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Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
Joaquín Fernández Pérez
1
Instituto Universitario de Física Aplicada a las Ciencias y las Tecnologías
Departamento de Óptica, Farmacología y Anatomía
Facultad de Ciencias de la Salud
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
Joaquín Fernández Pérez
Tesis presentada para aspirar al grado de
DOCTOR POR LA UNIVERSIDAD DE ALICANTE
DOCTORADO EN FÍSICA APLICADA A LAS CIENCIAS Y LAS TECNOLOGÍAS
Dirigida por:
Dr. David P Piñero Llorens
Alicante, abril 2017
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
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D. DAVID PABLO PIÑERO LLORENS, Doctor por la Universidad de Alicante, Investigador
Distinguido (Acreditado para titular en el área de Óptica) del Departamento de Óptica, Farmacología y
Anatomía de la Facultad de Ciencias de la Universidad de Alicante y miembro del Instituto Universitario
de Física Aplicada a las Ciencias y a las Tecnologías:
CERTIFICA: Que la presente memoria titulada “Cirugía refractiva láser corneal SMILE.
Resultados visuales y biomecánica corneal en miopías bajas, medias y altas” ha sido realizada bajo su
dirección por Don JOAQUÍN FERNÁNDEZ PÉREZ en el Instituto Universitario de Física Aplicada a las
Ciencias y a las Tecnologías de la Universidad de Alicante y constituye su Tesis Doctoral para optar al
Grado de Doctor.
Y para que conste, y en cumplimiento de la legislación vigente, firman el presente certificado en
Alicante a de junio de dos mil diecisiete.
Fdo. David P Piñero Llorens
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
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Agradecimientos
A David Piñero, por el que siento una profunda admiración por su trayectoria profesional,
sincero agradecimiento por su apoyo y con el que durante todo este tiempo he forjado una
entrañable amistad basada en el afecto y respeto mutuo.
Al Departamento de I+D+i de Qvision y en especial a su Director, Manuel Rodríguez, del que
tengo el constante privilegio de enriquecerme con su búsqueda del extremo rigor metodológico
en investigación, que ha sido un pilar básico en la elaboración de esta tesis y por el que profeso
una profunda admiración por su talento.
A todo el equipo asistencial de Qvision, sin los que con su excelencia en el trabajo diario, esta
tesis hubiera sido imposible realizar.
A Virginia y Carmen por su amor y por hacer de lo pequeño y cotidiano, lo imprescindible.
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
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Índice
ÍNDICE DE ABREVIATURAS .............................................................................................. 9
RESUMEN ............................................................................................................................. 13
SUMMARY ........................................................................................................................... 15
CAPÍTULO 1 ....................................................................................................................................... 17
1.1. Introducción la cirugía refractiva corneal. .................................................................. 19
1.2. Cambio de paradigma en la cirugía refractiva láser. .................................................. 19
1.2.1. El láser de femtosegundo en cirugía refractiva. 19
1.2.2. La creación de un lentículo intraestromal. 20
1.2.3. Técnica de extracción del lentículo en humanos (ReLEx). 21
1.2.4. Extracción del lentículo a través de una microincisión (SMILE). 21
1.3. Controversias en torno a SMILE frente a LASIK. ..................................................... 23
1.3.1. Sensibilidad corneal y sequedad ocular. 23
1.3.2. Tiempo de recuperación visual. 24
1.3.3. Resultados en función de las características del paciente o de la cirugía. 25
1.3.4. Calidad óptica ocular. 26
1.3.5. Biomecánica corneal. 28
1.4. Evaluación clínica de la biomecánica corneal. ........................................................... 29
1.4.1. Instrumentos clínicos para la medida de la biomecánica corneal. .............................. 29
1.4.2. Medida clínica de biomecánica corneal tras cirugía refractiva................................... 31
1.5. Justificación y objetivos. ............................................................................................ 32
1.6. Estructura de la Tesis. ................................................................................................ 34
CAPÍTULO 2 ....................................................................................................................................... 37
2.1. Short-term outcomes of Small Incision Lenticule Extraction (SMILE) for low,
medium and high myopia. ...................................................................................................... 41
2.1.1. Abstract ...................................................................................................................... 41
2.1.2. Introduction ................................................................................................................ 42
2.1.3. Methods ...................................................................................................................... 42
2.1.4. Results ........................................................................................................................ 45
2.1.5. Discussion .................................................................................................................. 50
______________________________________________________________________________________________
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2.1.6. Disclosures ................................................................................................................. 53
2.1.7. References .................................................................................................................. 53
2.2. Corneal thickness after SMILE affects Scheimpflug-based Dynamic Tonometry ..... 58
2.2.1. Abstract ...................................................................................................................... 58
2.2.2. Introduction ................................................................................................................ 59
2.2.3. Methods ...................................................................................................................... 60
2.2.4. Results ........................................................................................................................ 64
2.2.5. Discussion .................................................................................................................. 67
2.2.6. Disclosures ................................................................................................................. 70
2.2.7. References .................................................................................................................. 71
2.3. New parameters for evaluating corneal biomechanics and intraocular pressure
after SMILE by Scheimpflug-Based Dynamic Tonometry. ................................................... 75
2.3.1. Abstract ...................................................................................................................... 75
2.3.2. Introduction ................................................................................................................ 76
2.3.3. Methods ...................................................................................................................... 77
2.3.4. Results ........................................................................................................................ 80
2.3.5. Discussion .................................................................................................................. 83
2.3.6. Disclosures ................................................................................................................. 88
2.3.7. References .................................................................................................................. 89
CAPÍTULO 3 ....................................................................................................................................... 91
3.1 Discusión de los resultados. ....................................................................................... 93
CAPÍTULO 4 ....................................................................................................................................... 97
4.1 Cumplimiento de objetivos ........................................................................................ 99
4.2 Aportaciones realizadas y líneas futuras de investigación. ...................................... 100
BIBLIOGRAFÍA ................................................................................................................................ 103
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
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ÍNDICE DE ABREVIATURAS
Abreviatura Inglés Español
ASCRS American Society of Cataract and
Refractive Surgery
Congreso de la Academia Americana de
Oftalmología
A1 First applanation Primera aplanación
A2 Second applanation Segunda aplanación
AL1 Applanation length at A1 Longitud de aplanación en A1
AL2 Applanation length at A2 Longitud de aplanación en A2
AT1 Time to arrive at A1 Tiempo en alcanzar A1
AT2 Time to arrive at A2 Tiempo en alcanzar A2
ATR Against the rule En contra de la regla
AV1 Velocity to arrive at A1 Velocidad de aplanación en A1
AV2 Velocity to arrive at A2 Velocidad de aplanación en A2
bIOP Biomechanically corrected
intraocular pressure
Presión intraocular corregida por
parámetros biomecánicos
C Pupil size Tamaño de pupila
CBI Corneal Biomechanical Index Índice de Biomecánica Corneal
CCT Central Corneal Thickness Espesor corneal central
CCT’ Central Corneal Thickness after
surgery Espesor corneal central tras la operación
CD Corneal densitometry Densitometría corneal
CDVA Corrected distance visual acuity Agudeza visual con corrección
CH Corneal Hysteresis Histéresis corneal
CoST Corvis ST Corvis ST
CRF Corneal Resistance Factor Factor de resistencia corneal
DA Deformation Amplitude Amplitud de deformación en HC
DA’ Deformation Amplitude after
surgery
Amplitud de deformación en HC tras
cirugía
DAc DA corrected Deformación en máxima corregida,
preoperatoria más espesor corneal
DAR Deflection Amplitude Ratio Cociente de amplitud de deformación
DAR1
Ratio of the central corneal
deflection and the average of two
points located at one millimeter at
both sides from the center
Cociente de la amplitud de deformación
en el centro de la córnea y el promedio de
dos puntos a 1 mm de ambos lados
respecto al centro.
DAR2 Ratio of the central corneal
deflection and the average of two
Cociente de la amplitud de deformación
en el centro de la córnea y el promedio de
______________________________________________________________________________________________
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points located at two millimeters at
both sides from the center
dos puntos a 2 mm de ambos lados
respecto al centro.
DI Densitometry increase Incremento de la densitometría
DI-A1 Densitometry increase at A1 Incremento de la densitometría en A1
DI-A2 Densitometry increase at A2 Incremento de la densitometría en A2
DI-HC Densitometry increase at HC Incremento de la densitometría en HC
DIM Maximum Densitometry Increase Incremento de la densitometría máximo a
lo largo de la deformación
epi-LASIK Epithelial laser in-situ
keratomileusis
LASIK con separación del epitelio
mediante un epiqueratomo
EV Error Vector Vector de error
FLEx Femtosecond Lenticule Extraction Extracción del lentículo por
femtosegundo
FS-LASIK Femtosecond LASIK LASIK por femtosegundo
FS-LASIK WF Wavefront guided femtosecond
LASIK LASIK guiado por frente de onda
HC Highest Concavity Máxima concavidad
ICC Intraclass correlation index Índice de correlación intraclase
IOP Intraocular pressure Presión intraocular (PIO)
IR Integrated Inverse Concave Radius Integral del radio de concavidad
IRC Intended Refractive Correction Error refractivo a programado para
corrección
LASEK Laser-Assisted Subepitelial
Keratomileusis
Queratomileusis subepitelial asistida por
láser
LASIK Laser Assisted in-situ
Keratomileusis
Queratomileusis asistida mediante láser
Excímer
LRS Laser Refractive Surgery Cirugía refractiva láser
MTF Modulation Transfer Function Función de Transferencia de modulación
Nd-YAG Neodymium-doped yttrium
aluminium garnet -
NEV Normalized Error Vector Vector error normalizado
ORA Ocular Response Analyzer -
PA1 Air puff pressure at A1 Presión del pulso en A1
PA2 Air puff pressure at A2 Presión del pulso en A2
PD Peak distance Distancia entre picos
PERK Prospective Evaluation of Radial
Keratotomy -
PIO Intraocular pressure (IOP) Presión intraocular
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
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PRK Photorefractive Keratotomy Queratectomía fotorrefractiva
r Pearson r Coeficiente de Pearson
ReLEx Refractive Lenticule Extraction Extracción refractiva de lentículo
RK Radial Keratotomy Queratotomía radial
Rx Preoperative spectacle refraction Refracción preoperatoria en gafa
SCI Science Citation Index Índice de citas científicas
SD Standard Deviation Desviación Estándar
SE Spherical Equivalent Equivalente esférico
SimK Simmulated Keratometry Queratometría Simulada
SMILE Small Incision Lenticule
Extraction
Extracción refractiva de lentículo por
pequeña incisión
SP-A1 Stiffness parameter at first
applanation
Parámetro de rigidez en la primera
aplanación
t1 and t2
Indexes obtained from the ratio
between the change in time and
change in thickness
Índices obtenidos mediante el cociente
entre el cambio en tiempo frente al
cambio en espesor
TEV Treatment Error Vector Vector error de tratamiento
UDVA Uncorrected distance visual acuity Agudeza visual sin corrección
VA Visual acuity Agudeza visual
WTR With the Rule A favor de la regla
ZO Optic Zone Zona óptica
α Error probability Probabilidad de error
Δ Difference preoperative value –
postoperative value
Diferencias entre valores preoperatorios
y posoperatorios
δ Means Medias
ρ Spearman rho Rho de Spearman
σ Standard deviation Desviación estándar
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
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RESUMEN
La técnica de cirugía refractiva láser a través de la extracción de un lentículo por una
microincisión SMILE (Small Incision Lenticule Extraction), representa una técnica novedosa
para la corrección de la miopía y un cambio de paradigma en torno a los procedimientos
anteriores de cirugía refractiva láser. Como cualquier nueva técnica que irrumpe en una
especialidad de la medicina, se ve sometida al juicio de la evidencia científica con el fin de
demostrar las hipótesis planteadas desde el marco teórico. Este hecho es si cabe más destacable
en procedimientos que podrían suponer el reemplazo de técnicas llevadas a cabo con
anterioridad, como es el caso de SMILE frente a LASIK (Laser Assisted in-situ Keratomileusis)
y PRK (Photorefractive Keratotomy).
