Effects and safety of perfluorohexyloctane on the eye surface and corneal endothelium | Archivos de la Sociedad Española de Oftalmología (English Edition)

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Mateo Orobia, A. Blasco-Martinez, P. Rodríguez-Ausín, L.E. Pablo Júlvez, N. Güemes Villahoz, E. del Prado Sanz, M. Satué Palacián, J.M. Benítez-del-Castillo" "autores" => array:8 [ 0 => array:3 [ "nombre" => "A.J." "apellidos" => "Mateo Orobia" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 1 => array:4 [ "nombre" => "A." "apellidos" => "Blasco-Martinez" "email" => array:1 [ 0 => "ablascom@salud.aragon.es" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "P." "apellidos" => "Rodríguez-Ausín" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "L.E." 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"apellidos" => "Benítez-del-Castillo" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] 1 => array:2 [ "etiqueta" => "f" "identificador" => "aff0030" ] ] ] ] "afiliaciones" => array:6 [ 0 => array:3 [ "entidad" => "Grupo de Investigación Miguel Servet Oftalmología (GIMSO), Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Zaragoza, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Oftalmología, Hospital Provincial Nuestra Señora de Gracia, Zaragoza, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Oftalmología, Hospital Universitario de Torrejón de Ardoz, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Catedrático, Universidad de Zaragoza, Zaragoza, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Departamento de Oftalmología, Hospital Clínico San Carlos, Madrid, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Catedrático, Universidad Complutense de Madrid, Madrid, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Efectos y seguridad del perfluorohexiloctano en la superficie ocular y el endotelio corneal" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1051 "Ancho" => 2166 "Tamanyo" => 86182 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Subjective evaluations. DED: dry eye disease; EDE: evaporative dry eye." ] ] ] "textoCompleto" => "IntroductionLiquid perfluorocarbons (LPFC) were widely used in vitreoretinal surgery as buffer for the retina to recover its normal anatomical position in the least traumatic way. Some authors have shown LPFCs toxicity in this type of surgery in terms of cellular damage, inflammatory reactions such as compression and destruction of their normal structure, disorganization, photoreceptor degenerative alterations, macrophage activation and cell number reduction, although it is not yet clear whether this is due to toxic or mechanical damage, as a progressive effect proportional to the time of contact with this substance has been observed.<a class="elsevierStyleCrossRefs" href="#bib0005">1–6</a> In an attempt to avoid these effects, semi-fluorinated alkanes (SFAs) that combine a perfluorocarbon with a hydrocarbon segment were developed in order to decrease the fluorinated part in the molecular chain and diminish density and viscosity, One of these SFAs is perfluorohexyloctane (F6H8), which due to its lower specific gravity has been widely used in vitreoretinal surgery as LPFC<a class="elsevierStyleCrossRef" href="#bib0035">7</a> substitute. Studies in rabbits with vitreous replacement did not show significant retinal alterations in optical and electron microscopy, but according to some studies<a class="elsevierStyleCrossRefs" href="#bib0005">1–3,8,9</a> clinical experience yields different results.A common problem when injecting LPFC in vitreoretinal surgery occurred in aphakic eyes, since this substance could move to the anterior chamber. Moreira et al.10 studied the effect of F6H8 in the anterior chamber of rabbit eyes and observed corneal edema, neovascularization, conjunctival inflammation and small bubbles in the cornea, possibly due to corneal endothelium toxicity.<a class="elsevierStyleCrossRefs" href="#bib0050">10,11</a>F6H8 has been recently used as an ocular surface waterproofing compound in conditions such as dry eye disease (DED), due to its low viscosity, surface tension and its ability to stop evaporation of fluid that comes in contact with it.<a class="elsevierStyleCrossRefs" href="#bib0060">12,13</a> The objective of DED treatment is to restore the tear film and ocular surface homeostasis, guided by the DED etiology and predominant type, in addition to requiring adequate management of the inflammation that occurs with this illness. However, intolerance to stabilizing agents or preservatives can cause inflammation, impaired tear film stability and discontinuation of treatment.<a class="elsevierStyleCrossRefs" href="#bib0060">12,15</a> F6H8 treatment does not need to be combined with a preservative since it is a non-aqueous liquid and therefore microbial growth is not possible. Furthermore, F6H8 demonstrates significant diffusion characteristics that reduce shear forces between surfaces and dissolve lipids due to their amphiphilic nature, without the need to form oil-water suspensions.In previous studies, F6H8 has been shown to be safe in terms of visual acuity and intraocular pressure, and only shows a mild to moderate hypersensitivity response.<a class="elsevierStyleCrossRefs" href="#bib0060">12,13,18</a> However, the potential toxic effects and corneal endothelium safety, in terms of cellular damage when used as a treatment for DED, remain unclear. The present study analyzed the possible toxic effects on the cornea and its endothelium, as well as the improvement in ocular surface and symptoms parameters.MethodsAccording to a preliminary study carried out by the authors' group, the necessary sample size was calculated to detect differences of at least 0.5 points in the staining scales, 5 μm in central corneal thickness (CCC) and 10% in endothelium parameters, applying a bilateral test with an α risk of 5% and a β risk of 10% (that is, with a 90% power). With these data it was concluded that at least 82 eyes (41 patients) would be necessary. The study included 45 patients (90 eyes) 60.84 ± 12.21 years old (between 33 and 80 years old), 91.5% were females and 8.5% males, following the second report of Tear Film and Ocular Surface Society (TFOS), the Dry Eye WorkShop (DEWS II)<a class="elsevierStyleCrossRef" href="#bib0080">16</a> study guidelines. The different etiologies and their proportion in the study for DED were as follows: evaporative dry eye (EDE) 51.35%, mixed dry eye 25.78, post-phacoemulsification 8.67%, post-Lasik 8.5% and post-infection 5.7%. Inclusion criteria were: patients older than 18 years, diagnosed with any symptomatic DED etiology, with a corneal staining of at least grade 1 (Oxford scale) and only artificial tears as previous treatment. EDE and mixed dry eye were specified. Exclusion criteria were: previous eye treatments other than artificial tears, previous blepharitis diagnosis, glaucoma and any other eye disease, use of contact lenses, previous eye surgery, systemic treatments that may affect the eye surface or EDE (such as benzodiazepines, antidepressants or hormonal treatment), difficulty understanding the treatment and inability to attend visits. All patients began treatment with 4  drops a day of F6H8 (EvoTears®, Brill-Pharma, Barcelona, Spain) in a 6  month longitudinal prospective multicenter study. All patients were recruited in corresponding ocular surface consultations (Torrejón de Ardoz University Hospital, San Carlos Clinical Hospital in Madrid and Miguel Servet University Hospital in Zaragoza), with informed consent to participate in the study. Three visits were scheduled: baseline (D0), 3  months (M3) and 6  months (M6) of treatment. All procedures adhered to Declaration of Helsinki principles, and the study feasibility was approved by local ethics committee (Ethics Committee for Scientific Research in Aragon). In all the scheduled study visits, the following clinical variables were collected in this order: 5 μl with micropipette, waiting one minute to take corneal staining measurements with fluorescein (20 mg/mL) using the