Switching prostaglandin analogs and 24-h IOP fluctuations | Archivos de la Sociedad Española de Oftalmología (English Edition)

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La brinzolamida tiene una PIO promedio significativamente mayor en todas las horas." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "F. Gil-Carrasco, M. Turati-Acosta, O. Albis-Donado, H. Bello-López-Portillo, C. Sánchez-Noguera, K. Soto-Ortiz" "autores" => array:6 [ 0 => array:2 [ "nombre" => "F." "apellidos" => "Gil-Carrasco" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Turati-Acosta" ] 2 => array:2 [ "nombre" => "O." "apellidos" => "Albis-Donado" ] 3 => array:2 [ "nombre" => "H." "apellidos" => "Bello-López-Portillo" ] 4 => array:2 [ "nombre" => "C." "apellidos" => "Sánchez-Noguera" ] 5 => array:2 [ "nombre" => "K." 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Gil-Carrasco, M. Turati-Acosta, O. Albis-Donado, H. Bello-López-Portillo, C. Sánchez-Noguera, K. Soto-Ortiz" "autores" => array:6 [ 0 => array:4 [ "nombre" => "F." "apellidos" => "Gil-Carrasco" "email" => array:1 [ 0 => "fegica@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "¿" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Turati-Acosta" ] 2 => array:2 [ "nombre" => "O." "apellidos" => "Albis-Donado" ] 3 => array:2 [ "nombre" => "H." "apellidos" => "Bello-López-Portillo" ] 4 => array:2 [ "nombre" => "C." "apellidos" => "Sánchez-Noguera" ] 5 => array:2 [ "nombre" => "K." "apellidos" => "Soto-Ortiz" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Departamento de Glaucoma, Asociación para evitar la ceguera en México, Hospital Dr. Luis Sánchez Bulnes, México City, Mexico" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Rotación de análogos de prostaglandinas y fluctuaciones diurnas de la presión intraocular" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1096 "Ancho" => 1704 "Tamanyo" => 111792 ] ] "descripcion" => array:1 [ "en" => "Mean IOP graph with each drug in each measurement time. Brinzolamide exhibits a significantly higher mean IOP in all measurement times." ] ] ] "textoCompleto" => "IntroductionProstaglandin-derived hypotensor lipids are the most powerful ocular hypotensor agents available as monotherapy. Latanoprost 0.005% and travoprost 0.004% are pro-drugs and require corneal stearases to obtain the active metabolite. Bimatoprost 0.03% also undergoes corneal metabolism but is partially absorbed without metabolizing, achieving anterior chamber concentrations higher than those obtained by travoprost from its metabolite and detectable from the original molecule.<a class="elsevierStyleCrossRefs" href="#bib0005">1,2</a> Said 3 medications reduce intraocular pressure (IOP) enhancing exit through nonconventional or uveoscleral pathway, associated to enlargement of spaces between ciliary muscle fibers and remodeling the extracellular matrix. In addition, bimatoprost seems to have an additional effect over the conventional or trabecular pathway,<a class="elsevierStyleCrossRef" href="#bib0015">3</a> and appears to be more effective in reducing IOP when compared to latanoprost.<a class="elsevierStyleCrossRef" href="#bib0020">4</a>Said drugs have demonstrated superiority compared with timolol, brimonidine and dorzolamide in several clinical trials. Their effectiveness has taken them to the first line of treatment for patients with ocular hypertension and open angle glaucoma.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> It has been proposed that some patients in treatment with a prostaglandin analog and who require additional IOP reductions can exhibit it when switching to a different analog, particularly patients exhibiting poor or no response to latanoprost.<a class="elsevierStyleCrossRef" href="#bib0030">6</a>Several researchers have considered IOP variations as an important risk factor for the progression of glaucoma.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> This study aims at establishing whether the effect of the different hypotensor lipids over nocturnal IOP oscillations is similar or changes when switching from one therapy to another.Subject, materials and methodsMexican mestizo patients with open angle primary glaucoma were selected, having slight/moderate degree in the visual field with a mean deviation of 9dB or less without central defects and without having used antiglaucoma medication in the past. The mean age of the 11 females and 3 males was of 58.3 years. The mean IOP before beginning the study was of 22.1mmHg (DS 2.6mmHg, range 18–29mmHg). The patients were recruited for the study in 3 different stages. In the first, 7 patients were included, one eye for each. In the second and third stages the 2 eyes of 7 additional patients were included. IOP curves with Perkins applanation tonometer were taken (Perkins hand applanation tonometer, Haag-Streit, Harlow, Essex, United Kingdom), taking measurements at 09:00, 13:00, 17:00, 21:00, 23:00, 01:00, 05:00 and 06:00h. The early morning measurements were taken with patients lying on their back.Every month the treatment switched between brinzolamide (Azopt, Alcon Labs, Fort Worth, USA), latanoprost (Xalatan, Pfizer, NY, USA), travoprost (Travatan, Alcon, Fort Worth, USA) and bimatoprost (Lumigan, Allergan, Irvine, USA), switching the order between analogs and alternating with brinzolamide (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Measured parameters included the average pressure of each curve, variations (the difference between an maximum IOP of each curve), the effect of the treatment order, the mean pressures of the curve at each time of the day and the effects of each medication on pressures and fluctuations. The mean values were analyzed with ANOVA and multivariate linear models were constructed with generalized estimation equations to determine the effect of repeated measurements and subjects. The data were analyzed with SPSS for Windows, version 16 (IBM SPSS Statistics, IBM Corporation Software Group, Somers, NY, USA), and the analysis was repeated including a single eye of each subject. The study was