En esta Tesis doctoral por compendio de publicaciones se ponen de manifiesto las actuales
controversias en torno a las ventajas de SMILE frente a técnicas previas. Los resultados de
eficacia, seguridad y predictibilidad para las primeras intervenciones de un cirujano
experimentado en cirugía refractiva sin experiencia previa en SMILE son evaluadas en función
del nivel del error refractivo. Estos resultados clínicos podrían estar condicionados por las
características biomecánicas de la córnea intervenida. La influencia de la biomecánica corneal
en los resultados refractivos, junto con la detección de alteraciones corneales que pudiesen
derivar en el desarrollo de una ectasia corneal, representan dos de los motivos por los cuales
medir la biomecánica de manera fiable sería de gran importancia en la toma de decisiones del
cirujano refractivo.
Además, una de las controversias más polémicas debido a su falta de evidencia en investigación
clínica es la mayor preservación de la biomecánica corneal en SMILE frente a otras técnicas. En
esta Tesis doctoral se estudian las variables de confusión en pacientes operados de SMILE y se
proponen soluciones para el diseño de estudios con el fin de minimizar el efecto de éstas y así
poder detectar cuando los cambios en los parámetros de biomecánica se deben a una
modificación de la rigidez corneal y no a un cambio en las variables de confusión. Finalmente,
se analizan los parámetros más actuales de la tonometría dinámica de Scheimpflug con el fin de
determinar cuáles deberían ser o no corregidos ante las variables de confusión y se propone una
nueva variable conocida como densitometría dinámica por su posible aportación de información
sobre la biomecánica e hidratación corneal.
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
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SUMMARY
The technique of laser refractive surgery consisting of the removal of a lenticule by a micro
incision SMILE (Small Incision Lenticule Extraction) represents a novel technique for the
correction of myopia and a paradigm shift around previous procedures of laser refractive
surgery. Like any new technique that breaks into a specialty of medicine, it is submitted to the
judgment of the scientific evidence in order to demonstrate the hypotheses raised from the
theoretical framework. This fact is perhaps more remarkable in procedures that could involve
the replacement of techniques carried out previously, as in the case of SMILE against LASIK
(Laser Assisted in-situ Keratomileusis) and PRK (Photorefractive Keratotomy).
In this doctoral Thesis by compendium of publications, the current controversies regarding the
advantages of SMILE in relation to previous techniques are revealed. The results of efficacy,
safety and predictability for the first interventions of a surgeon experienced in refractive surgery
without previous experience in SMILE are evaluated according to the level of refractive error.
These clinical results could be conditioned by the biomechanical characteristics of the operated
cornea. The influence of corneal biomechanics on refractive outcomes, along with the detection
of corneal alterations that could lead to the development of corneal ectasia, represent two of the
reasons why reliable biomechanical measurement would be of great importance in the decision
making process of the refractive surgeon.
Furthermore, one of the most polemical controversies due to its lack of evidence in clinical
research is the greater preservation of corneal biomechanics in SMILE compared to other
techniques. In this doctoral Thesis we study the confounding variables in patients operated on
SMILE and propose solutions for the design of studies in order to minimize the effect of these,
and in addition to be able to detect when the changes in biomechanical parameters are due to a
modification of the corneal stiffness and not to a change in the confounding variables. Finally,
the current parameters of the Scheimpflug dynamic tonometry are analyzed in order to
determine which of them should be corrected or not to the confounding variables and a new
variable known as dynamic densitometry is proposed for its possible contribution of information
on biomechanics and corneal hydration.
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
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CAPÍTULO 1 INTRODUCCIÓN GENERAL
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
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1.1. Introducción la cirugía refractiva corneal.
La mayor parte de los procedimientos de cirugía refractiva llevados a cabo durante la
década de los 80 y 90 se centraban en tres técnicas principales: la queratotomía radial (RK,
Radial Keratotomy), la queratomileusis asistida mediante láser excimer (LASIK, Laser Assisted
in-situ Keratomileusis) y la queratectomía fotorrefractiva (PRK, Photorefractive Keratotomy)
(Corcoran 2015). La primera de ellas consistía en la ejecución de una serie de 4, 6, 8 o 16
incisiones radiales distribuidas de manera simétrica alrededor de la córnea excluyendo la región
central (zona óptica) de tal manera que a menor tamaño de zona óptica y mayor número de
incisiones, mayor era el efecto alcanzado por la cirugía (Holladay 2003). Esta técnica demostró
ser efectiva a largo plazo (10 años) en el 70% de los pacientes intervenidos con un nivel de
seguridad razonable y con una regresión hacia la hipermetropía que continuaba tras la década
del procedimiento (Waring et al. 1994). La RK pasó a un segundo plano a mediados de la
década de los 90 tras los resultados obtenidos por el estudio PERK (Prospective Evaluation of
Radial Keratotomy) en los que se hacía referencia a variaciones diurnas de la visión y presencia
de halos (Kemp et al. 1999), creciendo en popularidad al mismo tiempo las técnicas PRK y
LASIK con la introducción del láser excimer de 193 nm a principios de los 90 (Sher et al. 1991;
Carr et al. 2001).
La técnica PRK consiste en utilizar luz ultravioleta de 193 nm, a través de un láser
excimer, con el fin de fotoablacionar tejido estromal sin afectar en gran medida a las regiones
circundantes a la zona de aplicación. Para ello, se elimina el epitelio completamente en la zona
óptica antes de la aplicación del láser o se retira el epitelio para ser posteriormente
reposicionado, esta variante de la PRK se conoce como queratomileusis subepitelial asistida por
láser (LASEK, Laser-Assisted Subepitelial Keratomileusis)(Ghadhfan et al. 2007). A diferencia
de la PRK y pese a utilizar el mismo láser para realizar la ablación corneal, la técnica LASIK
conlleva la creación de un flap corneal que se mantiene ligado a la córnea en forma de bisagra y
que se reposiciona tras la aplicación del láser. El LASIK posee importantes ventajas frente a la
PRK (disminución de la prevalencia de opacidades corneales (haze), eliminación del dolor
postoperatorio, etc.)(Holladay 2003) que han supuesto que esta técnica se convirtiese en la
preferida por gran parte de los cirujanos refractivos (Corcoran 2015).
1.2. Cambio de paradigma en la cirugía refractiva láser.
1.2.1. El láser de femtosegundo en cirugía refractiva.
En el apartado anterior realizamos una introducción a las técnicas principales de cirugía
______________________________________________________________________________________________
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refractiva láser. Pese a que podemos encontrar variantes en la literatura científica sobre éstas
técnicas, como el uso de mitomicina C en la PRK para prevenir el haze en altas miopías
(Gambato et al. 2005), la separación del epitelio mediante un epiqueratomo (epi-
LASIK)(Pallikaris et al. 2005), LASIK o LASEK guiado por frente de onda (Schwiegerling
2004; Jung et al. 2015), etc., la realidad es que estas variantes continúan siendo llevadas a cabo
con láser excimer. No fue hasta principios de los 90 cuando otros láseres aparecieron con
frecuencias de pulso del nanosegundo (ns, 10-9s), picosegundo (ps, 10-12s) y femtosegundo (fs,
10-15s) para longitudes de onda del visible y del infrarrojo corto como posible alternativa al láser
excimer (Stern et al. 1989). La principal ventaja de incrementar la frecuencia del pulso desde el
ns al fs reside en una disminución del daño producido en los tejidos circundantes (Soong &
Malta 2009). De esta forma conseguimos que, a diferencia del láser Nd:YAG que utiliza una
longitud de onda en el infrarrojo corto (1064 nm) y una frecuencia de ns produciendo un daño
colateral de hasta 100 µm, empleando una longitud de onda similar (1053 nm) en fs podamos
trabajar sobre la córnea ya que el volumen colateral de tejido dañado es 103 veces menor en fs
que ps (frecuencia mayor al ns del Nd:YAG)(Stern et al. 1989).
1.2.2. La creación de un lentículo intraestromal.
Los nuevos láseres de fs permitieron actuar de distinta forma sobre el tejido corneal. En
la Tabla 1 se muestra un resumen de los principales láseres utilizados en oftalmología, su
longitud de onda y el efecto que producen sobre el tejido en el que actúan. El láser excimer
actúa de manera no localizada fotoablacionando el tejido superficial sobre el que incide, bien
sea tras retirar el epitelio (PRK) o tras realizar un flap accediendo a una capa más profunda del
estroma (LASIK). No obstante, el modo de actuación del láser de fs sobre la córnea es
totalmente diferente. Permite trabajar de manera localizada, dentro o incluso detrás de la córnea,
de tal forma que se generan pequeñas burbujas separadas un pequeño espacio (fotodisrupción)
creando un corte que alcanza alrededor de 1 µm en precisión (Soong & Malta 2009).
Tabla 1. Listado de láseres empleados en oftalmología (Soong & Malta 2009).
Láser Longitud de onda (nm) Efecto en el tejido
Dióxido de carbono
Nd:YAG
Femtosegundo
Kriptón
Argón
Excimer
10600 (infrarrojo largo)
1064 (infrarrojo corto)
1053 (infrarrojo corto)
647-531 (visible)
514-488 (visible)
193 (ultravioleta largo)
Fototermal
Fotodisrupción
Fotodisrupción
Fotoquímico (coagulación)
Fotoquímico (coagulación)
Fotoablación
Láser Nd-YAG (acrónimo del inglés neodymium-doped yttrium aluminium garnet)
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
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La hipótesis de la posible cirugía refractiva intraestromal planteada a principios de los
90 por varios autores con la esperanza de mantener intactos el epitelio, la membrana de
Bowman y el endotelio era cada vez más real con la llegada del láser de fs (Kurtz et al. 1998).
Con anterioridad, varios intentos habían sido llevados a cabo con láseres de ns y ps (Vogel et al.
1994; Krueger et al. 1996). No obstante, el daño colateral producido limitaba la capacidad de
obtener una ablación eficiente y predecible incluso en el caso del ps en el que se producía un
menor daño colateral, pero se requería una disección manual que terminaba originando una
superficie irregular (Ito et al. 1996).
1.2.3. Técnica de extracción del lentículo en humanos (ReLEx).
En el año 2003 se realizó el primer estudio en humanos que implicaba el tallado de un
lentículo intra-estromal, resultando en córneas transparentes tras las primeras dos horas y
resultados refractivos estables (Ratkay-Traub et al. 2003). No obstante, no fue hasta el año 2007
cuando se introdujo el primer laser comercial (VisuMax, Carl Zeiss Meditec, AG, Jena,
Germany) para la corrección de la miopía a través de la generación de un lentículo intraestromal
(Reinstein et al. 2010). Esta técnica recibió el nombre de Refractive Lenticule Extraction
(ReLEx) por la generación del lentículo, mientras que la extracción del mismo se llevaba a cabo
previo tallado de un flap corneal similar al del LASIK, procedimiento que se pasó a llamar
Femtosecond Lenticule Extraction (FLEx) (Sekundo et al. 2008). Los resultados preliminares de
la técnica se llevaron a cabo en 10 ojos miopes durante un periodo de seguimiento de 6 meses,
los cuales demostraron ser prometedores, siendo éste el origen del cambio de paradigma en la
cirugía refractiva láser corneal (Sekundo et al. 2008). Como en cualquier inicio, la técnica no
estaba exenta de posibilidades de mejora, entre ellas el tiempo de recuperación visual que
demostró estar influenciado por la dirección en la ejecución del tallado del lentículo (Shah &
Shah 2011).
1.2.4. Extracción del lentículo a través de una microincisión (SMILE).
La técnica FLEx representaba tan solo una rápida transición hacia la que sería la cirugía
refractiva corneal mínimamente invasiva. En el año 2011, el procedimiento evolucionó a la
técnica Small Incision Lenticule Extraction (SMILE)(Sekundo et al. 2011). A diferencia de la
FLEx, la extracción del lentículo ya no se llevaría a cabo a través de la creación de un flap
corneal sino mediante la ejecución de una pequeña incisión por la que se extraería el lentículo.
La Figura 1 muestra cada uno de los pasos llevados a cabo durante la cirugía refractiva laser
SMILE para la corrección de la miopía. En la página EyeTube (https://eyetube.net/video/relex-
______________________________________________________________________________________________
22
smile-step-by-step--esweq/) puede visualizarse un video presentado en el Congreso de la
Academia Americana de Oftalmología (ASCRS) en el año 2015 por el autor de esta tesis
doctoral en el que se explica paso por paso el desarrollo de la técnica (Fernández 2015).
