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Tesis Cristina Sánchez Barahona.Pdf m Univers�dad ::·:·:·.W/::·:·:·. de Alcala COMISIÓN DE ESTUDIOS OFICIALES DE POSGRADO Y DOCTORADO ACTA DE EVALUACIÓN DE LA TESIS DOCTORAL Año académico 2019/20 DOCTORANDO: SÁNCHEZ BARAHONA, CRISTINA PROGRAMA DE DOCTORADO: D420-CIENCIAS DE LA SALUD OPTO. COORDINADOR DEL PROGRAMA: BIOLOGÍA DE SISTEMAS TITULACIÓN DE DOCTOR EN: DOCTOR/A POR LA UNIVERSIDAD DE ALCALÁ En el día de hoy 05/11/19, reunido el tribunal de evaluación nombrado por la Comisión de Estudios Oficiales de Posgrado y Doctorado de la Universidad y constituido por los miembros que suscriben la presente Acta, el aspirante defendió su Tesis Doctoral, elaborada bajo la dirección de MIGUEL ANGESL TEUS GUEZALA // GEMA BOLIVAR DE MIGUEL. Sobre el siguiente tema: ESTUDIO DE LOS EFECTOS DEL TRATAMIENTO CON ANÁLOGOS DE LAS PROSTAGLANDINAS SOBRE LAS PROPIEDADES BIOMECÁNICAS CORNEALES Finalizada la defensa y discusión de la tesis, el tribunal acordó otorgar la CALIFICACIÓN GL0BAL1 de (no apto, aprobado, notable y sobresaliente): So 8�.ESA- L ( lVTf Alcalá de Henares, ...� ....... de .. �.�.�./.�1 ... de 1�.!..� ·< ...) < u ...) < El PRESIDENTE El V00�l UJ e, e, < e, V> <t: UJ > Fdo.: JULIÁN GARGÍA FEIJOÓ Fdo.:FRANCISCO J MUÑOZ NEGRETE z ;:, Con fecha_f.:?._de.ílOYi_(b.\.b_{t_dc_ctQJ�la Comisión Delegada de la Comisión de Estudios Oficiales de Posgrado, a la vista de los votos emitidos de manera anónima por el tribunal que ha juzgado la tesis, resuelve: JS{J Conceder la Mención de "Cum Laude" O No conceder la Mención de "Cum Laude" La Secretaria de la Comisión Delegada 1 la calificación podrá ser "no apto" "aprobado" "notable" y "sobresaliente". El tribunal podrá otorgar la mención de "cum laude" si la calificaciónglobal es de sobresaliente y se emite en tal sentido el voto secreto positivo por unanimidad. ESCUELA DE DOCTORADO Servicio de Estudios Oficiales de Posgrado DILIGENCIA DE DEPÓSITO DE TESIS. Comprobado que el expediente académico de D./Dª ____________________________________________ reúne los requisitos exigidos para la presentación de la Tesis, de acuerdo a la normativa vigente, y habiendo presentado la misma en formato: soporte electrónico impreso en papel, para el depósito de la misma, en el Servicio de Estudios Oficiales de Posgrado, con el nº de páginas: __________ se procede, con fecha de hoy a registrar el depósito de la tesis. Alcalá de Henares a _____ de ___________________ de 20_____ Fdo. El Funcionario Programa de Doctorado en CIENCIAS DE LA SALUD de la UAH ESTUDIO DE LOS EFECTOS DEL TRATAMIENTO CON ANÁLOGOS DE LAS PROSTAGLANDINAS SOBRE LAS PROPIEDADES BIOMECÁNICAS CORNEALES. Tesis Doctoral presentada por Cristina Sánchez Barahona 2019 Programa de Doctorado en CIENCIAS DE LA SALUD de la UAH ESTUDIO DE LOS EFECTOS DEL TRATAMIENTO CON ANÁLOGOS DE LAS PROSTAGLANDINAS SOBRE LAS PROPIEDADES BIOMECÁNICAS CORNEALES. Tesis Doctoral presentada por Cristina Sánchez Barahona Director: Prof. D. Miguel Ángel Teus Guezala Codirector: Dra. Gema Bolívar de Miguel Alcalá de Henares, 2019 A mi familia AGRADECIMIENTOS Al Profesor Miguel Ángel Teus. Por brindarme la posibilidad de realizar esta Tesis Doctoral. Por su gran aportación en mi aprendizaje y formación profesional. A la Doctora Gema Bolívar de Miguel. Por su implicación esta Tesis Doctoral y su dedicación en todos los proyectos emprendidos en común. A todos mis compañeros de residencia y adjuntos del Hospital Príncipe de Asturias, porque con ellos comencé el camino de esta profesión, cuatro años de incesante aprendizaje profesional y personal. A todos los compañeros con los que he coincidido en diferentes hospitales y a mis actuales compañeros de trabajo del Hospital de Getafe, porque de todos ellos he aprendido. A mis padres por inculcarme la importancia del esfuerzo, la dedicación y el amor. A Kiko, por todos estos años compartidos de comprensión y apoyo incondicional. Estudio de los efectos del tratamiento con análogos de las prostaglandinas sobre las propiedades biomecánicas corneales. RESUMEN INTRODUCCIÓN: La neuropatía óptica glaucomatosa (NOG) es una enfermedad multifactorial y una de las principales causas de disfunción visual y ceguera en el mundo. La evaluación de la presión intraocular (PIO) es esencial en los pacientes glaucomatosos por ser el único factor de riesgo modificable terapeúticamente. Actualmente la tonometría de aplanación Goldmann (TAG) es el “Gold stándard” para la medida de la PIO y la córnea juega un papel importante en la medida de la misma. Varios estudios sugieren que el espesor corneal central (ECC) y las propiedades biomecánicas corneales podrían afectar a la precisión de la TAG. Además, se ha descrito que el tratamiento con análogos de prostaglandinas (PGs), fármacos de primera línea en pacientes glaucomatosos e hipertensos oculares, modifica el ECC y