approved by the Ethical Committee of our institution and each participant signed an informed consent before beginning the follow-up.ResultsFour hundred hourly curves were scheduled and overall 393 were carried out, 157 with brinzolamide, 80 with bimatoprost, 79 with travoprost and 77 with latanoprost. Each patient had between 10 and 50 curves depending on the number of years in the follow-up and the number of eyes considered for the study. When both eyes were included, 2 curves were counted. Overall, 7 patients had 10 curves, 4 with brinzolamida and 2 with each analog, using only one eye of these patients. In addition, 5 patients had 50 curves, 20 with azopt and 10 with each analog, using both eyes of these patients. The other 2 patients had 40 curves for both eyes, 16 with azopt and 8 with each analog. Overall, the study required a period of 3 years with two-month intervals at the end of each ten-month stage for completion.The IOP and variation mean values during the curves were significantly higher between brinzolamide and any of the 3 analogs (p<0.001; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>The mean IOP in each hour of the day was higher with brinzolamide compared with any of the analogs, said difference being significant (p<0.002; <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Excluding the curves with brinzolamide, the differences between the 3 analogs were very small at all times, with the biggest difference occurring at 06:00, where bimatoprost achieved a mean IOP of 14.4mmHg, in comparison with 15.7mmHg for travoprost and 15.8mmHg for latanoprost (nonsignificant difference, p=0.121; <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> and <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>The results of the multivariate analysis with the 4 drugs were similar, with brinzolamide being identified as having the highest fluctuations and mean IOP. In addition, it was useful to verify the correct identification of each curve with the adequate patient. When the multivariate analysis was repeated excluding brinzolamide, a lower variation of 0.49mmHg with bimatoprost was found (CI: 95; −0.87 to −0.10, p=0.013) when compared with latanoprost. The variation was 0.30mmHg higher with travoprost, without being statistically significant (CI: 95; −0.15 to 0.74, p=0.195). The order of analog rotation was not found to affect the results on the mean pressure obtained during the curve or over the fluctuations thereof.DiscussionBrinzolamide turned out to be less effective than analogs for reducing the mean IOP and its oscillations over the 24h. This effect seems even lower in the early morning. On the other hand, hypotensor lipids performed better, diminishing the mean IOP and its oscillations over 24h, with a slight advantage of bimatoprost at 6am and in the multivariate isolation analysis which was not considered clinically significant in our small group of patients.Even though an additional response has been described in patients who do not respond to latanoprost with the use of bimatoprost or travoprost,<a class="elsevierStyleCrossRefs" href="#bib0030">6,8</a> in this group of patients no significant changes were identified when switching from one analog to the other. It is possible that this switch is a good strategy in patients requiring additional IOP reduction although that improved response will not always occur. If the response to the analog is good, additional reductions may not be produced.The effect of each analog on IOP oscillations and glaucoma progression is a worthwhile subject for in-depth study with a larger group of patients.Conflict of interestsNo conflict of interest has been declared by the authors." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xres190819" "titulo" => array:5 [ 0 => "Abstract" 1 => "Objectives" 2 => "Methods" 3 => "Results" 4 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec178281" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres190818" "titulo" => array:5 [ 0 => "Resumen" 1 => "Objetivos" 2 => "Métodos" 3 => "Resultados" 4 => "Conclusiones" ] ] 3 => array:2 [ "identificador" => "xpalclavsec178282" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Subject, materials and 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" => "2011-06-22" "fechaAceptado" => "2012-06-22" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec178281" "palabras" => array:7 [ 0 => "Glaucoma" 1 => "Prostaglandin analogs" 2 => "Intraocular pressure" 3 => "Brinzolamide" 4 => "Latanoprost" 5 => "Travoprost" 6 => "Bimatoprost" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec178282" "palabras" => array:7 [ 0 => "Glaucoma" 1 => "Análogos de prostaglandinas" 2 => "Presión intraocular" 3 => "Brinzolamida" 4 => "Latanoprost" 5 => "Travoprost" 6 => "Bimatoprost" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "ObjectivesTo evaluate the fluctuations in 24h mean intraocular pressure (IOP) when switching prostaglandin analogs in patients with glaucoma. MethodsFourteen patients with primary open angle glaucoma were evaluated with monthly 24-h IOP curves, using a monthly switching pattern of prostaglandin analogs and brinzolamide during 3 years of follow-up. ResultsAverage IOP and average fluctuation (peak to through difference) were significantly higher with brinzolamide than with any of the analogs. There was no significant difference in either parameter with the different prostaglandin analogs, regardless of the order in which they were evaluated, or even if a month on brinzolamide was intercalated between the analogs. ConclusionsBrinzolamide was less effective than prostaglandin analogs in reducing 24-h mean IOP and its fluctuations. Switching analogs had no significant effect on mean IOP or mean IOP fluctuations." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "ObjetivosEvaluar la eficacia de la rotación de análogos de prostaglandinas sobre las fluctuaciones de la presión intraocular (PIO) en 24h. MétodosSe evaluó a 14 pacientes con glaucoma primario de ángulo abierto mediante curvas mensuales de presión intraocular de 24h, realizando un patrón de cambios mensuales del tratamiento hipotensor entre brinzolamida y análogos de prostaglandinas durante un período de tres años. ResultadosTanto el promedio de PIO como el promedio de variación (diferencia entre el pico y el valle) durante las curvas fueron significativamente mayores con la brinzolamida que con cualquiera de los tres análogos. Tanto el promedio de PIO como el promedio de fluctuaciones fueron similares entre los tres análogos, independiente del orden en que se usaron o de si se intercaló un mes de brinzolamida entre uno y otro análogo. ConclusionesLa brinzolamida fue menos efectiva para reducir la PIO promedio y sus fluctuaciones durante 24h. No hubo un cambio significativo al rotar los análogos." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Gil-Carrasco F, et al. Rotación de análogos de prostaglandinas y fluctuaciones diurnas de la presión intraocular. Arch Soc Esp Oftalmol. 2013;88:130–3." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1096 "Ancho" => 1704 "Tamanyo" => 111792 ] ] "descripcion" => array:1 [ "en" => "Mean IOP graph with each drug in each measurement time. Brinzolamide exhibits a significantly higher mean IOP in all measurement times." ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Az, brinzolamide; B, bimatoprost; L, latanoprost; T, travoprost." "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"><td 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" style="border-bottom: 2px solid black">Mes stage \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">10 \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \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">Az \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">L \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">Az \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">B \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">Az \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\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">Az \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">L \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">B \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\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \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">Az \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">B \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">Az \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\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">Az \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">L \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">Az \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">B \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\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">L \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \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">Az \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\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">Az \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">L \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">Az \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">B \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">Az \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\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">L \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">B \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab326360.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Order of treatment for each stage." ] ] 2 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "The differences between brinzolamide and each analog are significant (except for the lowest IOP) but not between the analogs.SD, standard deviation." "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"><td 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" style="border-bottom: 2px solid black">Drug \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Mean IOP mmHg (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Lowest mean IOP mmHg (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Highest mean IOP mmHg (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Mean IOP variation mmHg (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">No. \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">Brinzolamide \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16.26 (3.55) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.15 (3.27) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19.54 (3.99) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.39 (2.42) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">157 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Bimatoprost \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.16 (3.33) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.14 (2.86) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16.40 (4.00) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.26 (1.79) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">80 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Travoprost \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.55 (3.41) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.35 (3.05) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16.75 (3.85) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.39 (1.86) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Latanoprost \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.41 (3.64) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.31 (3.09) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17.01 (4.57) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.70 (2.79) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">77 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">p \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="char" 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><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.053 \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="char" 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><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" 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><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" 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 => "xTab326359.