Los resultados de la cirugía SMILE han ido mejorando desde sus inicios. En la Tabla 2
se presenta una revisión de la literatura científica en términos de efectividad y predictibilidad
que demuestra una mejoría en los años 2013-2014 frente a los resultados obtenidos durante los
dos primeros años 2011-2012 (Reinstein et al. 2014). Algunas de las razones que podrían
explicar esta mejoría con el paso de los años podría residir en una mayor experiencia de los
cirujanos en el desarrollo de la técnica, ya que como podemos ver en la Figura 1, la técnica
SMILE posee diferentes pasos en los que la experiencia del cirujano podría ser clave. Por
ejemplo, antes de la acción del láser se requiere que el cirujano centre el cono que realizará
succión en el ojo (paso conocido como docking) sobre la pupila del paciente o el vertex corneal
(Li et al. 2014), además de ser necesaria una intervención manual durante la disección de las
superficies anterior y posterior del lentículo que podría estar relacionada con la presencia de
irregularidades en la membrana de Bowman, conocidas como microdistorsiones (Yao et al.
2013).
Figura 1. Pasos de la cirugía refractiva corneal SMILE durante la ejecución del láser: (1) tallado de la superficie posterior del lentículo o zona óptica; (2) tallado de la superficie anterior conocida como cap; (3) ejecución de la incisión en la parte inferior de la imagen correspondiente a la región superior-temporal del ojo. Durante el proceso quirúrgico: (4) delineación o reconocimiento de las superficies anterior y posterior del lentículo; (5) disección de la superficie anterior del lentículo; (6) disección de la superficie posterior del lentículo; (7) extracción del lentículo a través de la microincisión; (8) secado y regularización de la superficie.
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
23
Tabla 2. Resultados en términos de eficacia y predictibilidad en 2011/12 frente a 2013/14 (Tabla adaptada de (Reinstein et al. 2014).
Estudio Ojos Seguimiento ±0.50D AVsc >20/20 post AVsc >20/25 post
Sekundo 2011
Shah 2011
Vestegaard 2012
Hjortdal 2012
91
51
127
670
6 meses
6 meses
3 meses
3 meses
80%
91%
77%
80%
84%
62%
37%
61%
92%
79%
73%
84%
Promedio 2011/12 82% 61% 82%
Wang 2013
Kamiya 2014
Sekundo2014
Agca 2014
Lin 2014
88
26
54
40
60
3 meses
6 meses
1 año
1 año
3 meses
-
100%
92%
95%
-
100%
96%
88%
65%
85%
-
-
98%
95%
93%
Promedio 2013/14 96% 87% 95%
1.3. Controversias en torno a SMILE frente a LASIK.
1.3.1. Sensibilidad corneal y sequedad ocular.
La córnea es uno de los tejidos humanos periféricos con mayor densidad nerviosa. Una
analogía para entender de manera sencilla como se distribuyen los nervios dentro de la córnea es
visualizar el desarrollo de ramas y hojas de una Acacia tortilis (Figura 2). Haces gruesos de
nervios penetran en la periferia de la córnea, cerca del limbo esclerocorneal, a unas 293 ± 106
µm de profundidad con respecto a la superficie corneal (Figura 1a). Justo tras penetrar en la
córnea los haces principales se dividen de manera progresiva en nervios cada vez más pequeños
(plexo en estroma medio, Figura 2b). Muchos de estos nervios continúan incrementando su
densidad hacia la superficie (plexo subepitelial, Figura 2c). Algunos de estos pequeños nervios
penetran en el epitelio (plexo subbasal y terminales intraepiteliales, Figura 2d) (Marfurt et al.
2010).
______________________________________________________________________________________________
24
Figura 2. Analogía entre el crecimiento de una Acacia Tortilis y la ramificación nerviosa dentro de la
córnea conforme nos aproximamos a su superficie. Imagen a partir de (Marfurt et al. 2010) .
La sección de la córnea para la creación de un flap con el fin de aplicar el láser excimer
en cirugía LASIK conlleva la disección de gran parte de estas fibras nerviosas reduciendo la
sensibilidad corneal y con ello la producción de lágrima basal. El LASIK y la PRK provocan
una pérdida de la densidad nerviosa en el plexo subbasal del 51% y 59%, respectivamente, que
se recupera hasta diferencias no significativas con los valores preoperatorios a los dos años en
PRK y a los cinco en LASIK (Erie et al. 2005). En cuanto a la cirugía SMILE, encontramos
ciertas discrepancias en los periodos de recuperación pese a que los resultados siempre son
favorables a SMILE (He et al. 2015). Por ejemplo, Li reportó una pérdida menos severa que en
FS-LASIK durante los tres primeros meses (Li et al. 2013), mientras que Ishii encontró
diferencias significativas al año en FLEx con respecto a los valores preoperatorios, pero no en el
caso de SMILE (Ishii et al. 2015). En resumen, los meta-análisis coinciden en que la pérdida de
sensibilidad corneal y la sequedad ocular inducida por la cirugía es menor en SMILE que FS-
LASIK (Zhang et al. 2015; Shen et al. 2016; Kobashi et al. 2016).
1.3.2. Tiempo de recuperación visual.
El tiempo de recuperación visual tras la cirugía ha sido una de las desventajas de
SMILE frente a LASIK desde el nacimiento de la técnica. Pese a que el tiempo de recuperación
visual ha disminuido aplicando ciertas modificaciones dentro de la técnica como la dirección del
láser en el tallado del lentículo (Shah & Shah 2011), existe una gran variedad en los resultados
clínicos reportados por distintos autores sobre el porcentaje de sujetos que alcanzan agudeza
visual decimal unidad a las 24 horas del procedimiento (Tabla 3).
Esta elevada discrepancia entre estudios clínicos hace pensar sobre la influencia de la
habilidad del cirujano, del instrumental o de otras variables en el tiempo de recuperación visual
(Y. Liu et al. 2016). Agca reportó una mayor dispersión lumínica en SMILE que LASIK en la
interfaz del lentículo, hipotetizando que podría ser debido a imprecisiones en el corte del
lentículo por la configuración del láser (Agca, Ozgurhan, Yildirim, et al. 2014). Estos hallazgos
están en acuerdo con los resultados que demuestran una temprana recuperación visual llevando
la energía del láser a 100 nJ (nivel 20 del láser), en lugar de 180 nJ (nivel 36 del láser)(Donate
& Thaëron 2016), pero sin diferencias en términos de calidad visual, incluyendo scattering, para
comparativa de energías de 140 nJ y 170 nJ (Kamiya et al. 2015). Otros autores han encontrado
que reposicionando el cap tras la cirugía presionando la superficie y deslizando una espátula de
Seibel unas 20 veces de arriba hacia abajo obtenían un menor número de microdistorsiones,
presentes especialmente en altos errores refractivos (Luo et al. 2015), y una mejor función de
transferencia de modulación (MTF)(Shetty et al. 2016). Este gesto ayudaría a eliminar el líquido
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
25
alojado en el bolsillo donde se aloja el lentículo tras la irrigación efectuada para eliminar
desechos celulares que medien la inflamación (Liu et al. 2015).
Tabla 3. Porcentaje de sujetos que alcanzan una agudeza visual decimal unidad al día, 3
meses o 6 meses según diferentes estudios.
Estudio 1 día 3 meses 6 meses
(M. Liu, Chen, et al. 2016)
Frente a FS-LASIK*
(Xu & Yang 2015)
(Kim et al. 2014)
(Zhao et al. 2015)
(Shetty et al. 2016)
(Ganesh & Gupta 2014)
Frente a FS-LASIK*
(Kim et al. 2015)
Baja miopía
Alta miopía
(Donate & Thaëron 2016)
100 nJ (nivel 20)
180 nJ (nivel 36)
(Luo et al. 2015)
> -3.00D
-3.00D a -6.00D
< -6.00 D
55%
73%*
63%
54.4%
100%
100%
96%
88%*
65.5%
63.2%
66%
23%
88.2%
69.2%
65%
93%
96%
85%
-
-
-
-
-
87.5%
78.8%
-
-
-
-
-
96%
99%
-
79.8%
-
-
96%
88%*
-
-
-
-
-
-
-
*Comparativa con los resultados de LASIK incluidos en el mismo estudio.
1.3.3. Resultados en función de las características del paciente o de la cirugía.
Los estudios clínicos en los inicios de cualquier procedimiento de cirugía refractiva se
focalizan principalmente en determinar la seguridad, eficacia y predictibilidad de la técnica,
definiendo cada uno de estos parámetros como:
Seguridad, complicaciones tras la operación y comparativa de las agudezas
visuales pre y postoperatorias con corrección.
Eficacia, como la diferencia entre la agudeza visual preoperatoria con
corrección y la postoperatoria sin corrección.
Predictibilidad, correlación entre el error corregido y el que se ha programado
corregir o el porcentaje de sujetos con un cierto residual refractivo tras la
operación.
La cirugía refractiva SMILE ha demostrado, en términos generales, ser tan segura,
eficaz y predecible, como la cirugía refractiva FS-LASIK según se recoge en los dos principales
meta-análisis comparando ambas técnicas llevados a cabo hasta la fecha (Shen et al. 2016;
Zhang et al. 2015). No obstante, una vez asentado el conocimiento general de seguridad,
______________________________________________________________________________________________
26
eficacia y predictibilidad se hace necesario estudiar los resultados de la técnica de acuerdo a las
particularidades de cada caso con el fin de establecer el origen de posibles sesgos que puedan
empeorar los resultados visuales. Por ejemplo, se ha reportado que con el incremento de la edad
los resultados de agudeza visual sin corrección 6 meses tras la cirugía empeoran a razón de una
pérdida de 0.07 logMAR por década (Chansue et al. 2015). Además, las figuras de
predictibilidad que confrontan el error tratado con el error corregido por el procedimiento
muestran, en algunos estudios, una pendiente por debajo de la unidad que sugiere una
hipocorrección con el incremento de la miopía (Lin et al. 2014; Chansue et al. 2015), hecho no
visible en autores que utilizan su propio nomograma (Pradhan et al. 2016) o inclusive en otros
que no especifican utilizar un nomograma personalizado (Hansen et al. 2016). No obstante, se
han propuesto regresiones lineales para corregir la hipocorrección especialmente por encima de
las 6 D de miopía tras manifestar este grupo de pacientes un mayor regresión miópica al año
(W. Wu et al. 2016). Además se ha reportado la influencia de otras variables como la edad en
los resultados visuales (Kim et al. 2014; Hjortdal et al. 2012), mientras que muchas otras
variantes de la cirugía no tienen afectación en los resultados visuales: espesor del cap o
profundidad del lentículo entre 120 y 140 µm (M. Liu, Zhou, et al. 2016) o entre 130 y 160 µm
(Güell et al. 2015), y localización de la incisión temporal o superior (Chan et al. 2016).
1.3.4. Calidad óptica ocular.
Los resultados de eficacia de un procedimiento de cirugía refractiva se dan en términos
de agudeza visual como vimos en el apartado anterior. No obstante, dos procedimientos pueden
resultar en eficacia similar en términos de agudeza visual pero ofrecer distintos resultados en
términos de rendimiento visual al evaluar variables más sensibles a pequeños cambios en la
calidad óptica ocular (Rodríguez-Vallejo et al. 2015). Desde el punto de vista objetivo, podemos
emplear instrumentos como aberrómetros, topógrafos corneales y sistemas de doble paso con el
fin de medir la calidad óptica tras el procedimiento ante distintas condiciones de diámetro
pupilar (Donate & Thaëron 2016; Güell et al. 2015). De manera particular, el centrado manual
por parte del cirujano y la ausencia de eye-tracking han sido valorados como debilidades de la
técnica SMILE, que podrían derivar en la incidencia de un mayor número de aberraciones
corneales, especialmente coma secundario a una ablación descentrada durante el periodo de
aprendizaje (Li et al. 2014). Si bien es cierto que desde el punto de vista teórico se ha
argumentado que un descentramiento en SMILE no posee el mismo impacto en el incremento
de las aberraciones de alto orden que un descentramiento en LASIK o PRK (Bischoff &
Strobrawa 2016). Puesto que los meta-análisis no suelen incluir amplia información sobre la
calidad óptica y las aberraciones de alto orden tras SMILE frente a LASIK, hemos recogido
dentro de la tabla 4 muchos de los estudios que incluyen información sobre las aberraciones de
alto orden, principalmente coma y aberración esférica.