National Eye Institute/Industry Workshop scale (NEI, between 0 and 15 points). Conjunctival variables with 0.5% lysamine green using the Oxford scale (between 0 and 4 points) with the same micropipette, and corneal and endothelial parameters such as central corneal thickness (CCC), cell density, coefficient of variation, hexagonality (HEX) and average cell area using Topcon SP-1 P specular microscope (Topcon Positioning Systems Inc., Tokyo, Japan). All measurements were taken in the same room, by the same researcher at room temperature between 21 and 25 °C and humidity between 37 and 46% in each center. Endothelial variables were analyzed using automated imaging and a minimum of 20 cells provided by specular microscope software. Compliance was assessed in each visit and treatment satisfaction was measured at the end of the study. The distinction between compliance and non-compliance was assessed by means of a self-report in which patients were asked whether they administered the treatment of 4 drops per day (classified as "compliant") or if they did not administer them correctly (classified as "noncompliant"). Non-compliant patients were not included in the statistical analysis of visits M3 and M6. Patients were divided in 2 different groups, according to their D0 corneal staining (NEI group ≤ 3 and NEI group> 3) to determine any differences in endothelial toxicity according to the epithelial barrier permeability degree. In statistical analysis, both eyes were considered independent in terms of corneal staining. All data was documented in an Excel spreadsheet and analyzed with the IBM® SPSS® Statistics 23.0 program (IBM, New York, USA), using the t for Student test to determine average differences in related samples. To correlate treatment compliance with the final subjective evaluation, Pearson's χ<a class="elsevierStyleCrossRef" href="#bib0010">2</a> test was used. P values <0.05 were considered statistically relevant.Results<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows descriptive data of the variables studied in the selection visit (D0), taking into account the distinction between compliant and non-compliant patients, which was evaluated in the 2 following visits. Of the 45 patients who started the study, 32 were classified as compliant (71.1%) and 13 as non-compliant (28.9%). Statistically significant differences were observed in both groups in terms of coefficient of variation, HEX and CCC. Significant differences were also found between DED types and corneal staining (1.54 ± 2.13 in EDE and 4.13 ± 4.43 in other types, p =  0.002), between DED and HEX (66.33 ± 14.70% in EDE and 44.49 ± 15.91% in other types, p < 0.001) and between DED and CCC (554.83 ± 28.33 μm in EDE y 529.07 ± 43.64 μm in other types, p =  0.004). When comparing paired differences between variables in corneal and conjunctival staining in compliant patients (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), a statistically significant decrease of 0.84 ± 1.95 points on the NEI scale in M3 (p =  0.001) and 1.65 ± 2.42 points in M6 (p < 0.001), compared to D0, were observed. No significant difference was found in the conjunctival staining with lysamine green in either M3 or M6 (p =  0.267 in M3 and p =  0.319 in M6). Paired differences in endothelial parameters between D0 and M6 did not reveal statistically significant differences (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). However, for endothelial parameters, patients with a higher degree of corneal staining at D0 (NEI > 3) were statistically analyzed separately compared to those who had a corneal staining NEI ≤ 3, comparing D0 with M6. Statistically significant differences were observed only in CCC, which revealed a decrease of 6.90 ± 6.64 μm in patients with NEI > 3 (p =  0.009). At the end of the study a treatment satisfaction questionnaire was given to all patients (compliant and non-compliant). <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> shows the subjective evaluations of these patients according to their DED etiology (EDE or other types). There were no statistically significant differences in percentages of patients that reported feeling the same or worse and those who reported feeling better (p < 0.729). Treatment compliance was significantly correlated with the final subjective evaluation using Pearson's χ<a class="elsevierStyleCrossRef" href="#bib0010">2</a> test (p =  0.002), so that 57.41% of compliant patients reported feeling better, compared to 12.50% of non-compliant patients. <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows paired differences in endothelial parameters according to corneal staining degree.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>DiscussionSFAs are colorless, physically, chemically and physiologically inert liquids, with substantially reduced densities (between 1.1 and 1.7 g/cm<a class="elsevierStyleCrossRef" href="#bib0015">3</a>) and very low surface tensions. They can be used as medicine solvents or solubilizers.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> According to the current DEWS II report, DED classification includes a wide range of etiologies that can be divided in 2 subtypes: aqueous-deficient dry eye and EDE, but they often overlap. The classification algorithm and treatment decisions are more favorable to EDE than aqueous-deficient dry eye, since EDE is more common.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> The main cause of this condition is Meibomian glands dysfunction, although there are other anomalies that can cause it, such as mucin deficiency, contact lense use or changes related to blinking.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> The main goal of this study was to evaluate F6H8s safety and efficacy on the ocular surface and corneal endothelium in patients diagnosed with DED of various etiologies. To date, no endothelial safety studies have been conducted in patients treated with topical SFAs. From the 45 patients that started the study, 32 were classified as compliant (71.1%) and 13 as non-compliant (28.9%). In some cases, this was due to the fact that they were unable to pay for treatment. At the start of the study, the non-compliant group had worse endothelial values in terms of coefficient of variation, HEX, and CCC, and no changes were observed in the average corneal staining level, although this also appeared to be worse. Throughout the study, a statistically significant improvement in corneal staining was observed from M3 which became even more evident in M6, indicating that this compound is effective in treating keratitis caused by DED. However, no statistically significant improvement in conjunctival staining was observed. This may be due to the fact that F6H8 has a different bioadhesive nature in damaged corneal epithelium and damaged conjunctival epithelium, in addition to worse area coverage and slower conjunctival cell recovery. On the other hand, according to previous research,<a class="elsevierStyleCrossRefs" href="#bib0050">10,11</a> if F6H8 had caused corneal endothelium toxicity, an increase in corneal thickness or some alteration in the endothelium should have been observed as a sign of endothelial dysfunction. The results of this study show that F6H8, regardless of corneal penetration, does not cause toxicity to the corneal endothelium, since there were no significant changes in the variables collected after 6  months of treatment. Moreover, the beneficial effects on corneal epithelial barrier recovery (shown by corneal staining reduction) appear to cause a significant decrease in patient CCC with a higher degree of corneal staining at D0, in contrast with patients who did not have a high degree of corneal staining, for whom CCC showed no significant changes. This may also indicate the existence of subclinical corneal edema in conditions such as DED, which presents with keratitis and improves when the ocular surface is treated. A less likely, but still possible explanation, is that Evotears® (Brill Pharma SL, Barcelona, Spain) has a positive or protective effect on endothelial function, but further studies would be needed to research this. Furthermore, at the end of the study, 86.48% of patients reported feeling the same (40.54%) or better (45.94%) after treatment, compared to 13.52% who reported feeling worse. Given F6H8s waterproofing capabilities and its ability to retain water, we expect to find differences in ocular surface improvement, satisfaction degree and compliance according to the DED etiology, although it is more effective for EDE. Nevertheless, the treatment improved EDE and other types of DED. However, <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> shows a slight trend towards greater subjective improvement (not statistically significant) in patients with EDE. In the present study, all patients diagnosed with EDE presented Meibomian glands dysfunction, so it is possible that the treatment efficacy in this case is due to F6H8s dispersing properties, caused by its low surface tension (19.65 mN/m), which stabilizes tear films that lack an optimal lipid layer.