Cirugía aditiva corneal en estroma profundo con segmentos intraestromalesestudio clínico, biofísico, histólogo y modulación

Resumo

Introducción La cirugía de implantación de los segmentos intraestromales de polimetilmetacrilato (PMMA) se ha definido como una técnica refractiva reversible y reajustable para el tratamiento del queratocono, degeneración marginal pelúcida, ectasias secundarias al laser excimer, astigmatismo irregulares tras traumatismos corneales, astigmatismo tras queratoplastia y corrección de la miopía en córneas delgadas. Existen numerosos estudios que analizan la respuesta clínica y óptica tras la implantación de los segmentos intraestromales. Sin embargo, no se han descrito muchos datos en relación a la respuesta cicatricial corneal tras este procedimiento y tras la combinación con otras técnicas como el Cross Liking del colágeno corneal (CCL: Corneal Cross Linking). El conocimiento de este proceso puede contribuir a mejorar la seguridad y la eficacia de este tipo de cirugías refractivas y evitar complicaciones. Contenido de la investigación Objetivo: Evaluar la respuesta clínica, biofísica e histológica de la córnea de un modelo animal experimental tras la implantación y explantación de segmentos intraestromales de sección triangular en estroma profundo, la combinación con la técnica del CCL del colágeno corneal y la modulación, estimulando la respuesta celular al implante con el Plasma Rico en Factores de crecimiento (PRGF: Plasma Rich in Growth Factors) y con segmentos de nuevos materiales. Material y métodos: Se realizó cirugía en 286 ojos de gallinas (Gallus Gallus Domesticus). En 152 ojos se implantó un segmento en cada ojo para establecer el modelo que se caracterizó clínica e histológicamente. Treinta y ocho ojos sirvieron para estudios de reversibilidad analizando la respuesta corneal a la explantación del segmento implantado. En 18 ojos se implantaron los segmentos de forma invertida. En 48 ojos se combinó la implantación con CCL antes o después, en 30 ojos se estudiaron los efectos de la combinación de segmentos con PRGF y en 60 ojos se comparó la respuesta corneal ante segmentos de materiales diferentes al PMMA como el PEG (Polietilenglicol) y MMA/EHA (Metil metacrilato/ Etilexil acrilato). Se realizó seguimiento clínico de todos los ojos hasta su sacrificio y se realizaron medidas biofísicas de la refracción y transmitancia directa en tiempos seleccionados. Las gallinas de cada grupo sin complicaciones se dividieron aleatoriamente en varios grupos en función del tiempo de sacrificio, el procesado de las córneas y el análisis histológico con técnicas de microscopía básica, técnicas de inmunofluorescencia para estudio de proliferación, diferenciación y apoptosis y microscopía electrónica. También se realizaron medidas cuantitativas de distancias y número de células a partir de las fotos de las preparaciones de hematoxilina-eosina que se compararon entre los diferentes tiempos del modelo y entre el modelo y las diferentes modificaciones del mismo. Resultados: En los experimentos para establecer el modelo experimental desde el punto de vista clínico se observó precozmente el cierre de la herida epitelial con un edema corneal leve en la zona del canal durante los 15 primeros días. A los 4 meses todas las córneas tenían depósitos a lo largo de la curvatura interna, externa y por debajo. Se observó hace corneal solo en la incisión. La refracción cambió tras la implantación de los segmentos aumentando la hipemetropia sin cambios en la transmitancia directa de la córnea central. Histológicamente, se detectó apoptosis epitelial y estroma alrededor del segmento con un pico a las 12 horas y continuando hasta las 72 horas y reducirse posteriormente. La proliferación epitelial y estromal fue evidente desde las 12 , 24 horas con un pico a los 7 días y 72 horas respectivamente y prolongándose hasta los 6 meses alrededor del segmento. Se evidenció diferenciación a miofibroblastos al mes y tres meses de la implantación. También se describe una rotación del segmento en el estroma aproximándose el lado más próximo al limbo al epitelio, movimiento que se estabiliza al mes de la implantación y coincide con el mayor número de células alrededor del segmento. En los experimentos de reversibilidad, un mes después de la explantación se recupera el error refractivo preoperatorio permaneciendo cambios clínicos e histológicos en estroma profundo hasta el final del estudio. Al combinar la implantación de segmentos con el CCL antes y después; se observan menos depósitos y de menor intensidad en comparación con los depósitos observados en los ojos del modelo experimental. Histológicamente se observó menor grosor corneal y rotación del segmento cuando se realizaba el CCL previo a la implantación. El CCL tras la implantación de los segmentos tiene más efecto si se realiza próximo a la implantación. Al combinar la implantación con PRGF; clínicamente se observaron más depósitos a los 7 días que en el grupo del modelo experimental. Histológicamente, a las 48 horas hay menor afectación del grosor epitelial sobre el segmento en el grupo de PRGF. A los 7 días existe un mayor número de células alrededor del segmento con mayor contracción de la herida y mayor rotación del segmento en el grupo de PRGF. Al mes no existen diferencias estadísticamente significativas entre los dos grupos. Además, en los segmentos implantados con PRGF existió menor cambio refractivo que en el grupo de los segmentos implantados sin PRGF. Al comparar los diferentes materiales se observa mejor respuesta clínica e histológica en el grupo de MMA/EHA que en el resto de los grupos junto con mayor cambio refractivo. Conclusiones: Se ha desarrollado un modelo experimental animal de cirugía aditiva corneal de implantación de segmentos intraestromales en estroma profundo en la gallina con hallazgos clínicos y refractivos similares al humano. La respuesta cicatricial a estas heridas intracorneales profundas conlleva a una reorganización del colágeno y los queratocitos con muy poca diferenciación celular, lo cual produce un reforzamiento y engrosamiento de la misma sin pérdida de la transparencia. También se ha descrito la reversibilidad desde el punto de vista refractivo pero no clínico ni histologíco, permaneciendo cambios en el estroma profundo tras la explantación. El CCL del colágeno corneal previo a la implantación de los segmentos limita los efectos refractivos esperados de la implantación de segmentos y cuando se realiza tras la implantación, tiene un efecto aditivo si se realiza durante los primeros días . El PRGF inoculado en el túnel intraestromal tras la implantación de los segmentos intraestromales mejora la respuesta cicatricial durante los siete primeros días tras la cirugía. El MMA/EHA 90:10 presenta una mejor respuesta en vivo que el clásico PMMA (polimetilmetacrilato). La respuesta cicatricial tras la implantación de los segmentos intraestromales se modifica con la forma del segmento, profundidad y composición del material Bibliografía 1. J C. Técnicas de modelado corneal. 1 ed: Sociedad Española de Cirugía ocular implanto refractiva; 2009:479. 2. Krachmer JH. MM, Holland EJ. Cornea, Fundamentals, Diagnosis and Management. 3rd ed. USA: Mosby; 2011:1317. 3. Buck RC. 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