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
27
Tabla 4. Estudios que comparan las aberraciones inducidas por el procedimiento (Postoperatorio –
Preoperatorio) entre SMILE y LASIK.
Mes Autor Aberración SMILE (A) LASIK (B) A-B ZO / Pupila
6 m (Ye et al. 2016) Esférica
|Coma H|
|Coma V|
0.17*
0.08*
0.22*
0.29*
0.01
0.18*
-0.12*
0.07*
0.04*
6.0 mm (A)
6.0 mm (B)
6.0 mm (C)
6 m (M. Liu, Chen, et al.
2016)
Esférica
Coma
0.12 ± 0.22
0.20 ± 0.21
0.28 ± 0.26
0.24 ± 0.24
-0.16*
-0.04
6.5 mm (A)
NE (B)
6 mm (C)
3 m (Gyldenkerne et al.
2015)
Esférica
Coma
0.0072 ± 0.095
0.14 ± 0.15
0.15 ± 0.084
0.23 ± 0.20
-0.14*
-0.10*
6 a 6.5 mm (A)
6 mm (B)
5 mm (C)
3 m (Ganesh & Gupta
2014)
RMS 0.061 0.174 -0.113* 6 a 6.5 mm (A)
NE (B)
5 mm (C)
3 m (Lin et al. 2014) Esférica
Coma
RMS
0.273
0.396
0.117
0.689
0.193
0.204
-0.416*
+0.203*
-0.087*
6.36 ± 0.23 (A)
6.02 ± 0.19 (B)
NE (C)
6 m (Gao et al. 2014) Esférica
Coma
0.12 ± 0.22
0.20 ± 0.21
0.28 ± 0.26
0.24 ± 0.24
-0.16*
-0.04*
NE (A)
NE (B)
6 mm (C)
6 m (Li et al. 2015) Total
Esférica
|Coma H|
|Coma V|
0.619
0.298
0.456
0.149
0,801
0,397
0,503
0,522
-0,182
-0,099
-0,047
-0,373
6 mm (A)
6 mm (B)
6 mm (C)
3 m (Wu & Wang 2015) 3er a 6º
Esférica
|Coma H|
|Coma V|
> tras cirugía*
> tras cirugía*
> tras cirugía*
> tras cirugía*
> tras cirugía*
> tras cirugía*
> LASIK*
> LASIK*
> LASIK*
> SMILE*
6 mm (A)
6 mm (B)
6 mm (C)
3 m (Wu & Wang 2016) Total
Esférica
Coma
0.45*
0.26*
0.35*
0.55*
0.33*
0.4*
-0,1
-0,07
-0,05
6 a 6.5 mm (A)
6 a 6.5 mm (B)
6 mm (C)
3 m (Yu et al. 2015) Total
Esférica
Coma
> tras cirugía*
> tras cirugía
> tras cirugía*
> tras cirugía*
> tras cirugía*
> tras cirugía*
> LASIK*
> LASIK*
> SMILE
6.5- 6.6 mm (A)
6.25-6.75mm (B)
6 mm (C)
ZO es el tamaño de zona óptica para (A) SMILE o (B) LASIK mientras que (C) representa el tamaño de pupila para el cual se han calculado las aberraciones de alto orden. * Las diferencias son significativas entre el pre y el post o para las diferentes técnicas.
De la revisión llevada a cabo en 10 estudios que incluyen las aberraciones de alto orden
(Tabla 4) podemos concluir que la aberración esférica es mayor tras un procedimiento LASIK
que en SMILE, algo en lo que coinciden todos los estudios consultados. No obstante, existe
controversia en torno a la mayor inducción de coma en SMILE con 4 estudios que resultaron en
una mayor inducción y 5 estudios en los que la inducción de coma fue menor con respecto a
LASIK, por lo que es posible que la experiencia del cirujano en el centrado esté relacionada con
la inducción de una mayor aberración comática.
______________________________________________________________________________________________
28
1.3.5. Biomecánica corneal.
Tras la aparición de la técnica SMILE se hipotetizó que ésta preservaba de mejor forma
la biomecánica corneal en comparativa con la técnica LASIK (Reinstein et al. 2013). Esta
hipótesis se fundamenta en la organización que mantienen las fibras de colágeno en distintas
profundidades del estroma. En el estroma anterior las fibras de colágeno mantienen una mayor
angulación, penetrando en la membrana de Bowman y formando un entramado similar a la
estructura que soporta la parte inferior de un puente (del inglés Bow spring-like structure)
(Abass et al. 2015). Se ha reportado que esta angulación es notablemente más marcada en las 83
µm del estroma anterior y disminuye con la profundad corneal hasta las 250 µm (Morishige et
al. 2011). La región media y posterior del estroma se caracteriza por una organización de fibras
de colágeno que se distribuyen de manera paralela a la superficie posterior en dos direcciones
principales, nasal-temporal y superior-inferior (Benoit et al. 2016). Esta organización que
mantienen las fibras de colágeno conlleva que la parte anterior del estroma posea un mayor
módulo de elasticidad que las regiones media y posterior (Quantock et al. 2015).
La hipótesis de que SMILE preserva la biomecánica corneal en mayor medida que
LASIK posee un notable fundamento teórico si consideramos que: (1) el estroma anterior posee
una mayor rigidez; (2) el lentículo se talla a partir de una profundidad mayor a las 100 m de la
superficie corneal; (3) el lentículo se extrae a través de una micro-incisión de 2 mm por lo que
se secciona un considerable número menor de fibras en comparación a la creación de un flap.
No obstante, esta hipótesis, más allá de los modelos matemáticos y biomecánicos (Reinstein et
al. 2013; Sinha Roy et al. 2014), no ha demostrado consenso en sus evidencias clínicas. De
hecho, una de las principales preocupaciones por la cual la biomecánica corneal es de gran
importancia en el campo de la cirugía refractiva, además de su relación con los resultados
refractivos (Roy & Dupps 2009), es su papel en el desarrollo de ectasias corneales (Klein et al.
2006). Y a día de hoy, córneas sospechosas de queratocono subclínico desde el punto de vista
topográfico para las cuales la cirugía LASIK está contraindicada, han terminado desarrollando
una ectasia corneal al no asumir un criterio clínico conservador y aplicar una cirugía SMILE
(Randleman 2016). Por lo que los criterios clínicos de screening preoperatorio deben ser tan
rigurosos como los que hemos aprendido de nuestra experiencia con LASIK.
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
29
1.4. Evaluación clínica de la biomecánica corneal.
1.4.1. Instrumentos clínicos para la medida de la biomecánica
corneal.
Pese al creciente interés en la biomecánica corneal, tan solo se encuentran disponibles
en la actualidad dos instrumentos enfocados a su medida clínica. El primero de ellos, Ocular
Response Analyzer (ORA) (Reichert Inc. USA), apareció en el año 2005 con el objetivo de
realizar una medida de la presión intraocular (PIO) que estuviese menos afectada por el espesor
y las propiedades de la córnea en comparación con otros tonómetros (Glass et al. 2008). El
funcionamiento de este instrumento es similar al de un tonómetro de aire con una duración de
pulso de unos 20 ms. La presión ejercida por el pulso de aire aplana la córnea, la cual pasa a
tener una forma cóncava en el momento de máxima presión, volviendo a su posición inicial tras
el cese del pulso. Durante el movimiento de la córnea con el pulso, un haz de luz infrarrojo
incide lateralmente sobre la misma de tal manera que cuando la córnea se aplana, un
fotodetector situado en la posición opuesta recibe el flujo máximo de fotones, reconociendo de
esta forma la presión necesaria para alcanzar la aplanación (Figura 3). Puesto que la córnea pasa
dos veces por el estado de aplanación, una primera con el incremento de la presión y otra
cuando vuelve a su posición original, el instrumento captura las presiones ejercidas en el
momento de ambas aplanaciones (Fernández & Martínez 2015).
Figura 3. Diagrama que muestra las señales máximas alcanzadas por el receptor (línea roja) en la primera
______________________________________________________________________________________________
30
y segunda aplanación frente a la curva de presión del pulso de aire (línea verde).
La diferencia entre las presiones recibe el nombre de histéresis corneal (del inglés
Corneal Hysteresis, CH), mientras que una segunda variable denominada factor de resistencia
corneal (del inglés Corneal Resistance Factor, CRF) proviene de una función lineal P1-kP2,
donde k es una constante determinada a partir de un análisis empírico de la relación entre
presiones y espesor corneal (Piñero & Alcón 2015).
El segundo de los instrumentos es el Corvis ST (Oculus, Wetzlar, Germany) cuyos
primeros resultados clínicos fueron presentados en el año 2011 (Hon & Lam 2013). Su
funcionamiento se basa también en la deformación de la córnea a través de un pulso de aire pero
se captura a través de una cámara Scheimplflug de alta velocidad (4330 imágenes por segundo)
una sección horizontal de la córnea (Hon & Lam 2013). De esta forma, se obtiene un video
durante los 30 ms que dura el pulso de aire, pasando la córnea por tres estados: de primera
aplanación (A1), máxima concavidad (del inglés Highest Concavity, HC) y segunda aplanación
(A2). La principal ventaja de este sistema frente al ORA es que en todo momento visualizamos
la dinámica de la córnea y no solo capturamos los puntos de presión en los que se producen las
aplanaciones por lo cual el número de parámetros que podemos inferir a partir de las imágenes
es considerablemente mayor.
Figura 4. Fotogramas del video capturado por Corvis ST durante la fase de resistencia de la córnea al pulso de aire (izquierda) y la fase de recuperación tras el cese (derecha). Sobre la imagen se han dibujado en amarillo algunos de los parámetros inferidos durante la primera aplanación, máxima concavidad y segunda aplanación.
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
31
En la literatura científica, se recogen multitud de parámetros inferidos por el software,
aunque en este apartado tan solo vamos a hacer referencia a algunos de los más utilizados:
Tiempos de aplanación: El tiempo en el que se alcanzan las aplanaciones A1 y A2. Nos
referiremos a estas variables como AT1, y AT2.
Velocidad de aplanación: La velocidad de la córnea durante A1 y A2 (AV1 y AV2).
Longitud de aplanación: Longitud horizontal de la aplanación (AL1 y AL2)(Figura 4,
parámetros 1 y 5).
Amplitud de deformación: El desplazamiento que se produce en el ápex desde la
posición original hasta la máxima concavidad (DA)(Figura 4, parámetro 2).
Radio de la máxima concavidad: El radio de una circunferencia ajustada a la córnea en
la máxima concavidad (Figura 4, parámetro 3).
Distancia entre picos: Distancia entre los picos más elevados en la máxima concavidad
(Figura 4, parámetro 4)(PD).
Presión intraocular: Presión ejercida por el pulso de aire cuando se alcanza A1 (IOP).
Espesor corneal central: Espesor corneal medido en el centro de la córnea antes de que
esta sea deformada (CCT).
Éstas son solo algunas de las variables inferidas por el software comercial, sin embargo
muchas otras no han sido descritas por su menor popularidad o porque se encuentran
disponibles solo con motivos de investigación en versiones del software enfocadas para tal
propósito. No obstante, es importante resaltar que muchas de las variables anteriormente
descritas han sido cuestionadas por su baja repetibilidad como AV1, AV2, AL1, AL2 y PD
(Hon & Lam 2013; Nemeth et al. 2013; Chen et al. 2014).
1.4.2. Medida clínica de biomecánica corneal tras cirugía refractiva.
En los últimos años ha habido un incremento del interés en la investigación clínica de la
biomecánica corneal en SMILE, tanto en referencia a variaciones dentro de la propia técnica,
como en comparativa con otras técnicas que teóricamente deberían preservar en menor medida
la integridad corneal. La mayor parte de estas investigaciones han sido llevadas a cabo con el
instrumento ORA como muestran 12 de las 16 referencias consultadas incluidas en la Tabla 5.