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Intraocular pressure average values, highest, lowest and isolation average during the curves with each drug." ] ] 3 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Brinzolamide exhibits significantly higher IOP values in all measurements.SD, standard deviation." "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"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" 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-head\n \t\t\t\t " colspan="8" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Mean IOP mmHg (SD)</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">9:00h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">13:00h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">15:00h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">21:00h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">23:00h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">01:00h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">05:00h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">06:00h \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">Brinzolamide \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.89 (4.49) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.46 (4.07) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16.12 (3.71) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16.04 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16.11 (3.88) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16.63 (4.13) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18.04 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17.97 (4.24) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Bimatoprost \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.09 (3.24) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.35 (3.43) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.13 (3.14) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.18 (3.61) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.29 (3.70) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.68 (3.66) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.49 (4.35) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.38 (4.04) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Travoprost \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.73 (3.50) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.35 (3.75) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.06 (3.56) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.72 (3.42) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.24 (3.83) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.90 (4.24) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.49 (3.84) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.71 (3.45) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Latanoprost \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.26 (3.78) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.51 (3.52) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.62 (3.50) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.51 (4.06) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.35 (3.95) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.34 (4.64) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.91 (4.20) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.84 (4.26) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab326361.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Mean intraocular pressure at different times of the day and standard deviations." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hydrolysis of bimatoprost (Lumigan) to its free acid by ocular tissue in vitro" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S.S. Davies" 1 => "W.K. Ju" 2 => "A.H. Neufeld" 3 => "D. Abran" 4 => "S. Chemtob" 5 => "L.J. Roberts" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1089/108076803762718105" "Revista" => array:6 [ "tituloSerie" => "J Ocul Pharmacol Ther" "fecha" => "2003" "volumen" => "19" "paginaInicial" => "45" "paginaFinal" => "54" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12648303" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Aqueous humor concentrations of bimatoprost free acid, bimatoprost and travoprost free acid in cataract surgical patients administered multiple topical ocular doses of Lumigan or Travatan" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Faulkner" 1 => "N.A. Sharif" 2 => "S. Orr" 3 => "K. Sall" 4 => "H. Dubiner" 5 => "J.T. 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Kaufman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.survophthal.2008.08.010" "Revista" => array:7 [ "tituloSerie" => "Surv Ophthalmol" "fecha" => "2008" "volumen" => "53" "numero" => "Suppl. 1" "paginaInicial" => "S107" "paginaFinal" => "S120" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19038618" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical utility and differential effects of prostaglandin analogs in the management of raised intraocular pressure and ocular hypertension" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.J. Lee" 1 => "P. McCluskey" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Ophthalmol" "fecha" => "2010" "volumen" => "4" "paginaInicial" => "741" "paginaFinal" => "764" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20689791" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment principles and options" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "European Glaucoma Society" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:5 [ "edicion" => "3rd ed." "titulo" => "EGS terminology and guidelines" "fecha" => "2008" "editorial" => "Editrice Dogma S.R.L." 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Switching prostaglandin analogs and 24-h IOP fluctuations