puede inducir cambios histológicos en el colágeno y en la matriz extracelular corneal. El Ocular Response Analyzer (ORA) y el tonómetro Corvis ST son tonómetros de no contacto que proporcionan medidas de la PIO y además permiten evaluar algunas de las propiedades biomecánicas corneales “in vivo”. El objetivo del presente proyecto es evaluar si el tratamiento tópico con PGs en pacientes afectos de glaucoma primario de angulo abierto (GPAA) o hipertensión ocular (HTO) produce cambios en las propiedades viscoelásticas de la córnea y si dichos cambios biomecánicos pudieran artefactuar la medida de la PIO con TAG en estos pacientes. MATERIAL Y MÉTODOS: Se realizó un estudio transversal y dos estudios prospectivos (Estudio Prospectivo A y Estudio prospectivo B). Además, se incluyeron tres análisis intermedios. I ______________________________________________________________________ Resumen Estudio de los efectos del tratamiento con análogos de las prostaglandinas sobre las propiedades biomecánicas corneales. El estudio transversal incluye un total de 390 pacientes con GPAA o HTO en tratamiento con PGs, que de forma consecutiva acudieron a la consulta de glaucoma. A todos los pacientes se les realizó además de una Historia Clínica y exploración ocular completa, una TAG, paquimetría ultrasónica, Campo Visual (CV) y ORA. En el estudio prospectivo A (estudio prospectivo, observacional) 68 ojos de 68 pacientes recién diagnosticados de GPAA o HTO fueron evaluados mediante TAG, paquimetría ultrasónica, CV y ORA, antes y 6 meses después de iniciar tratamiento con PGs. En el estudio prospectivo B (estudio prospectivo, observacional) se evaluaron las propiedades biomecánicas corneales y la PIO en 67 ojos de 67 pacientes recién diagnosticados de GPAA o HTO mediante TAG, ORA y Corvis ST, realizados antes de iniciar el tratamiento con PGs , a los 3 y a los 6 meses tras iniciar el tratamiento con PGs. En ambos estudios prospectivos ninguno de los pacientes había recibido previamente tratamiento hipotensor tópico. RESULTADOS: En el estudio transversal encontramos una fuerte y significativa correlación entre la PIOg (Presión intraocular correlacionada-Goldmann) y la PIO cc (Presión intraocular Corneo-Compensada) (p=0.0001, r2=0.9) y una débil correlación de la PIOg con la PIO GAT (p=0.0001,r2=0.41) y con la Histéresis Corneal (HC) (p=0.0006,r2=0.03). Respecto a los estudios prospectivos sólo encontramos una correlación estadísticamente significativa de la desviación media (DM) del CV con la HC (p=0.003, r2=0.16) y con el ECC (p=0.03, r2=0.08) en los pacientes con GPAA. La PIOcc fue significativamente mayor que la PIO GAT en los GPAA (p=0.002) mientras que no se encontaron diferencias significativas entre ambos tonómetros en los HTO (p=0.5). No encontramos ninguna diferencia estadísticamente significativa en la medida del descenso de PIO tras II ______________________________________________________________________ Resumen Estudio de los efectos del tratamiento con análogos de las prostaglandinas sobre las propiedades biomecánicas corneales. tratamiento entre PIO GAT y PIO cc, mientras que el descenso de PIO medido mediante Corvis ST fue estadísticamente diferente (p=0.0001). La HC aumentó significativamente (p=0.0001), y este incremento se correlacionó significativamente con la HC basal (p=0.0001, r=0.64, r2=0.41). Además, se identificó una débil pero significativa correlación entre la HC basal y la reducción de la PIO GAT (r2=0.06, p=0.01) tras el tratamiento con PGs. Sin embargo, el incremento de la HC no se correlacionó con el descenso de la PIO GAT. Finalmente, encontramos cambios estadísticamente significativos tras 6 meses de tratamiento con PGs en el primer tiempo de aplanación corneal (AT1) (p=0,03), en el segundo tiempo de aplanación corneal (AT2) (p=0,02), en la máxima deformidad de amplitud (DA) (p=0,0002), en la primera velocidad de aplanación corneal (AV1) (p=0,003), en la distancia pico de la máxima concavidad (PD) (p=0,03), y en el radio de máxima concavidad (CCR) (p=0,03), medidos mediante Corvis ST. La magnitud del descenso de PIOcorvis (ΔPIO corvis) se correlacionó de forma significativa con el AT1 (p=0.001, r2=0.98), AT2 (p=0.0001, r2=0.52) y con la DA (p=0.001, r2=0.61). DISCUSIÓN: Hallamos que la PIOg se correlaciona más con la PIOcc que con la PIO TAG en pacientes con GPAA o HTO en tratamiento con hipotensores oculares tópicos. Además encontramos que la PIOcc es significativamente mayor que la PIO GAT en pacientes recién diagnosticados de GPAA que no han recibido tratamiento previamente, mientras que no se encontaron diferencias significativas entre ambos tonómetros en los pacientes HTO. Esto sugiere, que la PIOg, medida con ORA, no se puede considerar equivalente a la PIO TAG en estos pacientes. También encontramos una correlación
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