De entre las conclusiones principales, se encuentra una baja evidencia de que SMILE afecte en
menor medida a la biomecánica corneal con respecto a otras técnicas, aunque algunos autores
apuntan a particularidades como dependencia del error refractivo, profundidad del lentículo o
tamaño de la incisión. En torno al instrumento Corvis ST, tan solo 5 de las 16 referencias
consultadas incluyen medidas con este instrumento, las cuales apuntan de igual forma que el
ORA a la falta de evidencia clínica de mayor preservación de la integridad corneal y a
diferencias en torno a variaciones en la técnica como puede ser la profundidad del lentículo.
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32
Tabla 5. Estudios que analizan la biomecánica corneal en SMILE, tanto en relación a variaciones de la
técnica como en comparativa con otras técnicas de cirugía refractiva.
Autor Instrumentos Técnicas Conclusión
(Pedersen et al. 2014) ORA y CORVIS FS-LASIK, FLEX, SMILE Sin diferencias entre técnicas
(Shen et al. 2014) CORVIS SMILE
Diferencias pre/post debidas a la
extracción del lentículo y no al
tallado del mismo.
(Leccisotti et al. 2016) CORVIS LASIK Diferencias tras el tallado del
lentículo sin la retirada del mismo.
(Wang et al. 2014) ORA FS-LASIK, SMILE Diferencias para miopías mayores
a 6D a favor de SMILE
(Sefat et al. 2016) CORVIS FS-LASIK, SMILE Sin diferencias entre técnicas
(Y Shen et al. 2014) CORVIS FS-LASIK, LASEK,
SMILE
Sin diferencias entre SMILE con
respecto al resto de técnicas
(El-Massry et al. 2015) ORA SMILE Menor afectación biomecánica a
160 m que a 100 m
(Agca, Ozgurhan,
Demirok, et al. 2014) ORA SMILE, FS-LASIK Sin diferencias entre técnicas
(Osman et al. 2016) ORA SMILE, FS-LASIK Mayor afectación en FS-LASIK
(Wu et al. 2014) ORA SMILE, FS-LASIK Mayor afectación en FS-LASIK
(Wang et al. 2016) ORA SMILE, FS-LASIK Mayor afectación en FS-LASIK
(He et al. 2016) CORVIS SMILE Menor afectación biomecánica a
160 m que a 100 m
(Kamiya et al. 2014) ORA SMILE, FLEX La realización del flap no provoca
diferencias entre técnicas
(Zhang et al. 2016) ORA SMILE, FS-LASIK WF* Sin diferencias entre técnicas
(Z. Wu et al. 2016) ORA SMILE
Mayor tamaño de la incisión
provoca mayor variación en las
variables
(Yıldırım et al. 2016) ORA SMILE; PRK Smile induce mayores cambios en
las variables
(Chen et al. 2016) ORA SMILE; LASEK Smile induce menores cambios en
las variables
*FS-LASIK WF: Técnicas LASIK con flap por femtosegundo y láser excimer guiado por frente de onda.
1.5. Justificación y objetivos.
Durante esta introducción hemos presentado la técnica de cirugía refractiva SMILE
junto con algunas controversias actuales. Podemos afirmar, como ya expusimos en el apartado
1.3.3, que la técnica SMILE es en términos generales tan segura, eficaz y predecible como la
técnica LASIK. No obstante, es importante resaltar que la cirugía SMILE podría considerarse
más cirujano-dependiente por incluir dentro del procedimiento la disección y extracción del
lentículo, donde la experiencia del cirujano podría influir en los resultados. El primero de los
objetivos de la presente Tesis doctoral es:
1. Analizar, en función del error refractivo tratado, los resultados de eficacia, seguridad y
predictibilidad de la técnica SMILE para los primeros casos llevados a cabo por un
cirujano con experiencia en cirugía refractiva, pero no experimentado en la técnica.
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
33
Muchas de las hipótesis surgidas en relación a SMILE, como la menor inducción de
sequedad ocular gracias a la disección de un menor número de fibras nerviosas corneales, se
encuentran clínicamente demostradas. No obstante, la controversia más importante en la
actualidad en relación a la técnica gira en torno a la preservación de la biomecánica corneal.
Pese a que existen simulaciones basadas en modelos matemáticos y biomecánicos como
relatamos en el apartado 1.3.5 que anuncian una mayor preservación de la biomecánica corneal
en SMILE que en LASIK, esta hipótesis no ha llegado a ser confirmada por la investigación
clínica, posiblemente debido a la falta de instrumentos fiables que permitan medir, de manera
aislada, los cambios producidos en la rigidez de la córnea debido a procedimientos de cirugía
refractiva láser corneal. La aparición de nuevas tecnologías, como el sistema Corvis ST, abre
nuevas posibilidades dentro de la investigación clínica relacionada con la biomecánica corneal
dentro la cirugía refractiva laser. Esta Tesis doctoral abarca otros tres objetivos principales
relacionados con el instrumento Corvis ST y la biomecánica corneal tras SMILE:
2. Evaluar los cambios en los parámetros más reproducibles del Corvis ST en función del
error refractivo tratado y analizar las variaciones de estos parámetros en función del
espesor corneal retirado.
3. Examinar los nuevos parámetros introducidos en la versión del software 1.3r1469
(Septiembre, 2016), evaluando como cambian tras SMILE y la dependencia de estos
parámetros frente a variables de confusión como el espesor corneal.
4. Presentar una nueva hipótesis sobre la densitometría dinámica y su posible relación
con la biomecánica e hidratación corneal y, por consiguiente, su potencial aplicación
para la evaluación de los cambios biomecánicos tras SMILE.
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1.6. Estructura de la Tesis.
Esta Tesis ha sido llevada a cabo mediante la compilación de artículos científicos. Cada
uno de estos artículos posee una estructura de Introducción, Métodos, Resultados y Discusión
que permite su compresión de manera individual. No obstante, los tres componen un solo
trabajo con un claro hilo argumental.
La Tesis se estructura en 4 Capítulos:
1. Introducción General.
2. Publicaciones.
2.1. Short-term outcomes of Small Incision Lenticule Extraction (SMILE) for low,
medium and high myopia.
2.2. Corneal thickness after SMILE affects Scheimpflug-based Dynamic
Tonometry.
2.3. New parameters for evaluating corneal biomechanics and intraocular pressure
after SMILE by Scheimpflug-Based Dynamic Tonometry.
3. Discusión de los resultados.
4. Conclusiones.
El contenido principal de la Tesis se encuentra recogido en el Capítulo 2 que incluye 3 artículos
publicados por revistas de prestigio internacional.
El primer artículo se titula “Short-term outcomes of Small Incision Lenticule Extraction
(SMILE) for low, medium and high myopia” (Fernández, Valero, et al. 2016). Los resultados
preliminares se presentaron en el XXIV Congreso OPTOM (Hueso et al. 2016) y,
posteriormente, este artículo se ha publicado en la revista “European Journal of
Ophthalmology”. Esta revista está soportada por Thomson Reuters en el Science Citation Index
(SCI). En el año 2015 su factor de impacto ha sido de 1,007, ocupando una posición relativa de
46/56 (Q4) en la categoría “Ophthalmology” del Journal Citation Rank. Esta revista publica
artículos clínicos originales de revisión por pares que muestren observaciones clínicas e
investigaciones de laboratorio con relevancia clínica, enfocada a nuevas técnicas de diagnóstico
y quirúrgicas, actualizaciones en terapias e instrumentos, resultados de ensayos clínicos y
hallazgos de investigación. Todos los artículos de esta revista se han sometido a una rigurosa
revisión por pares, basado en el cribado inicial y arbitraje de doble ciego de dos evaluadores
anónimos internacionales.
En este primer artículo se evalúan los resultados de seguridad, eficacia y predictibilidad de la
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
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técnica SMILE para los primeros 71 casos llevados a cabo por el autor de esta Tesis doctoral.
Estos resultados son de gran importancia para cualquier cirujano que se inicia en una nueva
técnica de cirugía refractiva. Pese a tener experiencia en otro tipo de cirugías refractivas
mediante láser, es importante conocer si los primeros resultados pueden verse afectados por la
experiencia del cirujano. Además, este trabajo se diferencia principalmente de otros similares en
que el análisis se lleva a cabo en función del error refractivo, lo cual aporta un valor adicional al
conocer cuáles deben ser las características refractivas de los pacientes durante la curva de
aprendizaje.
El segundo artículo se titula “Corneal thickness after SMILE affects Scheimpflug-based
Dynamic Tonometry” (Fernández, Rodríguez-Vallejo, Martínez, Tauste & Piñero 2016). Los
resultados preliminaries se presentaron en el XXXIV Congress of the ESCRS (Fernandez et al.
2016) y, posteriormente, este artículo se ha publicado en la revista “Journal of Refractive
Surgery”. Esta revista está soportada por Thomson Reuters en el Science Citation Index (SCI).
En el año 2015 su factor de impacto ha sido de 3,314, ocupando una posición relativa de 7/56
(Q1) en la categoría “Ophthalmology” del Journal Citation Rank. Esta revista publica artículos
de investigación, revisiones y evaluación de procedimientos de cirugía refractiva. Todos los
artículos de esta revista se han sometido a una rigurosa revisión por pares, basado en el cribado
inicial y arbitraje de doble ciego de dos evaluadores anónimos internacionales.
En este segundo artículo se analiza la variación de los parámetros más repetibles del sistema
Corvis ST frente al espesor corneal eliminado con la extracción del lentículo. Una de las
principales limitaciones de los instrumentos de medida clínica de la biomecánica corneal es la
gran influencia de variables de confusión como la presión intraocular o el espesor corneal. En
este trabajo, mediante la inclusión de datos preoperatorios y posoperatorios, se asume que la
presión intraocular no influye en la medida mientras que se analiza el impacto del espesor
corneal. A partir de este análisis se proponen soluciones para la corrección de los parámetros del
Corvis ST con el fin de minimizar el impacto de la variación de espesor corneal.
El tercer artículo se titula “New parameters for evaluating corneal biomechanics and
intraocular pressure after SMILE by Scheimpflug-Based Dynamic Tonometry.” (Fernández,
Rodríguez-Vallejo, Martínez, Tauste, Salvestrini, et al. 2016). Este artículo ha sido aceptado en
la revista “Journal of Cataract and Refractive Surgery”, estando aún pendiente de publicación.
Esta revista está soportada por Thomson Reuters en el Science Citation Index (SCI). En el año
2015 su factor de impacto ha sido de 3,020, ocupando una posición relativa de 12/56 (Q1) en la
categoría “Ophthalmology” del Journal Citation Rank. Esta revista publica artículos de
investigación, revisiones y evaluación de procedimientos de cirugía refractiva. Todos los
artículos de esta revista se han sometido a una rigurosa revisión por pares, basado en el cribado
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36
inicial y arbitraje de doble ciego de dos evaluadores anónimos internacionales.
Este tercer artículo supone una continuación del artículo anterior. Se incluyen nuevos
parámetros de biomecánica corneal añadidos en una importante actualización del software
llevada a cabo en Septiembre de 2016. Se analiza si estos nuevos parámetros se encuentran
sometidos a las mismas limitaciones que los descritos en el trabajo anterior. Además se
propone, por primera vez en investigación clínica en el campo de la oftalmología, la medida de
la densitometría corneal dinámica con el planteamiento de nuevas hipótesis que podrían
relacionar este parámetro con la biomecánica corneal y con la hidratación de la córnea.
En el Capítulo 3 se presenta una breve discusión acerca de los principales resultados mientras
que el Capítulo 4 muestra las conclusiones finales de la Tesis así como el cumplimiento de los
objetivos planteados. Para finalizar, se muestra la bibliografía general utilizada a lo largo de la
Tesis.
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
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CAPÍTULO 2 PUBLICACIONES
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
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Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
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2.1. Short-term outcomes of Small Incision Lenticule Extraction (SMILE)
for low, medium and high myopia.
Joaquín Fernández, MD;1 Almudena Valero, MD;1 Javier Martínez, OD;1 David P Piñero, PhD;2,3 Manuel Rodríguez-Vallejo, MSc *1
1Department of Ophthalmology (Qvision), Vithas Virgen del Mar Hospital, 04120, Almería, Spain 2Department of Optics, Pharmacology and Anatomy, University of Alicante, Alicante, Spain 3Department of Ophthalmology (OFTALMAR), Vithas Medimar International Hospital, Alicante, Spain *Corresponding author: manuelrodriguezid@qvision.es (Tel +34686500808)
2.1.1. Abstract
Purpose: To determine the safety, efficacy, and predictability of Small Incision Lenticule
Extraction (SMILE) at 6-month follow-up, depending on the level of the myopic refractive
error. The surgeries were performed by a novel surgeon in this technique.