Rotación de análogos de prostaglandinas y fluctuaciones diurnas de la presión intraocular

F. Gil-Carrasco

Corresponding author

fegica@hotmail.com

Corresponding author.

, M. Turati-Acosta, O. Albis-Donado, H. Bello-López-Portillo, C. Sánchez-Noguera, K. Soto-Ortiz

Departamento de Glaucoma, Asociación para evitar la ceguera en México, Hospital Dr. Luis Sánchez Bulnes, México City, Mexico

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Prostaglandin-derived hypotensor lipids are the most powerful ocular hypotensor agents available as monotherapy&#46; Latanoprost 0&#46;005&#37; and travoprost 0&#46;004&#37; are pro-drugs and require corneal stearases to obtain the active metabolite&#46; Bimatoprost 0&#46;03&#37; also undergoes corneal metabolism but is partially absorbed without metabolizing&#44; achieving anterior chamber concentrations higher than those obtained by travoprost from its metabolite and detectable from the original molecule&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> Said 3 medications reduce intraocular pressure &#40;IOP&#41; enhancing exit through nonconventional or uveoscleral pathway&#44; associated to enlargement of spaces between ciliary muscle fibers and remodeling the extracellular matrix&#46; In addition&#44; bimatoprost seems to have an additional effect over the conventional or trabecular pathway&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and appears to be more effective in reducing IOP when compared to latanoprost&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Said drugs have demonstrated superiority compared with timolol&#44; brimonidine and dorzolamide in several clinical trials&#46; Their effectiveness has taken them to the first line of treatment for patients with ocular hypertension and open angle glaucoma&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> It has been proposed that some patients in treatment with a prostaglandin analog and who require additional IOP reductions can exhibit it when switching to a different analog&#44; particularly patients exhibiting poor or no response to latanoprost&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Several researchers have considered IOP variations as an important risk factor for the progression of glaucoma&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> This study aims at establishing whether the effect of the different hypotensor lipids over nocturnal IOP oscillations is similar or changes when switching from one therapy to another&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Subject&#44; materials and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">Mexican <span class="elsevierStyleItalic">mestizo</span> patients with open angle primary glaucoma were selected&#44; having slight&#47;moderate degree in the visual field with a mean deviation of 9<span class="elsevierStyleHsp" style=""></span>dB or less without central defects and without having used antiglaucoma medication in the past&#46; The mean age of the 11 females and 3 males was of 58&#46;3 years&#46; The mean IOP before beginning the study was of 22&#46;1<span class="elsevierStyleHsp" style=""></span>mmHg &#40;DS 2&#46;6<span class="elsevierStyleHsp" style=""></span>mmHg&#44; range 18&#8211;29<span class="elsevierStyleHsp" style=""></span>mmHg&#41;&#46; The patients were recruited for the study in 3 different stages&#46; In the first&#44; 7 patients were included&#44; one eye for each&#46; In the second and third stages the 2 eyes of 7 additional patients were included&#46; IOP curves with Perkins applanation tonometer were taken &#40;Perkins hand applanation tonometer&#44; Haag-Streit&#44; Harlow&#44; Essex&#44; United Kingdom&#41;&#44; taking measurements at 09&#58;00&#44; 13&#58;00&#44; 17&#58;00&#44; 21&#58;00&#44; 23&#58;00&#44; 01&#58;00&#44; 05&#58;00 and 06&#58;00<span class="elsevierStyleHsp" style=""></span>h&#46; The early morning measurements were taken with patients lying on their back&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Every month the treatment switched between brinzolamide &#40;Azopt&#44; Alcon Labs&#44; Fort Worth&#44; USA&#41;&#44; latanoprost &#40;Xalatan&#44; Pfizer&#44; NY&#44; USA&#41;&#44; travoprost &#40;Travatan&#44; Alcon&#44; Fort Worth&#44; USA&#41; and bimatoprost &#40;Lumigan&#44; Allergan&#44; Irvine&#44; USA&#41;&#44; switching the order between analogs and alternating with brinzolamide &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Measured parameters included the average pressure of each curve&#44; variations &#40;the difference between an maximum IOP of each curve&#41;&#44; the effect of the treatment order&#44; the mean pressures of the curve at each time of the day and the effects of each medication on pressures and fluctuations&#46; The mean values were analyzed with ANOVA and multivariate linear models were constructed with generalized estimation equations to determine the effect of repeated measurements and subjects&#46; The data were analyzed with SPSS for Windows&#44; version 16 &#40;IBM SPSS Statistics&#44; IBM Corporation Software Group&#44; Somers&#44; NY&#44; USA&#41;&#44; and the analysis was repeated including a single eye of each subject&#46; The study was approved by the Ethical Committee of our institution and each participant signed an informed consent before beginning the follow-up&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0035" class="elsevierStylePara elsevierViewall">Four hundred hourly curves were scheduled and overall 393 were carried out&#44; 157 with brinzolamide&#44; 80 with bimatoprost&#44; 79 with travoprost and 77 with latanoprost&#46; Each patient had between 10 and 50 curves depending on the number of years in the follow-up and the number of eyes considered for the study&#46; When both eyes were included&#44; 2 curves were counted&#46; Overall&#44; 7 patients had 10 curves&#44; 4 with brinzolamida and 2 with each analog&#44; using only one eye of these patients&#46; In addition&#44; 5 patients had 50 curves&#44; 20 with azopt and 10 with each analog&#44; using both eyes of these patients&#46; The other 2 patients had 40 curves for both eyes&#44; 16 with azopt and 8 with each analog&#46; Overall&#44; the study required a period of 3 years with two-month intervals at the end of each ten-month stage for completion&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The IOP and variation mean values during the curves were significantly higher between brinzolamide and any of the 3 analogs &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#59; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">The mean IOP in each hour of the day was higher with brinzolamide compared with any of the analogs&#44; said difference being significant &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#59; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Excluding the curves with brinzolamide&#44; the differences between the 3 analogs were