hospital workers in Poland demonstrated infestation prevalences of 54.7% and 40.0%, respectively. In addition, <span class="elsevierStyleItalic">D. folliculorum</span> was evidenced as the most frequent agent in the hair follicles of eyelashes in 81.5% of cases, compared to <span class="elsevierStyleItalic">D. brevis</span> that accounted for 34.5% of cases.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">5</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In 2015, Velasco et al. carried out a study in the Ophthalmological Unit of the Civic Hospital of Guadalajara with 100 patients in order to identify the presence of cylinders on the base of the eyelashes and on the ocular surface and found <span class="elsevierStyleItalic">D. folliculorum</span> in 92 patients exhibiting infestation prevalence of 26.7% in females and 70% in males.<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">16</span></a> In 2010, Galvis et al. carried out a study on 128 patients in the <span class="elsevierStyleItalic">Virgilio Galvis</span> Ophthalmological Center in Colombia and found a prevalence infestation of 42.1%, with 38.3% exhibiting blepharitis.<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">17</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In 2011, Yamashita et al. studied 84 patients in Brazil, with 42 exhibiting diabetes type II, and found an infestation prevalence of 27.4% in diabetes patients and 19% in the control group.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">18</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Between 2005 and 2015, at the Ophthalmology Dept. of the National Clinics Hospital in Córdoba, Argentina, Mongi et al. found a prevalence of 34% infestation in 72 examined patients. Said prevalence was higher in females with 18 positive cases against only 7 positive cases in males.<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">19</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">There are only a few studies in Chile. At Concepción University, Rivera et al. collected in 2013 samples of 32 patients and identified 10 cases of infestation in patients with palpebral disease with an age range of 61–70 years.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">20</span></a> The above data match the data reported by López et al. in 2017, who observed that 94.55% of infested patients were over 71 years of age.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">21</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The results described in the above studies agree on a higher prevalence of infestation by <span class="elsevierStyleItalic">D. folliculorum</span> in patients with ocular diseases.<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">22</span></a> This could be due to the fact that said parasites inhabit eyelash follicles. According to the data described above, the most important risk factors in the prevalence of <span class="elsevierStyleItalic">D. folliculorum</span> are age and the presence of ocular diseases, particularly blepharitis.</p><p id="par0060" class="elsevierStylePara elsevierViewall">In 2005, Rodríguez et al. studied in Spain <span class="elsevierStyleItalic">Demodex</span> spp. infestation rate in 105 healthy patients and 20 patients with chronic blepharitis. The incidence of demodecosis in control patients was 18%, finding 0.08 mites per eyelash. <span class="elsevierStyleItalic">D. folliculorum</span> was identified in 75% of patients with chronic blepharitis, finding 0.69 mites per eyelash.<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">23</span></a> Zhao et al. studied 316 medicine students in China in 2017, finding 117 (37.03%) infested individuals. The highest infestation incidence was by <span class="elsevierStyleItalic">D. folliculorum</span> with 51.28%.<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">24</span></a> Both studies suggest that <span class="elsevierStyleItalic">D. folliculorum</span> demonstrates relevant incidence in patients with blepharitis and that the mite can be observed in young individuals although it is more frequently found in elderly patients.</p><p id="par0065" class="elsevierStylePara elsevierViewall">In what concerns <span class="elsevierStyleItalic">D. brevis</span>, Wesolowska et al. studied 290 patients in Poland in 2014 and found a demodicosis prevalence of 41.0%, with 34.5% of positive cases for <span class="elsevierStyleItalic">D. brevis</span>.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">5</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Between 2016 and 2017, Zeytun et al. studied in Turkey 365 patients with blepharitis and 175 healthy patients and found that 72.3%, 0.7% and 27% were infested by <span class="elsevierStyleItalic">D. folliculorum</span>, <span class="elsevierStyleItalic">D. brevis</span> and both species, respectively.<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">25</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Mongi et al. describes that 34% of their samples were <span class="elsevierStyleItalic">D. brevis</span>, of which 10 cases were positive in females and 3 in males.