Methods: Seventy-one subjects with a mean age of 31.86 ± 5.57 were included in this
retrospective observational study. Subjects were divided into 3 groups depending on the
preoperative Spherical Equivalent (SE): Low group from -1.00 D to -3.00 D, Medium from -
3.25 D to -5.00 D, and High from -5.25 D to -7.00 D. Manifest refraction, corrected (CDVA)
and uncorrected distance visual acuity (UDVA) were measured before surgery and at 6 months
after the treatment.
Results: In total, 1.4% of the eyes lost 1 line of CDVA after the procedure, whereas 95.8%
remained unchanged and 2.8% gained 1 line. A significant undercorrection (p=0.031) was found
in the High myopia group (median: -0.50 D), whereas Low and Medium groups remained near
to emmetropia. In terms of efficacy, no statistically significant inter-group differences for
postoperative UDVA (p = .282) were found. The vector analysis also showed undercorrection of
the preoperative cylinder, even though the standard deviations decreased from 0.9 D in the x
axis and 0.7 D in the y axis to 0.24 D and 0.27 D, respectively.
Conclusions: SMILE might be a safe, effective and predictable procedure even for non-
experienced surgeons. No differences in efficacy were found among myopia levels even though
undercorrections were found for SE and cylinder in high myopia.
Key Words: myopia, refractive surgery, small incision lenticule extraction, SMILE
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2.1.2. Introduction
Small-incision lenticule extraction (SMILE) has demonstrated similar or better visual and
refractive outcomes compared to traditional laser-assisted in situ keratomileusis (LASIK) in the
treatment of myopia, with the additional advantage of using only a laser system for the entire
procedure (Ang et al. 2012; Ganesh & Gupta 2014). Furthermore, some studies have shown
better results with this technique in optical quality than femtosecond LASIK (FS-LASIK), with
lower induction of higher-order aberrations (Gyldenkerne et al. 2015; Lin et al. 2014). However,
some authors suggest that SMILE has poorer visual recovery rates than LASIK (Vestergaard et
al. 2012), with considerable differences in uncorrected distance visual acuity (UDVA) achieved
between 1 day and 3 months (Hjortdal et al. 2012). It has been hypothesized that laser
parameters might affect visual recovery (Shah & Shah 2011; Kamiya et al. 2015), but other
recent studies have not found early postoperative interface scatter or delay in visual recovery
(Vestergaard et al. 2014) or have reported similar percentage for 20/20 or better at 1 day (89%)
in comparison to 1 month (91%) with SMILE (Reinstein, Carp, et al. 2014). Although longer
studies at 3, 6, and 12 months show that SMILE is a safe, effective, and predictable procedure
(Kim et al. 2014; Xu & Yang 2015), most are based on data from experienced SMILE surgeons
with personalized nomograms (Reinstein, Carp, et al. 2014) and either do not state whether the
surgeon had previous experience with SMILE before the study (Xu & Yang 2015) or analyze
the results independently of the degree of refractive error (Ivarsen et al. 2014; Li et al. 2014).
The aim of this study was to analyze the outcomes with SMILE at 6 months postoperatively
depending on the level of myopia for the first 71 consecutive patients of an inexperienced
surgeon.
2.1.3. Methods
Patients and examinations
One random eye of the first 71 consecutive patients treated with SMILE between September
2013 and January 2014 at Qvision (Department of Ophthalmology, Virgen del Mar Hospital)
were included in this retrospective observational study. Patients underwent a complete
preoperative eye examination including objective and subjective refraction performed by
optometrists, Goldmann intraocular pressure, aberrometry, pupil size, and corneal topography
with Orbscan II and Zywave systems (both from Bausch and Lomb, Rochester, NY, USA), slit-
lamp evaluation, and funduscopy. Postoperative visit at 6 months included UDVA, corrected
distance visual acuity (CDVA), manifest refraction, and slit-lamp examination to evaluate the
integrity of the anterior segment. Visual acuities (VAs) were measured with a LCD wall screen
in decimal notation scale and converted to Snellen for reporting in standardized graphs.
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Inclusion criteria were patients undergoing 6-month follow-up after the procedure with
preoperative spherical equivalent (SE) between -1 D and -7 D and astigmatism under 3.5 D,
stable myopia for at least 1 year before surgery, and CDVA of 20/25 or better. Exclusion criteria
were pregnancy at time of surgery or follow-up, a preoperative central corneal thickness of less
than 480 μm, an expected postoperative residual stromal bed of less than 250 μm, topographic
map compatible with subclinical keratoconus or other ectatic corneal disorder, and any other
ocular disease for which laser refractive surgery procedures are not indicated (Shetty et al.
2015). The procedure was explained to all the patients who signed the preoperative informed
consent, and the study complied with the tenets of the Declaration of Helsinki.
Surgical procedure
Optical principles and general description of the SMILE procedure have been widely described
(Reinstein, Archer, et al. 2014); however, some particular laser settings or surgical maneuvers
can vary depending on the surgeon. The particular laser settings and maneuvers for this study
are detailed below. Before suction, centration was accepted when the ring of the applanation
zone was concentric with the margin of the cone and near to the pupil center (Li et al. 2014).
Suction was then applied, and a slight rotation of the applanation cone was made to compensate
for cyclotorsion in cases of high astigmatism with markings, taking as reference the horizontal
lines seen through the microscope.
The photodisruptive procedure follows the next sequence: the laser creates the lower lenticular
interface from center to periphery; this is the lenticule diameter or optical zone, which was set to
6.5 mm. A transition zone with a side cut angle of 90° follows the optical zone cut for
intersecting the upper lenticular interface. The laser creates the cap of 7.6 mm of diameter, 1.1
mm larger than the optical zone, in such a way that the lenticule is confined below the cap. The
depth or cap thickness was set to 140 μm and the laser software computes the lenticule thickness
depending on the refractive error, but a minimum thickness of 15 μm was configured. Finally,
the incision at the extreme of the cap, 2 mm of width, is created with a side cut angle of 30° for
extracting the lenticule close to 12 o’clock position. A graphical description for understanding
each one of these parameters has been detailed by other authors (Bischoff & Strobrawa 2016).
Laser configuration parameters were as follows: repetition rate of 500 kHz, spot distance of 4.50
μm for the lenticule and 2 μm for its border, and pulse energy of level 30 in the software, which
corresponds to approximately 150 nJ (Vestergaard et al. 2014). The target refractive error
correction was directly inserted in the software without applying any nomogram. After laser
treatment, the patient was moved to the surgical microscope for the second part of the
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44
procedure, which involves the following: (1) delineating front and back lenticule surfaces; (2)
surface separation using the standard lamellar corneal surgical technique of moving the
instrument back and forth using a blunt circular tip (Femto Double-Ended instrument [G-
33954], Carl Zeiss Meditec AG, Jena, Germany) starting with the complete dissection of the
front cap and following with the dissection of the posterior lenticule surface; (3) lenticule
extraction with forceps (Lenticule Forceps [G-33961], Carl Zeiss Meditec AG); (4) corneal
surface pressure from center to periphery using a dry microspear and drying the incision with
the same. Finally, all patients received 2 drops of tobramycin (3 mg) and dexamethasone (1 mg)
combination at the end of the procedure.
The same surgeon (J.F.) performed all the SMILE treatments with the VisuMax femtosecond
laser system (Carl Zeiss Meditec AG). It is important to note that this sample corresponded with
the first consecutive SMILE cases of this surgeon, including results from the early phase of the
learning curve. All patients were treated with 2 drops of topical anesthesia (oxybuprocaine
hydrochloride 0.4%) at 5 minutes and 2 further drops 1 minute before surgery. In patients
requiring astigmatism correction over 1.50 D, corneal reference marks were made before
surgery at the 3-o’clock and 9-o’clock meridians with the patient standing up.
Statistical analysis
Even though both eyes from each patient were operated and measured before SMILE surgery
and at 6 months, a random eye per subject was included in the statistical analysis because of the
high concordance shown in the preoperative SE between eyes (ICC 0.92, p<0.001; 95%
confidence interval 0.87, 0.95) (Karakosta et al. 2012). If one of both eyes of the patient
presented a complication, the patient was excluded from the randomization and the contralateral
eye was included in the statistical analysis, but the complication was included in the safety
section. The randomization was performed with a MATLAB function (The Mathworks Inc.,
Natick, MA, USA) that filtered randomly the data of one eye for each patient. Eyes were
divided into 3 groups depending on the preoperative SE. Thirty eyes (42.3%) were included in
the low group, from -1.00 D to -3.00 D, 31 (43.7%) in the medium, from -3.25 D to -5.00 D,
and 10 (14.1%) in the high, from -5.25 D to -7.00 D. Decimal VAs were converted to logMAR
for assessing the differences between groups (Yu & Afifi 2009), and were later reconverted to
Snellen for reporting results to follow the standard graphs reporting results (Waring et al. 2011).
Visual acuity of 0.9 decimal was considered as 20/25 for plotting the standard graphs (Waring
et al. 2011), but its value was maintained after conversion to logMAR for statistical purposes.
Nonparametric statistical methods were used due to nonnormal distribution of study variables.
The Wilcoxon signed rank test was used to evaluate the differences between preoperative
Cirugía refractiva láser corneal SMILE. Resultados visuales y biomecánica corneal en miopías bajas, medias y altas
45
CDVA and postoperative UDVA. A Kruskal-Wallis H test was run to determine if there were
differences in some groups. Pairwise comparisons were done with a Bonferroni correction for
multiple comparisons. Statistical analyses were performed using SPSS (v20; SPSS Inc.,
Chicago, IL, USA), and significance was set at p<0.05. Standard graphics (Eydelman et al.
2006; Waring et al. 2011) were generated using Microsoft Excel 2010 (Microsoft Corporation,
Redmond, WA, USA) and our own MATLAB library was used for vector analyses.
2.1.4. Results
Seventy-one consecutive myopic eyes of 71 patients, mean age 31.86 ± 5.57 SD (range 21-43
years), were included in the sample. Table I provides the preoperative data of these patients
stratified depending on their refractive error level.
Table 1. Preoperative descriptive analysis of the sample by refractive error.
Parameters
Low (n=31) Medium (n=30) High (n=10)
Mean (SD) Median [Range]
Mean (SD) Median [Range]
Mean (SD) Median [Range]
Age 32.20 (5.25) 33.50 [25,43] 31.58 (5.64) 31.00 [22,43] 28.70 (5.38) 28.00 [21,36]
UDVA (logMAR)
0.72 (0.26) 0.7 [ 0.3, 1.3] 1.04 (0.18) 1.0 [ 0.7, 1.3] 1.33 (0.26) 1.3 [ 1.0, 2.0]
CDVA (logMAR)
-0.02 (0.04) 0.0 [-0.1, 0.0] 0.02 (0.03) 0.0 [-0.1, 0.0] 0.00 (0.05) 0.0 [-0.1, 0.0]
Manifest SE (D)
-2.07 (0.58) -2.00 [-3.00,-1.00] -3.86 (0.57) -3.75 [-5.00,-3.25] -5.86 (0.58) -5.81 [-6.88,-5.25]
Safety
In total, 95.8% (68 eyes) had unchanged CDVA, 1.4% (1 eye) lost 1 line, and 2.8% (2 eyes)
gained 1 line. The eye that lost 1 line belonged to the low myopic group, whereas eyes that
gained 1 line belonged to the high myopic group. There were no eyes with CDVA worse than
20/40 for the subgroup of eyes with CDVA of 20/20 or better preoperatively. No eye showed an
increase in manifest refractive astigmatism of 2.00 D over preoperative refraction. One eye had
a suction
loss during the surgical procedure, which was not included in the sample for reporting refractive
results. The suction happened during the lower lenticular interface creation and SMILE was
reapplied on the same day. This eye posteriorly developed epithelial ingrowth, corneal folds,
and irregular astigmatism that were solved with photorefractive keratectomy (PRK), achieving
UDVA of 20/25 and CDVA of 20/20.