very small at all times&#44; with the biggest difference occurring at 06&#58;00&#44; where bimatoprost achieved a mean IOP of 14&#46;4<span class="elsevierStyleHsp" style=""></span>mmHg&#44; in comparison with 15&#46;7<span class="elsevierStyleHsp" style=""></span>mmHg for travoprost and 15&#46;8<span class="elsevierStyleHsp" style=""></span>mmHg for latanoprost &#40;nonsignificant difference&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;121&#59; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> and <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">The results of the multivariate analysis with the 4 drugs were similar&#44; with brinzolamide being identified as having the highest fluctuations and mean IOP&#46; In addition&#44; it was useful to verify the correct identification of each curve with the adequate patient&#46; When the multivariate analysis was repeated excluding brinzolamide&#44; a lower variation of 0&#46;49<span class="elsevierStyleHsp" style=""></span>mmHg with bimatoprost was found &#40;CI&#58; 95&#59; &#8722;0&#46;87 to &#8722;0&#46;10&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;013&#41; when compared with latanoprost&#46; The variation was 0&#46;30<span class="elsevierStyleHsp" style=""></span>mmHg higher with travoprost&#44; without being statistically significant &#40;CI&#58; 95&#59; &#8722;0&#46;15 to 0&#46;74&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;195&#41;&#46; The order of analog rotation was not found to affect the results on the mean pressure obtained during the curve or over the fluctuations thereof&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0055" class="elsevierStylePara elsevierViewall">Brinzolamide turned out to be less effective than analogs for reducing the mean IOP and its oscillations over the 24<span class="elsevierStyleHsp" style=""></span>h&#46; This effect seems even lower in the early morning&#46; On the other hand&#44; hypotensor lipids performed better&#44; diminishing the mean IOP and its oscillations over 24<span class="elsevierStyleHsp" style=""></span>h&#44; with a slight advantage of bimatoprost at 6<span class="elsevierStyleHsp" style=""></span>am and in the multivariate isolation analysis which was not considered clinically significant in our small group of patients&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Even though an additional response has been described in patients who do not respond to latanoprost with the use of bimatoprost or travoprost&#44;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;8</span></a> in this group of patients no significant changes were identified when switching from one analog to the other&#46; It is possible that this switch is a good strategy in patients requiring additional IOP reduction although that improved response will not always occur&#46; If the response to the analog is good&#44; additional reductions may not be produced&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The effect of each analog on IOP oscillations and glaucoma progression is a worthwhile subject for in-depth study with a larger group of patients&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interests</span><p id="par0070" class="elsevierStylePara elsevierViewall">No conflict of interest has been declared by the authors&#46;</p></span></span>"
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          "identificador" => "xres190819"
          "titulo" => array:5 [
            0 => "Abstract"
            1 => "Objectives"
            2 => "Methods"
            3 => "Results"
            4 => "Conclusions"
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        1 => array:2 [
          "identificador" => "xpalclavsec178281"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "xres190818"
          "titulo" => array:5 [
            0 => "Resumen"
            1 => "Objetivos"
            2 => "M&#233;todos"
            3 => "Resultados"
            4 => "Conclusiones"
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec178282"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Subject&#44; materials and 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" => "2011-06-22"
    "fechaAceptado" => "2012-06-22"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec178281"
          "palabras" => array:7 [
            0 => "Glaucoma"
            1 => "Prostaglandin analogs"
            2 => "Intraocular pressure"
            3 => "Brinzolamide"
            4 => "Latanoprost"
            5 => "Travoprost"
            6 => "Bimatoprost"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec178282"
          "palabras" => array:7 [
            0 => "Glaucoma"
            1 => "An&#225;logos de prostaglandinas"
            2 => "Presi&#243;n intraocular"
            3 => "Brinzolamida"
            4 => "Latanoprost"
            5 => "Travoprost"
            6 => "Bimatoprost"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To evaluate the fluctuations in 24<span class="elsevierStyleHsp" style=""></span>h mean intraocular pressure &#40;IOP&#41; when switching prostaglandin analogs in patients with glaucoma&#46;</p> <span class="elsevierStyleSectionTitle">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Fourteen patients with primary open angle glaucoma were evaluated with monthly 24-h IOP curves&#44; using a monthly switching pattern of prostaglandin analogs and brinzolamide during 3 years of follow-up&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Average IOP and average fluctuation &#40;peak to through difference&#41; were significantly higher with brinzolamide than with any of the analogs&#46; There was no significant difference in either parameter with the different prostaglandin analogs&#44; regardless of the order in which they were evaluated&#44; or even if a month on brinzolamide was intercalated between the analogs&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Brinzolamide was less effective than prostaglandin analogs in reducing 24-h mean IOP and its fluctuations&#46; Switching analogs had no significant effect on mean IOP or mean IOP fluctuations&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Evaluar la eficacia de la rotaci&#243;n de an&#225;logos de prostaglandinas sobre las fluctuaciones de la presi&#243;n intraocular &#40;PIO&#41; en 24<span class="elsevierStyleHsp" style=""></span>h&#46;</p> <span class="elsevierStyleSectionTitle">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se evalu&#243; a 14 pacientes con glaucoma primario de &#225;ngulo abierto mediante curvas mensuales de presi&#243;n intraocular de 24<span class="elsevierStyleHsp" style=""></span>h&#44; realizando un patr&#243;n de cambios mensuales del tratamiento hipotensor entre brinzolamida y an&#225;logos de prostaglandinas durante un per&#237;odo de tres a&#241;os&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Tanto el promedio de PIO como el promedio de variaci&#243;n &#40;diferencia entre el pico y el valle&#41; durante las curvas fueron significativamente mayores con la brinzolamida que con cualquiera de los tres an&#225;logos&#46; Tanto el promedio de PIO como el promedio de fluctuaciones fueron similares entre los tres an&#225;logos&#44; independiente del orden en que se usaron o de si se intercal&#243; un mes de brinzolamida entre uno y otro an&#225;logo&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La brinzolamida fue menos efectiva para reducir la PIO promedio y sus fluctuaciones durante 24<span class="elsevierStyleHsp" style=""></span>h&#46; No hubo un cambio significativo al rotar los an&#225;logos&#46;</p>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara">Please cite this article as&#58; Gil-Carrasco F&#44; et al&#46; Rotaci&#243;n de an&#225;logos de prostaglandinas y fluctuaciones diurnas de la presi&#243;n intraocular&#46; Arch Soc Esp Oftalmol&#46; 2013&#59;88&#58;130&#8211;3&#46;</p>"