<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">19</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Rivera et al. concluded in 2013 that the prevalence of <span class="elsevierStyleItalic">D. brevis</span> was lower when compared to <span class="elsevierStyleItalic">D. folliculorum</span>. Said author described that the prevalence of <span class="elsevierStyleItalic">D. brevis</span> increases with patient age: patients aged 51–60 with palpebral disease exhibited said mite with greater frequency.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">20</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">The data described in the above studies agree in a low prevalence of <span class="elsevierStyleItalic">D. brevis</span>, with age being the most important factor. On the other hand, results demonstrate that D. <span class="elsevierStyleItalic">folliculorum</span> exhibits higher prevalence than <span class="elsevierStyleItalic">D. brevis</span>.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Rodríguez et al. studied 20 individuals with chronic blepharitis, with 75% exhibiting mite infestation, with only one having <span class="elsevierStyleItalic">D. brevis</span> while the remainder had <span class="elsevierStyleItalic">D. folliculorum</span>.<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">23</span></a> On the other hand, the 2017 study by Zhao et al. on a population of 117 medicine students matched the results of previous papers in which the percentage of <span class="elsevierStyleItalic">D. folliculorum</span> (51.28%) was higher than that of <span class="elsevierStyleItalic">D. brevis</span> (24.79%). Combined infestations reached 23.93% and no preference for sex was identified.<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">24</span></a> Both studies indicate that <span class="elsevierStyleItalic">D. folliculorum</span> is the species having the highest incidence in humans.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Pathogenesis of <span class="elsevierStyleItalic">Demodex folliculorum</span> and <span class="elsevierStyleItalic">Demodex brevis</span></span><p id="par0095" class="elsevierStylePara elsevierViewall">Ocular infestation by <span class="elsevierStyleItalic">D. folliculorum</span> gives rise to anterior blepharitis and eyelash infestation.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">4</span></a> It could cause direct mechanical damage due to ocular surface irritation and inflammation derived from epithelial hyperplasia and reactive hyperkeratinization. In addition, it could deposit its eggs on the base of the eyelashes producing follicular distention and alterations in the order of eyelashes involving the loss thereof.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">4</span></a> Persistent infestation in the follicles of eyelashes gives rise to triquiasis, double eyelashes and madarosis, and could damage the corneal epithelium with corneal erosion, ulcerations and pannus in severe cases.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">4</span></a> In 2007, Kheirkhah et al. reported that anterior and posterior blepharitis could give rise in some cases to superficial dotted keratopathy, corneal neovascularization, stromal and margin infiltration, phlyctenular injuries, superficial opacities, nodular scars, limbitis and corneal perforation in extreme cases.<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">7,22</span></a> Said mites to not have an excretion organ and therefore cannot expel the material they feed on, for which reason keratin and epithelial cell deposits adhere to their eggs and give rise to cylindrical dandruff, a pathognomic sign of demodicosis.<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">22</span></a> Mite lipases and proteases found in cylindrical deposits produce ocular surface irritation and inflammation and cause dry eye, itching, irritation, foreign body feeling, tearing, blurry vision and eyelid reddening.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">4</span></a> Eyelid margin erythema could produce conjunctival inflammation giving rise to blepharoconjunctivitis and blepharokeratitis.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">26</span></a> It could also stimulate the formation of an inflammatory cascade by means of the toxins found on the surface and within their bodies.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">26</span></a> In 2017, Eser et al. reported that <span class="elsevierStyleItalic">D. folliculorum</span> could be involved in the pathogenesis of acne in patients with polycystic ovarian syndrome because they behave as opportunistic parasites in 53.7% of studied cases.<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">27</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">When <span class="elsevierStyleItalic">Demodex</span> spp. destroys epithelial cells to penetrate the dermis it stimulates Toll-type receptors and gives rise to a type IV hypersensitivity reaction.<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">28</span></a> Positive reactions have been found in patients with <span class="elsevierStyleItalic">Bacillus oleoronius</span> antigens and the presence of <span class="elsevierStyleItalic">Demodex</span> spp. in skin and eyelid lesions.