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> Lipids that obstruct the ducts could potentially be dissolved with F6H8, allowing them to reopen. More studies are needed to test these hypotheses. This study did not differentiate DED types and etiologies, since the focus was on a new generic treatment and its consequences for all symptomatic DED, only distinguishing EDE and others. However, more studies are needed to differentiate the effectiveness of this treatment according to these variables.Ultimately, in the present study, F6H8s  efficacy and safety have shown that it is a useful treatment option for patients with DED, since treatment did not change the measured endothelial variables and produced a significant improvement in corneal staining, as well as a decrease in possible subclinical corneal edema due to DED.Conflict of interestsNone." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1407060" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1287290" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1407061" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1287291" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-01-16" "fechaAceptado" => "2020-05-19" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1287290" "palabras" => array:5 [ 0 => "EvoTears®" 1 => "Perfluorohexyloctane" 2 => "Endothelium" 3 => "Dry eye disease" 4 => "Ocular surface" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1287291" "palabras" => array:5 [ 0 => "Evotears" 1 => "Perfluorohexiloctano" 2 => "Endotelio" 3 => "Enfermedad de ojo seco" 4 => "Superficie ocular" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo evaluate the effects and safety of topical drops of perfluorohexyloctane (F6H8) on the ocular surface and the corneal endothelium. MethodsForty-five patients (90 eyes) diagnosed with dry eye disease (DED) were recruited and prescribed treatment with F6H8 as part of a six-month prospective multicentre study. Variables in corneal staining were documented using the National Eye Institute/Industry Workshop (NEI) scale. The conjunctival variables included using the Oxford scale, as well as corneal parameters, such as central corneal thickness, cell density, coefficient of variation, hexagonality, and mean cell area, at the start of the study, and at three months and six months. Compliance and satisfaction with the treatment were measured. ResultsF6H8 drops reduced mean corneal staining based on the NEI scale in compliant patients to a mean of −0.84 ± 1.95 at three months (P = .001) and to −1.65 ± 2.42 at six months (P < .001). Conjunctival staining at six months showed a mean decrease of −0.13 (P = .319). The endothelial parameters did not show a significant difference, in contrast to the central corneal thickness that showed a statistically significant decrease (545.30 ± 32.25 at the start of the study to 538.40 ± 31.36 after six months, P = .009). At the end of the study, 46% of patients reported feeling subjectively better, 40.5% felt the same, and 13.5% felt subjectively worse. ConclusionsTopical treatment with F6H8 for DED did not alter the measured variables of the corneal endothelium, but showed improvement in corneal staining and satisfaction." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoEvaluar los efectos y la seguridad del perfluorohexiloctano (F6H8) tópico en la superficie ocular y el endotelio corneal. MétodosCuarenta y cinco pacientes (90 ojos) diagnosticados de Enfermedad de Ojo Seco (EOS) fueron reclutados y se les prescribió tratamiento con F6H8 durante seis meses. Las variables en la tinción corneal se documentaron usando la escala National Eye Institute/Industry Workshop (NEI), las variables conjuntivales usando la escala Oxford, y los parámetros corneales como el espesor corneal central, la densidad celular, el coeficiente de variación, la hexagonalidad y el área celular promedio, al inicio del estudio, a los tres meses y a los seis meses. Se evaluó también el cumplimiento y la satisfacción. Resultadosel tratamiento con F6H8 redujo la tinción corneal promedio en pacientes cumplidores a una media de -0,84 ± 1,95 a los tres meses (p = 0,001) y a -1,65 ± 2,42 a los seis meses (p < 0,001). La tinción conjuntival a los seis meses mostró una disminución promedio de -0,13 (p = 0,319). Los parámetros endoteliales no mostraron diferencia significativa, excepto el espesor corneal central que mostró una disminución estadísticamente significativa (545,30 ± 32,25μm al comienzo del estudio y 538,40 ± 31,36μm tras seis meses, p = 0,009). Al final del estudio, el 46% de los pacientes informaron sentirse subjetivamente mejor, el 40,5% no sintió cambios y el 13,5% se sintió subjetivamente peor. ConclusionesEl tratamiento tópico con F6H8 para EOS no alteró las variables medidas del endotelio corneal, mostrando mejoría en la tinción corneal y en la satisfacción." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Mateo Orobia AJ, Blasco-Martinez A, Rodríguez-Ausín P, Pablo Júlvez LE, Güemes Villahoz N, del Prado Sanz E, et al. Efectos y seguridad del perfluorohexiloctano en la superficie ocular y el endotelio corneal. Arch Soc Esp Oftalmol. 2020;95:538–543." ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1248 "Ancho" => 1339 "Tamanyo" => 65154 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Paired differences in corneal staining. M3: month 3; M6: month 6." ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1051 "Ancho" => 2166 "Tamanyo" => 86182 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Subjective evaluations. DED: dry eye disease; EDE: evaporative dry eye." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Asterisks mark statistically significant differences. AVG: average cell area; CV: coefficient of variation; CD: endothelial cell density; SD: standard deviation; CCC, central corneal thickness; HEX: percentage of cellular hexagonality; NEI: National Eye Institute (scale used for corneal staining with fluorescein); LG: lysamine green (Oxford scale used for corneal/conjunctival staining)." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Average ± SD \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Confidence interval of 95%</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">p \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Lower limit \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Upper limit \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NEI (0−15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Complying \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.79 ± 3.87 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.222 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non complying \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.69 ± 4.08 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.81 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LG (0−4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Complying \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.34 ± 1.