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46
Fig. 2. Predictability for all eyes, and for eyes from the low, middle, and high spherical equivalent (SE) groups.
Predictability
The slope (0.9475) of the linear regression model (p<0.001) relating achieved and intended SE
confirmed the slight trend to undercorrection, especially for high myopic eyes (Fig. 1). More
detailed information about predictability is shown in Figure 2, where it can be seen that more
than
half of the subjects (52%) were close to emmetropia, and 26% achieved an SE between -0.50 D
and -0.14 D. The undercorrection was more evident in the high myopic group, with 70% of eyes
achieving SE between -1.00 D and -0.14 D.
Indeed, the median SE was 0 D for low and medium myopic groups and -0.50 D for the high
myopic group; the difference was statistically significant, p = 0.031. We also found statistically
significant differences in postoperative SE between the medium (40.95) and high myopic
groups (22.20) (p = 0.026), but not between the low (35.48) and high or medium myopic groups
(Tab. II). The percentages of eyes with SE within ±0.50 D were 87%, 92%, 80%, and 86% for
low, medium, and high myopic groups and the total sample, respectively, and 97%, 98%, 100%,
and 97% of eyes were within ±1.00 D.
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Fig. 1. Linear regression model for predictability. The scatterplot shows undercorrection with the increase in attempted spherical equivalent.
Table 2. Postoperative analysis of eyes from the Low, Medium and High myopic refractive groups and evaluation of median differences between preoperative CDVA and postoperative UDVA.
Low (n=31) Medium (n=30) High (n=10)
Parameter Median [Range] Median [Range] Median [Range] p-value*
UDVA (logMAR) 0.0 [-0.1,0.3] 0.0 [-0.1,0.2] 0.0 [ 0.0,0.1] .282 CDVA (logMAR) 0.0 [-0.1,0.0] 0.0 [-0.1,0.0] 0.0 [-0.1,0.0] .232 Manifest SE (D) 0.00 [-1.63, 0.25] 0.00 [-1.13,0.50] -0.50 [-1.00,0.00] .031
Pre CDVA –Pos UDVA 0 [0, 0.5] 0 [-0.1, 0.3] 0 [-0.1, 0.4] .099
* Kruskal-Wallis H test
Efficacy
A postoperative UDVA of 20/20 or better was achieved by 67% and 74% of eyes in the low and
medium myopic groups, respectively. However, the percentage for this level of UDVA for the
high myopic group was 50%. We found that 100% of eyes in the high myopic group had UDVA
of 20/25, whereas for this level the percentage was 97% for the low and medium myopic groups
(Fig. 3). Median was close to 20/20 for all groups (Tab. II), and no statistically significant
differences were found among them, p = 0.282. Median differences in CDVA between groups
were not statistically significant, p = 0.232 (Tab. II).
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Fig. 3. Cumulative percentage of eyes with different post-small incision lenticule extraction levels of uncorrected distance visual acuity (UDVA), by refractive error group.
The comparison of results from Figure 3 (UDVA) with the percentage of subjects with
preoperative CDVA of 20/20 or better (Fig. 4) revealed that 17% of eyes achieved 1 line of
UDVA less than the preoperative VA obtained with spectacles (CDVA). This was more
remarkable in the low myopic group, where this percentage decreased from 97% to 67% (30%
of decrease), whereas in the medium and high myopic groups this percentage only decreased
from 81% to 74% (7%) and from 60% to 50% (10%), respectively. Of the 71 operated eyes, a
decline from preoperative CDVA to postoperative UDVA was found in 21 eyes, 4 eyes
presented improvement, and 46 eyes maintained the same VA. Even though the median was
20/20 for preoperative CDVA and postoperative UDVA, the Wilcoxon signed rank test showed
statistically significant differences among both VA values, p<0.0005. The mean and standard
deviation was -0.01 ± 0.04 for preoperative CDVA and 0.03 ± 0.06 for postoperative UDVA,
the difference being less than 1 line of VA. Differences in postoperative UDVA minus
preoperative CDVA among low, medium, and high myopic groups were not statistically
significant, p = 0.099 (Tab. II).
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Fig. 4. Cumulative percentage of eyes with different pre-small-incision lenticule extraction levels of corrected distance visual acuity (CDVA), by refractive error group.
Vector analyses
Only eyes with preoperative astigmatism greater than zero were included in the vector analysis
(n = 46). Figure 5A shows that the centroid coordinates (x, y) were near to 0 (-0.13, -0.01) for
the intended refractive cylinder, and the standard deviation (radii of the ellipse) was higher in
the horizontal axis SDx = 0.9 D than in the vertical SDy = 0.7 D. Therefore, the sample was
evenly distributed between with the rule (WTR) and against the rule (ATR) astigmatisms, with
less incidence of oblique astigmatism. Figure 5B shows the error vector or manifest cylinder
after 6 months, showing how centroid coordinates were slightly close to 0 (-0.1, -0.01), although
standard
deviation decreased considerably to SDx = 0.24 D and SDy = 0.27 D. Furthermore, scatter at
the left side of Figure 5B appeared to be greater than on the right side, suggesting an
undercorrection of WTR or overcorrection of ATR. The normalized error vector in Figure 5C
and treatment error vector in Figure 5D, with overcorrections on the left side and
undercorrections on the right side, showed that an undercorrection was generally presented for
the cylinder.
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Fig. 5. Each radial step represents an increase of 0.50 D from the center. (A) Intended refractive correction, which is the preoperative positive cylinder. (B) Error vector represents the residual refractive cylinder or postsurgery cylinder. (C) Normalized error vector and (D) treatment error vector represent the overcorrection at the right side of the vertical axis. Some computed points appear overlapped for low dioptric values of B, C, and D.
2.1.5. Discussion
We present the early outcomes of an inexperienced SMILE surgeon with previous experience in
other laser refractive surgery techniques. One random eye from the first consecutive 71 subjects
was included and analyzed depending on the refractive error level at 6-month follow-up.
Suction loss is one of the complications that have been reported with SMILE (Wong et al.
2014), but we only found 1 case, corresponding to the consecutive second surgery. Other
complications of SMILE have been reported, such as incomplete femtosecond laser cutting
(Reinstein, Carp, et al. 2014), opaque bubble layer (Wang et al. 2014), infiltrates/keratitis or
interface inflammation (Zhao et al. 2015), abrasion at the incision, tears at the incision, cap
perforation, haze, dry surface,
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epithelial islands at the incision, and fiber at the interface (Piñero-Llorens et al. 2016).
However, we only found 1 eye with epithelial ingrowth and corneal folds. In terms of
preoperative and postoperative CDVA, we found that SMILE was a safe procedure with only
1.4% of eyes losing 1 line of VA corresponding to the low myopic group. These results are
slightly better than those reported by other authors (Reinstein, Carp, et al. 2014; Shah et al.
2011). As the percentage of eyes gaining 1 line of VA increased with the refractive error level,
this improvement of postoperative CDVA may be due to the change in retinal image
magnification after surgery compared to the use of spectacles in high myopic eyes (Vestergaard
et al. 2014; Xu & Yang 2015).
The first predictability results for SMILE at 6 months were reported by Shah et al (Shah et al.
2011). They found a mean SE of +0.03 ± 0.30 D, with 91% of subjects within ±0.50 D and
100% within ±1.00 D. They reported that refractive stability was achieved within 1 month,
suggesting that predictability of SMILE would be similar in studies with longer periods of
follow-up. Subsequent studies at 3, 6, and 12 months have found that the percentage of subjects
within ±0.50 D ranged from 77% to 100%, and within ±1.00 D from 94% to 100% depending
on the study (Shah & Shah 2011; Hjortdal et al. 2012). Our results are consistent with those
reported in previous studies, with 86% of eyes with SE within ±0.50 D and 96% within ±1.00
D. Furthermore, we found a poorer predictability for refractive errors between -5.25 D and -7 D,
with a median of -0.5 D for the postoperative SE in this group, while median SE was plano for
low and medium refractive error groups. The undercorrection was associated with an increased
refractive error, in which is consistent with the slope of the attempted versus achieved SE linear
regression equation. This finding has been reported in other studies (Kamiya et al. 2012; Kim et
al. 2014).
Some concerns over the cutting accuracy of the VisuMax or difficulties handling thinner
lenticules have been pointed out (Reinstein, Carp, et al. 2014). We usually increase the diameter
of the optical zone for myopias under -1 D in order to increase the lenticule thickness to around
50 μm, but this was not done in this study because all patients were over -1 D of SE. Despite the
thinner lenticule in the low myopic group, no problems occurred in handling or extracting it.
Our efficacy results for the low myopic group contrast with those previously reported by
Reinstein et al (Reinstein, Carp, et al. 2014), who found, with their own nomogram, that 97% of
eyes achieved UDVA of 20/20 at 3 months after SMILE. In our sample, only 67% achieved a
UDVA of 20/20.
It is important to note that these differences might be due to the fact that the Reinstein et al
cohort had a cumulative percentage of preoperative CDVA (75%) of 20/16. This is considerably
higher than ours (23%); therefore it is also understandable that the percentage of subjects with
UDVA of 20/20 would be higher in their study because the preoperative CDVA was better.
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The median change in VA from preoperative CDVA to postoperative UDVA was significant;
nevertheless, it was less than 1 line of VA. Furthermore, no statistically significant differences
in median VA change among the 3 groups were found, even though the percentage of subjects
at 20/20 level decreased in a higher percentage (30%) in the low myopic group than in the
medium (7%) and high myopic (10%) groups. This shows that SMILE might be as effective for
low myopias as it is for medium and high myopias. It is important to note that 2 patients of the
high myopic group and one of the low myopic group were treated successfully with PRK after
this follow-up because they returned with complaints about their UDVA.
However, some other patients of the high myopic group who presented UDVA less than 20/20
were not retreated with PRK if they were satisfied with their binocular vision. Ivarsen and
Hjortdal (Ivarsen & Hjortdal 2014) reported a significant undercorrection of astigmatism as the
intended refractive correction of the cylinder increased, which was similar to or better than
FSLASIK. This undercorrection has been also reported by Kunert et al (Kunert et al. 2013),
who found the centroid moved to the right of the vertical in the normalized error vector. In our
study, we found that the correction of the cylinder is predictable with SMILE because the
standard deviation was reduced from 0.9 D and 0.7 D to 0.24 D and 0.27 D. However, as the
foregoing authors described in their studies, an undercorrection was shown in the normalized
error vector since the data are predominantly moved to the right of the vertical (Eydelman et al.
2006).
Our research may have some limitations. We have only included myopic refractive SE
refractions from -1 D to -7 D; however, SMILE has been awarded European conformity up to -
10 D at the time of our study. Therefore, for comparison purposes in future studies that include
myopias up to -10 D, the creation of a new level of very high myopia from -7.25 D to -10 D
would be recommended. Furthermore, a poorly balanced sample was used, with only 10 eyes in
the high myopia group, whereas the low and medium myopic groups had 30 and 31 eyes,
respectively. A brief analysis of astigmatism has been included in terms of magnitude;
nevertheless, it is important to note that studies centered on astigmatism results should be
performed in terms of magnitude and angle of error (Zhang et al. 2016). About cap thickness, it
is important to note that
it was set to 140 μm, which can vary between authors, but Güell et al (Güell et al. 2015)
reported no differences in refractive result for lenticule thicknesses of 130, 140, 150, and 160
μm.
In summary, short-term outcomes of the SMILE technique for a novel surgeon were as safe,
effective, and predictable as those previously reported in the literature for more experienced
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surgeons. Furthermore, no differences in the effectiveness of the procedure were found among
low, medium, or high myopias. Future studies should include groups with myopias between -
7.25 D and -10.00 D and the development of nomograms that improve the results obtained in
this and
previous studies.
2.1.6. Disclosures
Financial support: Supported by the Sociedad Española de Cirugía Implanto Refractiva
(SECOIR) PUBLIbeCA 2014 grant.
Conflict of interest: Dr. Fernández is a consultant for Carl Zeiss Meditec (Jena, Germany). The
remaining authors have no financial or proprietary interest in the materials presented herein.