<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">29</span></a> Other bacteria such as <span class="elsevierStyleItalic">Staphylococcus</span> and <span class="elsevierStyleItalic">Streptococcus</span> could be carried by <span class="elsevierStyleItalic">Demodex</span> spp.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleItalic">D. brevis</span> has been associated to marginal blepharitis because the parasite penetrates the Meibomium glands and ducts, giving rise to an inflammatory response with subsequent gland obstruction and dysfunction.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">26</span></a> In addition to the damage caused by the claws of the mite, cells undergo hyperkeratinization and hyperplasia that facilitates the formation of chalazion<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">26,30</span></a> and distention of hair follicles giving rise to cylindrical dandruff of Demodicosis infestation.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">3</span></a> Lipidic lacrimal film alteration could produce the dry eye syndrome: in ocular demodicosis, the lacrimal breakup time is altered and the Schirmer test is observed as normal.<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">31</span></a> Corneal alterations including superficial neovascularization, margin infiltration and phlyctenular lesions have been more frequently associated to <span class="elsevierStyleItalic">D. brevis</span> than <span class="elsevierStyleItalic">D. folliculorum</span> due to the fact that the former inhabits areas closer to said structure.<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">7,26</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050"><span class="elsevierStyleItalic">Demodex folliculorum</span> and <span class="elsevierStyleItalic">Demodex brevis</span> risk factors</span><p id="par0105" class="elsevierStylePara elsevierViewall">Due to the anatomic characteristics of the face, eyelids are not easily accessible for routine hygiene and thus provide a good environment for the proliferation of <span class="elsevierStyleItalic">D. folliculorum</span>.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">4</span></a> These organisms are found in the majority of human beings and exhibit higher prevalence of hair follicle infestation in comparison to <span class="elsevierStyleItalic">D. brevis</span>.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">5</span></a> There are several risk factors that facilitate infestation by <span class="elsevierStyleItalic">D. folliculorum</span>. A study published by Sȩdzikowska et al. in 2018 relating age with the risk of infestation reported that elderly adult patients were 77% more susceptible.<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">32</span></a> However, not all authors have reached the same conclusion as their results are different. In 2009, Dhingra et al. reported that infestation is higher between age 20 and 40 due to increased sebum production. In contrast, in 2011 Zhao et al. maintains that infestation increases in patients between age 12 and 30 and remains stable in elderly patients.<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">33</span></a> Other studies indicate higher probability of infestation by <span class="elsevierStyleItalic">D. folliculorum</span> in immunocompromised patients or having chronic renal insufficiency, Behçet disease, urological cancers, eyelid basal cell carcinoma, diabetes and undergoing treatment with steroids.<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">18,34</span></a> In 2018, Sędzikowska et al. did not observe significant infestation differences between individuals of both sexes,<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">32</span></a> agreeing with the results obtained by Mongi et al., in 2016.<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">19</span></a> On the other hand, patients with blepharitis had 2.5 times more risk of infestation than patients without said condition.<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">32</span></a> In 2014, Bhandari et al. established a 90% incidence in patients with anterior blepharitis.<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">22</span></a> In 2014, Wesolowska et al. demonstrated higher prevalence of 48.1% among spectacle users compared to 32.3% non-users.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">5</span></a> These results match those obtained by Tarkowski et al. in 2015, who reported infestation rates of 92.86% in contact lens-intolerant patients and observed a positive correlation between the presence of the mite and contact lens intolerance.<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">35</span></a> Additional risk factors include the presence of rosacea and seborrheic dermatitis because it alters dermal flora and enables mite proliferation, leading to a significantly higher count in patients with facial rosacea, predisposing them to blepharitis due to <span class="elsevierStyleItalic">D. folliculorum</span>.<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">29</span></a> Similar results were obtained in a study carried out in ophthalmology clinics and hospitals in Warsaw in 2018 which reported that the infestation risk in patients with rosacea was 3 times higher than in the general population.