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.69 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.708 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non complying \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.79 ± 3.87 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CD (cells/mm2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Complying \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2296.68 ± 521.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2157.43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2428.48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.710 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non complying \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2456.75 ± 511.86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2220.23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2722.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CV (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Complying \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30.98 ± 6.66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29.38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32.80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.024* \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non complying \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32.13 ± 5.21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29.77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34.67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HEX (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Complying \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">55.77 ± 17.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.001* \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non complying \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39.88 ± 17.70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32.11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AVG (μm2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Complying \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">466.17 ± 139.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">431.49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">503.49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.664 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non complying \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">425.06 ± 93.34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">377.40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">470.21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CCC (μm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Complying \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">545.85 ± 40.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">534.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">556.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.010* \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non complying \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">512.13 ± 30.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">497.23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">527.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2413030.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Descriptive data and average comparison between complying and non-complying patients with staining and endothelial parameters." ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "AVG: average cell area; CV: coefficient of variation; D0: day 0; CD: endothelial cell density; SD: standard deviation; CCC, central corneal thickness; HEX: percentage of cellular hexagonality; M6: month 6." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Average difference ± SD \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">T Value \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CD D0 vs. M6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.65 ± 297.53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.209 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.836 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CV D0 vs. M6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−1.23 ± 6.65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−1.083 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.287 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HEX D0 vs. M6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−2.18 ± 14.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.883 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.384 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AVG D0 vs. M6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.41 ± 77.79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.556 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.582 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CCC D0 vs. M6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.09 ± 19.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.946 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.351 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2413029.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Paired differences in endothelial parameters at 6 months (compliant patients)." ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0025" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Asterisks mark statistically significant differences. AVG: average cell area; CV: coefficient of variation; D0: day 0; CD: endothelial cell density; SD: standard deviation; CCC, central corneal thickness; HEX: percentage of cellular hexagonality; M6: month 6." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">NEI ≤ 3</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">NEI > 3</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Average difference ± SD \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">T Value \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Average difference ± SD \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">T Value \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CD D0 vs. M6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.36 ± 300.96 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.064 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.949 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.89 ± 295.69 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.437 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.665 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CV D0 vs. M6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−1.39 ± 6.66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−1.205 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.237 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.33 ± 7.65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.227 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.823 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HEX D0 vs. M6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−2.09 ± 14.58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.824 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.416 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.56 ± 6.78 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.426 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.674 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AVG D0 vs. M6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.73 ± 78.77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.636 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.529 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−17.07 ± 134.48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.660 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.515 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; 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Effects and safety of perfluorohexyloctane on the eye surface and corneal endothelium

Efectos y seguridad del perfluorohexiloctano en la superficie ocular y el endotelio corneal

A.J. Mateo Orobiaa,b, A. Blasco-Martineza,b,

Corresponding author

ablascom@salud.aragon.es

Corresponding author.