      ]
    ]
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      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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        "figura" => array:1 [
          0 => array:4 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Mean IOP graph with each drug in each measurement time&#46; Brinzolamide exhibits a significantly higher mean IOP in all measurement times&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Az&#44; brinzolamide&#59; B&#44; bimatoprost&#59; L&#44; latanoprost&#59; T&#44; travoprost&#46;</p>"
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&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">Az&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">B&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">Az&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">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">Az&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">L&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">Az&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">B&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">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">L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&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">Az&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">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">Az&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">L&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">Az&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">B&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">Az&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">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">L&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">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab326360.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Order of treatment for each stage&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">The differences between brinzolamide and each analog are significant &#40;except for the lowest IOP&#41; but not between the analogs&#46;</p><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">SD&#44; standard deviation&#46;</p>"
          "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"><td 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" style="border-bottom: 2px solid black">Drug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Mean IOP mmHg &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Lowest mean IOP mmHg &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Highest mean IOP mmHg &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Mean IOP variation mmHg &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">No&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">Brinzolamide&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#46;26 &#40;3&#46;55&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46;15 &#40;3&#46;27&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&#46;54 &#40;3&#46;99&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;39 &#40;2&#46;42&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">157&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">Bimatoprost&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;16 &#40;3&#46;33&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#46;14 &#40;2&#46;86&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#46;40 &#40;4&#46;00&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;26 &#40;1&#46;79&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">Travoprost&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;55 &#40;3&#46;41&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#46;35 &#40;3&#46;05&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#46;75 &#40;3&#46;85&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;39 &#40;1&#46;86&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">Latanoprost&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;41 &#40;3&#46;64&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#46;31 &#40;3&#46;09&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#46;01 &#40;4&#46;57&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;70 &#40;2&#46;79&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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"><span class="elsevierStyleItalic">p</span>&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;053&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&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="" 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 => "xTab326359.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Intraocular pressure average values&#44; highest&#44; lowest and isolation average during the curves with each drug&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Brinzolamide exhibits significantly higher IOP values in all measurements&#46;</p><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">SD&#44; standard deviation&#46;</p>"
          "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"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" 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-head\n
                  \t\t\t\t  " colspan="8" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Mean IOP mmHg &#40;SD&#41;</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">9&#58;00<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">13&#58;00<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">15&#58;00<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">Bimatoprost&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Travoprost&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Mean intraocular pressure at different times of the day and standard deviations&#46;</p>"
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                            4 => "H&#46; Dubiner"
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Article information