<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">32</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">It has been reported that the prevalence of <span class="elsevierStyleItalic">Demodex</span> spp. is 41.0%, with a tendency toward infesting the elderly<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">5</span></a> and individuals in direct contact with a large amount of people like health professionals who work in homes for the elderly.<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">36</span></a> It has been observed that the prevalence of <span class="elsevierStyleItalic">Demodex</span> spp. Increases with age together with increased sebum production and follicle opening which facilitates the adherence of the mite to the skin. This observation matches the results reported by Tilki et al. who argued that the elderly could have lower hygiene standards which weakens the immune system and diminishes the barrier effect of the skin.<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">37</span></a> Even though the incidence of mites increases with age, an increased amount of <span class="elsevierStyleItalic">Demodex</span> spp. has also been found in individuals with skin disorders such as acne, which is particularly prevalent in young people with stress.<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">38</span></a> The socioeconomic profile of the population could also be a risk factor because lower-income individuals could be more susceptible due to living in areas with poor hygiene such as old buildings that could allow entry of outdoors dust. However, this argument is controversial because a study carried out in 2014 did not find significant differences in the prevalence of mites in populations living in new or old buildings.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">5</span></a> Skin hygiene and cleanliness could help diminish infestation. It is recommended to keep personal hygiene items in order to diminish crossed infestation.<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">33</span></a> Individuals on immunosuppressant therapy or with immune system depressing diseases exhibited higher frequencies of demodicosis.<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">39</span></a> Similarly, a certain genetic predisposition has been described toward infestation by the ectoparasite: individuals with the human leukocyte antigen (HLA) Cw2 and Cw4 alleles could exhibit alterations in the last immune response phase (effector phase).<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">40</span></a><span class="elsevierStyleItalic">Demodex</span> spp. is also involved in facial rosacea with patients having this disease exhibiting corneal alterations.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">7</span></a> For individuals without skin disorders, a density of 0.7 mites per sq.cm of skin has been estimated, whereas in patients with diseases such as Rosaceae a density of 10.8 mites per sq.cm of skin has been observed.<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">28</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Methods for diagnosing <span class="elsevierStyleItalic">Demodex folliculorum</span> and <span class="elsevierStyleItalic">Demodex brevis</span></span><p id="par0115" class="elsevierStylePara elsevierViewall">Several techniques for diagnosing <span class="elsevierStyleItalic">Demodex</span> spp. are available, including biomicroscopy or slit lamp visualization of the condition of eyelashes, identifying cylindrical dandruff. This method can be supplemented by means of eyelash removal to inspect the mites adhered to the base thereof.<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">41</span></a> An additional identification technique is morphological analysis through confocal or light microscopy that enables the observation of the biological cycle phases of the parasite. Standard biopsy of skin surface could also be useful for the same purpose, consisting in collecting hair follicle material utilizing cyanoacrylic adhesive through the cellophane tape method. This method also has the advantage of identifying mite density.<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">42</span></a> In addition, a molecular diagnostic for identifying <span class="elsevierStyleItalic">Demodex</span> spp. can be performed by extracting and amplifying the ARNr 16S or ARNr 18S gene.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">6</span></a> According to Alexey et al., the most effective method is confocal microscopy inspection compared to light microscopy because it allows the identification of mites located in deeper skin layers as well as the assessment thereof through sucrose gradient isolation.<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">42</span></a> An additional alternative for mite count is observing autofluorescence with UV light and blue filter or through propidium iodide staining with UV light and red filter to observe dead cells that make up the structure of the mite.