, P. Rodríguez-Ausínc, L.E. Pablo Júlveza,d, N. Güemes Villahoze, E. del Prado Sanza,b, M. Satué Palaciána, J.M. Benítez-del-Castilloe,f

a Grupo de Investigación Miguel Servet Oftalmología (GIMSO), Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Zaragoza, Spain

b Servicio de Oftalmología, Hospital Provincial Nuestra Señora de Gracia, Zaragoza, Spain

c Servicio de Oftalmología, Hospital Universitario de Torrejón de Ardoz, Madrid, Spain

d Catedrático, Universidad de Zaragoza, Zaragoza, Spain

e Departamento de Oftalmología, Hospital Clínico San Carlos, Madrid, Spain

f Catedrático, Universidad Complutense de Madrid, Madrid, Spain

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neovascularization&#44; conjunctival inflammation and small bubbles in the cornea&#44; possibly due to corneal endothelium toxicity&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">F6H8 has been recently used as an ocular surface waterproofing compound in conditions such as dry eye disease &#40;DED&#41;&#44; due to its low viscosity&#44; surface tension and its ability to stop evaporation of fluid that comes in contact with it&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13</span></a> The objective of DED treatment is to restore the tear film and ocular surface homeostasis&#44; guided by the DED etiology and predominant type&#44; in addition to requiring adequate management of the inflammation that occurs with this illness&#46; However&#44; intolerance to stabilizing agents or preservatives can cause inflammation&#44; impaired tear film stability and discontinuation of treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;15</span></a> F6H8 treatment does not need to be combined with a preservative since it is a non-aqueous liquid and therefore microbial growth is not possible&#46; Furthermore&#44; F6H8 demonstrates significant diffusion characteristics that reduce shear forces between surfaces and dissolve lipids due to their amphiphilic nature&#44; without the need to form oil-water suspensions&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In previous studies&#44; F6H8 has been shown to be safe in terms of visual acuity and intraocular pressure&#44; and only shows a mild to moderate hypersensitivity response&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13&#44;18</span></a> However&#44; the potential toxic effects and corneal endothelium safety&#44; in terms of cellular damage when used as a treatment for DED&#44; remain unclear&#46; The present study analyzed the possible toxic effects on the cornea and its endothelium&#44; as well as the improvement in ocular surface and symptoms parameters&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">According to a preliminary study carried out by the authors&#39; group&#44; the necessary sample size was calculated to detect differences of at least 0&#46;5 points in the staining scales&#44; 5&#8239;&#956;m in central corneal thickness &#40;CCC&#41; and 10&#37; in endothelium parameters&#44; applying a bilateral test with an &#945; risk of 5&#37; and a &#946; risk of 10&#37; &#40;that is&#44; with a 90&#37; power&#41;&#46; With these data it was concluded that at least 82 eyes &#40;41 patients&#41; would be necessary&#46; The study included 45&#8239;patients &#40;90 eyes&#41; 60&#46;84&#8239;&#177;&#8239;12&#46;21 years old &#40;between 33 and 80 years old&#41;&#44; 91&#46;5&#37; were females and 8&#46;5&#37; males&#44; following the second report of <span class="elsevierStyleItalic">Tear Film and Ocular Surface Society</span> &#40;TFOS&#41;&#44; the <span class="elsevierStyleItalic">Dry Eye WorkShop</span> &#40;DEWS II&#41;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> study guidelines&#46; The different etiologies and their proportion in the study for DED were as follows&#58; evaporative dry eye &#40;EDE&#41; 51&#46;35&#37;&#44; mixed dry eye 25&#46;78&#44; post-phacoemulsification 8&#46;67&#37;&#44; post-Lasik 8&#46;5&#37; and post-infection 5&#46;7&#37;&#46; Inclusion criteria were&#58; patients older than 18 years&#44; diagnosed with any symptomatic DED etiology&#44; with a corneal staining of at least grade 1 &#40;Oxford scale&#41; and only artificial tears as previous treatment&#46; EDE and mixed dry eye were specified&#46; Exclusion criteria were&#58; previous eye treatments other than artificial tears&#44; previous blepharitis diagnosis&#44; glaucoma and any other eye disease&#44; use of contact lenses&#44; previous eye surgery&#44; systemic treatments that may affect the eye surface or EDE &#40;such as benzodiazepines&#44; antidepressants or hormonal treatment&#41;&#44; difficulty understanding the treatment and inability to attend visits&#46; All patients began treatment with 4&#8239; drops a day of F6H8 &#40;EvoTears&#174;&#44; Brill-Pharma&#44; Barcelona&#44; Spain&#41; in a 6&#8239; month longitudinal prospective multicenter study&#46; All patients were recruited in corresponding ocular surface consultations &#40;Torrej&#243;n de Ardoz University Hospital&#44; San Carlos Clinical Hospital in Madrid and Miguel Servet University Hospital in Zaragoza&#41;&#44; with informed consent to participate in the study&#46; Three visits were scheduled&#58; baseline &#40;D0&#41;&#44; 3&#8239; months &#40;M3&#41; and 6&#8239; months &#40;M6&#41; of treatment&#46; All procedures adhered to Declaration of Helsinki principles&#44; and the study feasibility was approved by local ethics committee &#40;Ethics Committee for Scientific Research in Aragon&#41;&#46; In all the scheduled study visits&#44; the following clinical variables were collected in this order&#58; 5&#8239;&#956;l with micropipette&#44; waiting one minute to take corneal staining measurements with fluorescein &#40;20&#8239;mg&#47;mL&#41; using the <span class="elsevierStyleItalic">National Eye Institute&#47;Industry Workshop</span> scale &#40;NEI&#44; between 0 and 15 points&#41;&#46; Conjunctival variables with 0&#46;5&#37; lysamine green using the Oxford scale &#40;between 0 and 4 points&#41; with the same micropipette&#44; and corneal and endothelial parameters such as central corneal thickness &#40;CCC&#41;&#44; cell density&#44; coefficient of variation&#44; hexagonality &#40;HEX&#41; and average cell area using Topcon SP-1&#8239;P specular microscope &#40;Topcon Positioning Systems Inc&#46;&#44; Tokyo&#44; Japan&#41;&#46; All measurements were taken in the same room&#44; by the same researcher at room temperature between 21 and 25&#8239;&#176;C and humidity between 37 and 46&#37; in each center&#46; Endothelial variables were analyzed using automated imaging and a minimum of 20 cells provided by specular microscope software&#46; Compliance was assessed in each visit and treatment satisfaction was measured at the end of the study&#46; The distinction between compliance and non-compliance was assessed by means of a self-report in which patients were asked whether they administered the treatment of 4 drops per day &#40;classified as &#34;compliant&#34;&#41; or if they did not administer them correctly &#40;classified as &#34;noncompliant&#34;&#41;&#46; Non-compliant patients were not included in the statistical analysis of visits M3 and M6&#46; Patients were divided in 2&#8239;different groups&#44; according to their D0 corneal staining &#40;NEI group &#8804; 3 and NEI group&#62; 3&#41; to determine any differences in endothelial toxicity according to the epithelial barrier permeability degree&#46; In statistical analysis&#44; both eyes were considered independent in terms of corneal staining&#46; All data was documented in an Excel spreadsheet and analyzed with the