ISSN: 21735794
Original language: English

DOI:10.1016/j.oftale.2012.06.010

The statistics are updated each day

Year/Month	Html	Pdf	Total

2023 March	1	0	1
2018 March	0	1	1
2018 February	10	1	11
2018 January	10	0	10
2017 December	13	1	14
2017 November	23	0	23
2017 October	21	2	23
2017 September	12	2	14
2017 August	15	0	15
2017 July	19	3	22
2017 June	29	16	45
2017 May	30	2	32
2017 April	17	2	19
2017 March	30	4	34
2017 February	28	2	30
2017 January	19	1	20
2016 December	31	7	38
2016 November	42	7	49
2016 October	44	5	49
2016 September	31	9	40
2016 August	27	2	29
2016 July	26	2	28
2016 June	29	15	44
2016 May	22	17	39
2016 April	21	9	30
2016 March	22	19	41
2016 February	23	16	39
2016 January	18	18	36
2015 December	32	11	43
2015 November	17	15	32
2015 October	23	17	40
2015 September	26	4	30
2015 August	22	7	29
2015 July	23	2	25
2015 June	11	0	11
2015 May	23	5	28
2015 April	27	7	34
2015 March	16	5	21
2015 February	17	4	21
2015 January	25	8	33
2014 December	34	10	44
2014 November	23	6	29
2014 October	34	7	41
2014 September	31	8	39
2014 August	29	3	32
2014 July	21	7	28
2014 June	17	10	27
2014 May	18	12	30
2014 April	24	61	85
2014 March	19	5	24
2014 February	13	2	15
2014 January	16	3	19
2013 December	31	6	37
2013 November	22	3	25
2013 October	23	8	31
2013 September	0	1	1
2013 June	1	0	1

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