<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">43</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Treatment of <span class="elsevierStyleItalic">Demodex folliculorum</span> and <span class="elsevierStyleItalic">Demodex brevis</span></span><p id="par0120" class="elsevierStylePara elsevierViewall">Demodicosis could require long-term therapy because it characteristically exhibits a potential for recurrence and resistance to a broad range of drugs. Pharmacologically, several alternatives have been developed such as ivermectin, 2% metronidazole, 5% permethrin, doxycycline, benzyl benzoate and pilocarpine, characterized by diminishing the population of mite. However, none of the above therapies is 100% effective against <span class="elsevierStyleItalic">Demodex</span> spp.<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">36,44</span></a> The most efficient treatment for <span class="elsevierStyleItalic">Demodex</span> is tea tree oil, derived from the leaves of <span class="elsevierStyleItalic">Melaleuca alternifolia</span> which have terpinen-4-ol, a terpene exhibiting antimicrobial, antimycotic, antiviral, antiseptic and anti-mite properties which diminish mite overpopulation.<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">45</span></a> In 2018, Fromstein et al. suggested that in mild cases treatment should include shampoo with tea tree oil and facial washing once a day, while moderate or severe cases involve weekly treatment with highly concentrated tea tree oil during 3 consecutive weeks and face towels with tea tree oil twice a day. The latter should be applied on the edge of the eyelashes for complete coverage, which prompts the mite to migrate from eyelash hair follicles toward the skin and thus eliminating coupling, egg laying and eclosion. Patients require treatments lasting between weeks and months in order to avoid mite replication.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">26</span></a> In addition, terpinen-4-ol exhibits a broad range of antimicrobial effects that have demonstrated an inhibiting effect on hospital infestation and ocular surface contagion, including methicillin-resistant microorganisms such as <span class="elsevierStyleItalic">Staphylococcus aureus</span>, <span class="elsevierStyleItalic">Staphylococcus coagulase</span> negative and <span class="elsevierStyleItalic">Pseudomona aeruginosa</span>.<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">45</span></a> It is important to follow up the progression of the infestation because some adverse effects could arise such as ocular surface irritation with high concentrations of terpinen-4-ol<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">8</span></a> or infestation recurrence loci. In general, the mite should be eliminated after 4 weeks treatment with tea tree oil at a concentration of 38%.<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">45</span></a> An additional treatment for severe cases is the method known as microblepharoexfoliation, which comprises a rotating sponge imbibed in cleaning fluid that eliminates eggs in eyelash follicles at 3–6 months intervals.<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">46</span></a> Some cleaning products that include detergent or hypochlorous acid with antibacterial, antifungal and antiviral properties, have facilitated parasite density reduction in addition to enhancing the scarring of wounds and control of biofilms.<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">15</span></a> However, none of the treatment options have demonstrated to completely eliminates the parasite due to the chronic nature of the disorder, thus making long-term treatment a necessity.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">26</span></a></p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclusion</span><p id="par0125" class="elsevierStylePara elsevierViewall">In the course of this review it has been concluded that the prevalence of <span class="elsevierStyleItalic">Demodex</span> spp. Is variable and is associated to the type of population being studied (ethnicity, age, presence of ocular and systemic disorders, immunological status, signs and symptoms). Similarly, the majority of studies report that <span class="elsevierStyleItalic">D. folliculorum</span> is the most frequent species in adult humans and mainly affects males and is able to inhabit asymptomatic as well as symptomatic individuals as well as those exhibiting some ocular/systemic condition or immunology compromise. Likewise, when observing a patient with blepharitis or another ocular surface infectious disease that is not resolved with frequently used ophthalmological antibacterial medicaments, the search for <span class="elsevierStyleItalic">Demodex</span> spp. should be considered, taking into account the pathognomic characteristics of the condition, predisposing factors, recurrence and mite resistance to standard treatments. The present review could be of help and be useful as an updated reference for many ophthalmologists, medical technicians in ophthalmology and other health professionals addressing this problem which, as reported, has demonstrated to be highly prevalent in our environment in addition to being diagnosed at later stages and with complicated treatment requiring ongoing follow-up.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Funding</span><p id="par0130" class="elsevierStylePara elsevierViewall">Medical Technology College, Austral University of Chile, Puerto Montt Campus, Puerto Montt vicerectorate Puerto Montt, Austral University of Chile, Puerto Montt, Chile.