IBM&#174; SPSS&#174; Statistics 23&#46;0 program &#40;IBM&#44; New York&#44; USA&#41;&#44; using the t for Student test to determine average differences in related samples&#46; To correlate treatment compliance with the final subjective evaluation&#44; Pearson&#39;s &#967;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> test was used&#46; P values &#60;0&#46;05 were considered statistically relevant&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0025" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows descriptive data of the variables studied in the selection visit &#40;D0&#41;&#44; taking into account the distinction between compliant and non-compliant patients&#44; which was evaluated in the 2&#8239;following visits&#46; Of the 45 patients who started the study&#44; 32 were classified as compliant &#40;71&#46;1&#37;&#41; and 13 as non-compliant &#40;28&#46;9&#37;&#41;&#46; Statistically significant differences were observed in both groups in terms of coefficient of variation&#44; HEX and CCC&#46; Significant differences were also found between DED types and corneal staining &#40;1&#46;54&#8239;&#177;&#8239;2&#46;13 in EDE and 4&#46;13&#8239;&#177;&#8239;4&#46;43 in other types&#44; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239; 0&#46;002&#41;&#44; between DED and HEX &#40;66&#46;33 &#177; 14&#46;70&#37; in EDE and 44&#46;49 &#177; 15&#46;91&#37; in other types&#44; <span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;001&#41; and between DED and CCC &#40;554&#46;83 &#177; 28&#46;33&#8239;&#956;m in EDE y 529&#46;07&#8239;&#177;&#8239;43&#46;64&#8239;&#956;m in other types&#44; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239; 0&#46;004&#41;&#46; When comparing paired differences between variables in corneal and conjunctival staining in compliant patients &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#44; a statistically significant decrease of 0&#46;84&#8239;&#177;&#8239;1&#46;95 points on the NEI scale in M3 &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239; 0&#46;001&#41; and 1&#46;65 &#177; 2&#46;42 points in M6 &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;001&#41;&#44; compared to D0&#44; were observed&#46; No significant difference was found in the conjunctival staining with lysamine green in either M3 or M6 &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239; 0&#46;267 in M3 and <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239; 0&#46;319 in M6&#41;&#46; Paired differences in endothelial parameters between D0 and M6 did not reveal statistically significant differences &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; However&#44; for endothelial parameters&#44; patients with a higher degree of corneal staining at D0 &#40;NEI&#8239;&#62;&#8239;3&#41; were statistically analyzed separately compared to those who had a corneal staining NEI&#8239;&#8804;&#8239;3&#44; comparing D0 with M6&#46; Statistically significant differences were observed only in CCC&#44; which revealed a decrease of 6&#46;90&#8239;&#177;&#8239;6&#46;64&#8239;&#956;m in patients with NEI&#8239;&#62;&#8239;3 &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239; 0&#46;009&#41;&#46; At the end of the study a treatment satisfaction questionnaire was given to all patients &#40;compliant and non-compliant&#41;&#46; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> shows the subjective evaluations of these patients according to their DED etiology &#40;EDE or other types&#41;&#46; There were no statistically significant differences in percentages of patients that reported feeling the same or worse and those who reported feeling better &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;729&#41;&#46; Treatment compliance was significantly correlated with the final subjective evaluation using Pearson&#39;s &#967;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> test &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239; 0&#46;002&#41;&#44; so that 57&#46;41&#37; of compliant patients reported feeling better&#44; compared to 12&#46;50&#37; of non-compliant patients&#46; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows paired differences in endothelial parameters according to corneal staining degree&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0030" class="elsevierStylePara elsevierViewall">SFAs are colorless&#44; physically&#44; chemically and physiologically inert liquids&#44; with substantially reduced densities &#40;between 1&#46;1 and 1&#46;7&#8239;g&#47;cm<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#41; and very low surface tensions&#46; They can be used as medicine solvents or solubilizers&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> According to the current DEWS II report&#44; DED classification includes a wide range of etiologies that can be divided in 2&#8239;subtypes&#58; aqueous-deficient dry eye and EDE&#44; but they often overlap&#46; The classification algorithm and treatment decisions are more favorable to EDE than aqueous-deficient dry eye&#44; since EDE is more common&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> The main cause of this condition is Meibomian glands dysfunction&#44; although there are other anomalies that can cause it&#44; such as mucin deficiency&#44; contact lense use or changes related to blinking&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> The main goal of this study was to evaluate F6H8s safety and efficacy on the ocular surface and corneal endothelium in patients diagnosed with DED of various etiologies&#46; To date&#44; no endothelial safety studies have been conducted in patients treated with topical SFAs&#46; From the 45 patients that started the study&#44; 32 were classified as compliant &#40;71&#46;1&#37;&#41; and 13 as non-compliant &#40;28&#46;9&#37;&#41;&#46; In some cases&#44; this was due to the fact that they were unable to pay for treatment&#46; At the start of the study&#44; the non-compliant group had worse endothelial values in terms of coefficient of variation&#44; HEX&#44; and CCC&#44; and no changes were observed in the average corneal staining level&#44; although this also appeared to be worse&#46; Throughout the study&#44; a statistically significant improvement in corneal staining was observed from M3 which became even more evident in M6&#44; indicating that this compound is effective in treating keratitis caused by DED&#46; However&#44; no statistically significant improvement in conjunctival staining was observed&#46; This may be due to the fact that F6H8 has a different bioadhesive nature in damaged corneal epithelium and damaged conjunctival epithelium&#44; in addition to worse area coverage and slower conjunctival cell recovery&#46; On the other hand&#44; according to previous research&#44;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a> if F6H8 had caused corneal endothelium toxicity&#44; an increase in corneal thickness or some alteration in the endothelium should have been observed as a sign of endothelial dysfunction&#46; The results of this study show that F6H8&#44; regardless of corneal penetration&#44; does not cause toxicity to the corneal endothelium&#44; since there were no significant changes in the variables collected after 6&#8239; months of treatment&#46; Moreover&#44; the beneficial effects on corneal epithelial barrier recovery &#40;shown by corneal staining reduction&#41; appear to cause a significant decrease in patient CCC with a higher degree of corneal staining at D0&#44; in contrast with patients who did not have a high degree of corneal staining&#44; for whom CCC showed no significant changes&#46; This may also indicate the existence of subclinical corneal edema in conditions such as DED&#44; which presents with keratitis and improves when the ocular surface is treated&#46; A less likely&#44; but still possible explanation&#44; is that Evotears&#174; &#40;Brill Pharma SL&#44; Barcelona&#44; Spain&#41; has a positive or protective effect on endothelial function&#44; but further studies would be needed to research this&#46; Furthermore&#44; at the end of the study&#44; 86&#46;48&#37; of patients reported feeling the same &#40;40&#46;54&#37;&#41; or better &#40;45&#46;94&#37;&#41; after treatment&#44; compared to 13&#46;52&#37; who reported feeling worse&#46; Given F6H8s waterproofing capabilities and its ability to retain water&#44; we expect to find differences in ocular surface improvement&#44; satisfaction degree and compliance according to the DED etiology&#44; although it is more effective for EDE&#46; Nevertheless&#44; the treatment improved EDE and other types of DED&#46; However&#44; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> shows a slight trend towards greater subjective improvement &#40;not statistically significant&#41; in patients with EDE&#46; In the present study&#44; all patients diagnosed with EDE presented Meibomian glands dysfunction&#44; so it is possible that the treatment efficacy in this case is due to F6H8s dispersing properties&#44; caused by its low surface tension &#40;19&#46;65&#8239;mN&#47;m&#41;&#44; which stabilizes tear films that lack an optimal lipid layer&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Lipids that obstruct the ducts could potentially be dissolved with F6H8&#44; allowing them to reopen&#46; More studies are needed to test these hypotheses&#46; This study did not differentiate DED types and etiologies&#44; since the focus was on a new generic treatment and its consequences for all symptomatic DED&#44; only distinguishing EDE and others&#46; However&#44; more studies are needed to differentiate the effectiveness of this treatment according to these variables&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Ultimately&#44; in the present study&#44; F6H8s&#8239; efficacy and safety have shown that it is a useful treatment option for patients with DED&#44; since treatment did not change the measured endothelial variables and produced a significant improvement in corneal staining&#44; as well as a decrease in possible subclinical corneal edema due to DED&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflict of interests</span><p id="par0040" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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    "fechaRecibido" => "2020-01-16"
    "fechaAceptado" => "2020-05-19"
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            0 => "EvoTears&#174;"
            1 => "Perfluorohexyloctane"
            2 => "Endothelium"
            3 => "Dry eye disease"
            4 => "Ocular surface"
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          "palabras" => array:5 [
            0 => "Evotears"
            1 => "Perfluorohexiloctano"
            2 => "Endotelio"
            3 => "Enfermedad de ojo seco"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">To evaluate the effects and safety of topical drops of perfluorohexyloctane &#40;F6H8&#41; on the ocular surface and the corneal endothelium&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Forty-five patients &#40;90 eyes&#41; diagnosed with dry eye disease &#40;DED&#41; were recruited and prescribed treatment with F6H8 as part of a six-month prospective multicentre study&#46; Variables in corneal staining were documented using the National Eye Institute&#47;Industry Workshop &#40;NEI&#41; scale&#46; The conjunctival variables included using the Oxford scale&#44; as well as corneal parameters&#44; such as central corneal thickness&#44; cell density&#44; coefficient of variation&#44; hexagonality&#44; and mean cell area&#44; at the start of the study&#44; and at three months and six months&#46; Compliance and satisfaction with the treatment were measured&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">F6H8 drops reduced mean corneal staining based on the NEI scale in compliant patients to a mean of &#8722;0&#46;84&#8239;&#177;&#8239;1&#46;95 at three months &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;001&#41; and to &#8722;1&#46;65 &#177; 2&#46;42 at six months &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;&#46;001&#41;&#46; Conjunctival staining at six months showed a mean decrease of &#8722;0&#46;13 &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;319&#41;&#46; The endothelial parameters did not show a significant difference&#44; in contrast to the central corneal thickness that showed a statistically significant decrease &#40;545&#46;30 &#177; 32&#46;25 at the start of the study to 538&#46;40 &#177; 31&#46;36 after six months&#44; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;009&#41;&#46; At the end of the study&#44; 46&#37; of patients reported feeling subjectively better&#44; 40&#46;5&#37; felt the same&#44; and 13&#46;5&#37; felt subjectively worse&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Topical treatment with F6H8 for DED did not alter the measured variables of the corneal endothelium&#44; but showed improvement in corneal staining and satisfaction&#46;</p></span>"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Evaluar los efectos y la seguridad del perfluorohexiloctano &#40;F6H8&#41; t&#243;pico en la superficie ocular y el endotelio corneal&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Cuarenta y cinco pacientes &#40;90 ojos&#41; diagnosticados de Enfermedad de Ojo Seco &#40;EOS&#41; fueron reclutados y se les prescribi&#243; tratamiento con F6H8 durante seis meses&#46; Las variables en la tinci&#243;n corneal se documentaron usando la escala <span class="elsevierStyleItalic">National Eye Institute&#47;Industry Workshop</span> &#40;NEI&#41;&#44; las variables conjuntivales usando la escala Oxford&#44; y los par&#225;metros corneales como el espesor corneal central&#44; la densidad celular&#44; el coeficiente de variaci&#243;n&#44; la hexagonalidad y el &#225;rea celular promedio&#44; al inicio del estudio&#44; a los tres meses y a los seis meses&#46; Se evalu&#243; tambi&#233;n el cumplimiento y la satisfacci&#243;n&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">el tratamiento con F6H8 redujo la tinci&#243;n corneal promedio en pacientes cumplidores a una media de -0&#44;84&#8239;&#177;&#8239;1&#44;95 a los tres meses &#40;p&#8239;&#61;&#8239;0&#44;001&#41; y a -1&#44;65&#8239;&#177;&#8239;2&#44;42 a los seis meses &#40;p&#8239;&#60;&#8239;0&#44;001&#41;&#46; La tinci&#243;n conjuntival a los seis meses mostr&#243; una disminuci&#243;n promedio de -0&#44;13 &#40;p&#8239;&#61;&#8239;0&#44;319&#41;&#46; Los par&#225;metros endoteliales no mostraron diferencia significativa&#44; excepto el espesor corneal central que mostr&#243; una disminuci&#243;n estad&#237;sticamente significativa &#40;545&#44;30&#8239;&#177;&#8239;32&#44;25&#956;m al comienzo del estudio y 538&#44;40&#8239;&#177;&#8239;31&#44;36&#956;m tras seis meses&#44; p&#8239;&#61;&#8239;0&#44;009&#41;&#46; Al final del estudio&#44; el 46&#37; de los pacientes informaron sentirse subjetivamente mejor&#44; el 40&#44;5&#37; no sinti&#243; cambios y el 13&#44;5&#37; se sinti&#243; subjetivamente peor&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">El tratamiento t&#243;pico con F6H8 para EOS no alter&#243; las variables medidas del endotelio corneal&#44; mostrando mejor&#237;a en la tinci&#243;n corneal y en la satisfacci&#243;n&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