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflict of interests</span><p id="par0135" class="elsevierStylePara elsevierViewall">No conflict of interests was declared by the authors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1213833" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1129507" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1213832" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1129508" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Materials and methods" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Results" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Prevalence and incidence of Demodex folliculorum and Demodex brevis" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Pathogenesis of Demodex folliculorum and Demodex brevis" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Demodex folliculorum and Demodex brevis risk factors" ] 3 => array:2 [ "identificador" => "sec0035" "titulo" => "Methods for diagnosing Demodex folliculorum and Demodex brevis" ] 4 => array:2 [ "identificador" => "sec0040" "titulo" => "Treatment of Demodex folliculorum and Demodex brevis" ] ] ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Conclusion" ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflict of interests" ] 10 => array:2 [ "identificador" => "xack414941" "titulo" => "Acknowledgments" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-01-15" "fechaAceptado" => "2019-04-01" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1129507" "palabras" => array:6 [ 0 => "Demodex" 1 => "<span class="elsevierStyleItalic">Folliculorum</span>" 2 => "<span class="elsevierStyleItalic">Brevis</span>" 3 => "Blepharitis" 4 => "Cylindrical dandruff" 5 => "Chalazion" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1129508" "palabras" => array:6 [ 0 => "Demodex" 1 => "<span class="elsevierStyleItalic">Folliculorum</span>" 2 => "<span class="elsevierStyleItalic">Brevis</span>" 3 => "Blefaritis" 4 => "Caspa cilíndrica" 5 => "Chalazión" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Demodex folliculorum</span> and <span class="elsevierStyleItalic">Demodex brevis</span> are ectoparasites that inhabit the skin of humans. They have been related to alterations in the ocular surface, such as, dysfunction of Meibomian glands, blepharitis, chalazion, etc. Ocular demodicosis is characterized by the pathognomonic presence of cylindrical dandruff at the base of the eyelashes, and various symptoms including, among others, itching, lacrimation, and hyperaemia. A bibliographic review was carried out on the role of <span class="elsevierStyleItalic">Demodex</span> spp. in ocular disease, including publications made by the scientific society between 2005 and 2018. A significant relationship was found between prevalence and incidence of <span class="elsevierStyleItalic">Demodex</span> spp. in eye diseases. <span class="elsevierStyleItalic">D. folliculorum</span> is usually found more frequently than <span class="elsevierStyleItalic">D. brevis</span> in ocular infestation, with the prevalence or incidence of infestation by both species increasing with the age of the patient. In patients with blepharitis or other infectious diseases of the ocular surface, unresolved with antibacterial treatment, the search for <span class="elsevierStyleItalic">Demodex</span> spp. should be considered.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Demodex folliculorum</span> y <span class="elsevierStyleItalic">Demodex</span><span class="elsevierStyleItalic">brevis</span> son ectoparásitos que habitan en la piel de los seres humanos. Han sido relacionados con alteraciones en la superficie ocular, tales como disfunción de glándulas de Meibomio, blefaritis, chalazión, etc. La demodicosis ocular se caracteriza por la presencia patognomónica de caspa cilíndrica en la base de las pestañas y diversos síntomas como picazón, lagrimeo e hiperemia, entre otros. Se realizó una revisión bibliográfica del rol de <span class="elsevierStyleItalic">Demodex</span> spp. en la enfermedad ocular, incluyéndose publicaciones científicas entre los años 2005-2018. Se registró una asociación importante de prevalencia e incidencia de <span class="elsevierStyleItalic">Demodex</span> spp. en enfermedades oculares. <span class="elsevierStyleItalic">D. folliculorum</span> se encontró con mayor frecuencia que <span class="elsevierStyleItalic">D. brevis</span> en la infestación ocular, incrementándose la prevalencia o incidencia de infestación por ambas especies con la edad del paciente. Se sugiere que en pacientes con blefaritis, u otra enfermedad infecciosa de la superficie ocular no resuelta con tratamiento antibacteriano, debería plantearse la búsqueda de <span class="elsevierStyleItalic">Demodex</span> spp.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Moris García V, Valenzuela Vargas G, Marín Cornuy M, Aguila Torres P. Demodicosis ocular: una revisión. Arch Soc Esp Oftalmol. 2019;94:316–322.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 539 "Ancho" => 805 "Tamanyo" => 50320 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Demodex</span> spp. stained with lactophenol solution. 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