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          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
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          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
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      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Mateo Orobia AJ&#44; Blasco-Martinez A&#44; Rodr&#237;guez-Aus&#237;n P&#44; Pablo J&#250;lvez LE&#44; G&#252;emes Villahoz N&#44; del Prado Sanz E&#44; et al&#46; Efectos y seguridad del perfluorohexiloctano en la superficie ocular y el endotelio corneal&#46; Arch Soc Esp Oftalmol&#46; 2020&#59;95&#58;538&#8211;543&#46;</p>"
      ]
    ]
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      0 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1248
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Paired differences in corneal staining&#46; M3&#58; month 3&#59; M6&#58; month 6&#46;</p>"
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      1 => array:8 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0010"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Subjective evaluations&#46; DED&#58; dry eye disease&#59; EDE&#58; evaporative dry eye&#46;</p>"
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      ]
      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Asterisks mark statistically significant differences&#46; AVG&#58; average cell area&#59; CV&#58; coefficient of variation&#59; CD&#58; endothelial cell density&#59; SD&#58; standard deviation&#59; CCC&#44; central corneal thickness&#59; HEX&#58; percentage of cellular hexagonality&#59; NEI&#58; National Eye Institute &#40;scale used for corneal staining with fluorescein&#41;&#59; LG&#58; lysamine green &#40;Oxford scale used for corneal&#47;conjunctival staining&#41;&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Average&#8239;&#177;&#8239;SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Confidence interval of 95&#37;</th><th class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Lower limit&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Upper limit&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NEI &#40;0&#8722;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complying&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;79&#8239;&#177;&#8239;3&#46;87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;222&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non complying&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;69&#8239;&#177;&#8239;4&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;81&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LG &#40;0&#8722;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complying&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;34&#8239;&#177;&#8239;1&#46;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;708&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non complying&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;79&#8239;&#177;&#8239;3&#46;87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CD &#40;cells&#47;mm<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complying&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2296&#46;68&#8239;&#177;&#8239;521&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2157&#46;43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2428&#46;48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;710&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non complying&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2456&#46;75&#8239;&#177;&#8239;511&#46;86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2220&#46;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2722&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CV &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complying&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#46;98&#8239;&#177;&#8239;6&#46;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#46;38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;024&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non complying&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#46;13&#8239;&#177;&#8239;5&#46;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#46;77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&#46;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HEX &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complying&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#46;77&#8239;&#177;&#8239;17&#46;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 0&#46;001&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non complying&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&#46;88&#8239;&#177;&#8239;17&#46;70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#46;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AVG &#40;&#956;m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complying&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">466&#46;17&#8239;&#177;&#8239;139&#46;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">431&#46;49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">503&#46;49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;664&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non complying&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">425&#46;06&#8239;&#177;&#8239;93&#46;34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">377&#46;40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">470&#46;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCC &#40;&#956;m&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complying&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">545&#46;85&#8239;&#177;&#8239;40&#46;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">534&#46;54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">556&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;010&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non complying&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">512&#46;13&#8239;&#177;&#8239;30&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">497&#46;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">527&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2413030.png"
              ]
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Descriptive data and average comparison between complying and non-complying patients with staining and endothelial parameters&#46;</p>"
        ]
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      3 => array:8 [
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        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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          0 => array:3 [
            "identificador" => "at0020"
            "detalle" => "Table "
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">AVG&#58; average cell area&#59; CV&#58; coefficient of variation&#59; D0&#58; day 0&#59; CD&#58; endothelial cell density&#59; SD&#58; standard deviation&#59; CCC&#44; central corneal thickness&#59; HEX&#58; percentage of cellular hexagonality&#59; M6&#58; month 6&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Average difference&#8239;&#177;&#8239;SD&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CV D0 vs&#46; M6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;287&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HEX D0 vs&#46; M6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AVG D0 vs&#46; M6&nbsp;\t\t\t\t\t\t\n
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