2.1.7. References
Ang, M., Tan, D. & Mehta, J.S., 2012. Small incision lenticule extraction (SMILE) versus laser in-situ keratomileusis (LASIK): study protocol for a randomized, non-inferiority trial. Trials, 13, p.75.
Bischoff, M. & Strobrawa, G., 2016. Femtosecond laser keratomes for Small Incision Lenticule Extraction (SMILE). In W. Sekundo, ed. Small Incision Lenticule Extraction (SMILE). Principles, Techniques, Complication Management, and Future Concepts. Springer, p. 8.
Eydelman, M.B. et al., 2006. Standardized analyses of correction of astigmatism by laser systems that reshape the cornea. Journal of refractive surgery (Thorofare, N.J. : 1995), 22(1), pp.81–95.
Ganesh, S. & Gupta, R., 2014. Comparison of visual and refractive outcomes following femtosecond laser-assisted lasik with smile in patients with myopia or myopic astigmatism. J Refract Surg., 30(9), pp.590–6.
Güell, J.L. et al., 2015. SMILE Procedures With Four Different Cap Thicknesses for the Correction of Myopia and Myopic Astigmatism. J Refract Surg., 31(9), pp.580–585.
Gyldenkerne, A., Ivarsen, A. & Hjortdal, J.Ø., 2015. Comparison of corneal shape changes and aberrations induced by FS-LASIK and SMILE for Myopia. J Refract Surg., 31(4), pp.160–165.
Hjortdal, J.Ø. et al., 2012. Predictors for the outcome of small-incision lenticule extraction for Myopia. J Refract Surg., 28(12), pp.865–71.
Ivarsen, A., Asp, S. & Hjortdal, J., 2014. Safety and complications of more than 1500 small-incision lenticule extraction procedures. Ophthalmology, 121(4), pp.822–828.
Ivarsen, A. & Hjortdal, J., 2014. Correction of myopic astigmatism with small incision lenticule extraction. J Refract Surg., 30(4), pp.240–7.
Kamiya, K. et al., 2012. Early clinical outcomes, including efficacy and endothelial cell loss, of refractive lenticule extraction using a 500 kHz femtosecond laser to correct myopia. J Cataract Refract Surg, 38(11), pp.1996–2002.
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Kamiya, K. et al., 2015. Effect of femtosecond laser setting on visual performance after small-incision lenticule extraction for myopia. Br J Ophthalmol, bjophthalm, p.Published Online First: 8 April 2015.
Karakosta, A. et al., 2012. Choice of analytic approach for eye-specific outcomes: one eye or two? American journal of ophthalmology, 153(3), p.571–579.e1.
Kim, J. et al., 2014. Efficacy, predictability, and safety of small incision lenticule extraction: 6-months prospective cohort study. BMC Ophthalmology, 14(1), p.117.
Kunert, K.S. et al., 2013. Vector analysis of myopic astigmatism corrected by femtosecond refractive lenticule extraction. J Cataract Refract Surg, 39(5), pp.759–769.
Li, M. et al., 2014. Mild decentration measured by a Scheimpflug camera and its impact on visual quality following SMILE in the early learning curve. Inves Opthal Vis Sci, 55(6), pp.3886–3892.
Lin, F., Xu, Y. & Yang, Y., 2014. Comparison of the visual results after SMILE and femtosecond laser-assisted LASIK for myopia. J Refract Surg., 30(4), pp.248–54.
Piñero-Llorens, D.P., Murueta-Goyena Larrañaga, A. & Hannekend, L., 2016. Visual outcomes and complications of small-incision lenticule extraction: a review. Expert Review of Ophthalmology, 11(1).
Reinstein, D., Carp, G.I., et al., 2014. Outcomes of small incision lenticule extraction (SMILE) in low myopia. J Refract Surg., 30(12), pp.812–818.
Reinstein, D., Archer, T.J. & Gobbe, M., 2014. Small Incision Lenticule Extraction (SMILE) history, fundamentals of a new refractive surgery technique and clinical outcomes. Eye and Vision, 1(1), p.3.
Shah, R. & Shah, S., 2011. Effect of scanning patterns on the results of femtosecond laser lenticule extraction refractive surgery. J Cataract Refract Surg, 37(9), pp.1636–1647.
Shah, R., Shah, S. & Sengupta, S., 2011. Results of small incision lenticule extraction: All-in-one femtosecond laser refractive surgery. J Cataract Refract Surg, 37(1), pp.127–137.
Shetty, R. et al., 2015. Association between corneal deformation and ease of lenticule separation from residual stroma in Small Incision Lenticule Extraction. Cornea, 34(9), pp.1067–71.
Vestergaard, A. et al., 2012. Small-incision lenticule extraction for moderate to high myopia: Predictability, safety, and patient satisfaction. J Cataract Refract Surg, 38(11), pp.2003–10.
Vestergaard, A.H. et al., 2014. Efficacy, safety, predictability, contrast sensitivity, and aberrations after femtosecond laser lenticule extraction. J Cataract Refract Surg, 40(3), pp.403–11.
Wang, Y. et al., 2014. Two millimeter micro incision lenticule extraction surgery with minimal invasion: a preliminary clinical report. Zhonghua Yan Ke Za Zhi., 50(9), pp.671–80.
Waring, G.O. et al., 2011. Standardized graphs and terms for refractive surgery results. J Refract Surg., 27(1), pp.7–9.
Wong, C.W. et al., 2014. Incidence and management of suction loss in refractive lenticule extraction. J Cataract Refract Surg, 40(12), pp.2002–2010.
Xu, Y. & Yang, Y., 2015. Small-Incision Lenticule Extraction for myopia: Results of a 12-month prospective study. Optom Vis Sci, 92(1), pp.123–131.
Yu, F. & Afifi, A., 2009. Descriptive statistics in ophthalmic research. American journal of ophthalmology, 147(3), pp.389–91.
Zhang, J., Wang, Y. & Chen, X., 2016. Comparison of moderate- to High-Astigmatism
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corrections using WaveFront – Guided Laser In Situ Keratomileusis and Small-Incision Lenticule Extraction. Cornea, 35(4), pp.523–530.
Zhao, J. et al., 2015. Diffuse lamellar keratitis after small-incision lenticule extraction. J Cataract Refract Surg, 41(2), pp.400–407.
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2.2. Corneal thickness after SMILE affects Scheimpflug-based Dynamic
Tonometry
Joaquín Fernández, MD;1 Manuel Rodríguez-Vallejo, MS;*1 Javier Martínez, OD;1 Ana Tauste, MS; 1 David P Piñero, PhD;2,3
1Department of Ophthalmology (Qvision), Vithas Virgen del Mar Hospital, 04120, Almería, Spain 2Department of Optics, Pharmacology and Anatomy, University of Alicante, Alicante, Spain 3Department of Ophthalmology (OFTALMAR), Vithas Medimar International Hospital, Alicante, Spain *Corresponding author: manuelrodriguezid@qvision.es (Tel +34686500808)
2.2.1. Abstract
Purpose: To evaluate the corneal biomechanical changes due to small incision lenticule
extraction (SMILE) measured by Scheimpflug-based dynamic tonometry and to assess the
impact of the corneal thickness.
Methods: Sixty-eight patients measured with the Corvis ST (Oculus Optikgeräte GmbH,
Wetzlar, Germany) preoperatively and 1 month after SMILE were included in this retrospective
observational study. Patients were divided into three groups depending on the preoperative
spherical equivalent: low from -1.00 to -3.00 diopters (D), medium from -3.25 to -5.00 D, and
high from -5.25 to -7.25 D. Changes in Corvis ST parameters due to the surgery were analyzed
and new indexes for correcting the impact of corneal thickness were proposed.
Results: First and second applanation times changed after SMILE (P < .0001) but no
differences were found in the comparison between these relative changes (P = .31). First
applanation time was correlated with central corneal thickness (r = 0.368, P = .002) but not
second applanation time (r = -0.149, P = .23). The change in first applanation time due to
SMILE was different among
myopic groups (P = .007) but equal when a new index that considers the removed central
corneal thickness was used for comparison (P = .31). Deformation amplitude was also increased
after SMILE (P < .0001), but after subtracting the removed corneal thickness from the
postoperative deformation amplitude the result was equal to the preoperative deformation
amplitude (P = .26).
Conclusions: SMILE produces significant changes in the Corvis ST parameters of time and
deformation amplitude, but these changes are mainly explained by the confounding variable of
corneal thickness.
Key Words: corneal biomechanics, SMILE, Corvis ST, corneal thickness, refractive surgery
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2.2.2. Introduction
Corneal biomechanics is of great importance in laser refractive surgery because it can affect the
prediction of clinical outcomes (Roy & Dupps 2009) and might be related to the development of
corneal ectasia after surgery (Randleman et al. 2008). Although it has still not been widely
incorporated in clinical practice for screening purposes, the fact that postoperative ectasia can
occur without apparent preoperative risk factors with current technology (Klein et al. 2006) has
led to a growing interest in new clinical methods for assessing corneal stiffness. Furthermore,
Reinstein et al. (Reinstein et al. 2013) hypothesized that the new technique small incision
lenticule extraction (SMILE) may better preserve stromal tensile strength compared to previous
laser techniques such as photorefractive keratectomy and LASIK because of the absence of a
flap and the fact that the stiffer anterior part of the cornea remains intact. Therefore, clinical
studies have
focused on comparing the cornea response after each of these procedures (Y Shen et al. 2014).
Agca et al. (Agca et al. 2014) used the Ocular Response Analyzer (Reichert, Inc., Buffalo, NY)
to measure the corneal hysteresis and corneal response factor parameters and did not obtain
significant differences between SMILE and femtosecond laser-assisted LASIK. Conversely,
Dou et al. (Dou et al. 2015) found that SMILE seemed to have less effect on corneal
biomechanics than LASEK in terms of per unit tissue removed and El-Massry et al. (El-Massry
et al. 2015) reported that postoperative corneal hysteresis and corneal response factor
parameters were dependent on the lenticule depth in patients who had SMILE.
A new instrument named Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany) provides
more parameters that might be related to corneal biomechanics, but comparison of techniques
with this new instrument remains controversial. Hassan et al. (Hassan et al. 2014) reported no
differences after photorefractive keratectomy and LASIK in comparison to preoperative data in
almost all of the Corvis ST parameters analyzed, but this is not in agreement with other
preoperative–postoperative studies using LASIK (Frings et al. 2015). Chen et al. (Chen et al.
2014) reported differences between photorefractive keratectomy and virgin eyes, but Pedersen
et al. (Pedersen et al. 2014) found no differences between control and LASIK, femtosecond
lenticule extraction, or SMILE groups for all parameters except AT1 deflection length. Shen et
al. (Shen et al. 2014) measured with the Corvis ST just after lenticule creation and later after
extraction, and discovered that Corvis ST parameters changed significantly only during
extraction.
The aims of the current study were to evaluate the biomechanical changes of the cornea after
SMILE and to analyze the impact that the removed corneal thickness may have on the most
repeatable Corvis ST parameters. New indexes that consider the removed corneal thickness
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have been proposed for future comparisons between refractive surgery techniques.
2.2.3. Methods
Patients
Patients operated on with the SMILE technique between January 2014 and January 2016 at
Qvision (Department of Ophthalmology, Virgen del Mar Hospital) were identified in this
retrospective observational study. The procedure was explained to all of the patients, who
signed the preoperative informed consent. Institutional review board approval was obtained and
the study complied with the tenets of the Declaration of Helsinki.
Inclusion criteria were myopic patients with spherical equivalent from -1.00 to -7.25 diopters
(D) and refractive astigmatism less than 3.00 D who were measured preoperatively and 1 month
after SMILE with the Corvis ST. Preoperative exclusion criteria were pregnancy at the time of
surgery or follow-up, a preoperative central corneal thickness of less than 480 μm, an expected
postoperative residual stromal bed of less than 250 μm, a topographic map compatible with
subclinical keratoconus or other ectatic corneal disorder, and any other ocular disease for which
laser refractive surgery procedures are not indicated (Shetty et al. 2015). Postoperative
exclusion criteria included intraocular pressure (IOP) greater than 19 mm Hg before or after
SMILE, central corneal thickness (CCT) greater than that before the surgery, postoperative
complications, and patients who had undergone a laser re-treatment. Measurements by the
Corvis ST with alert messages of “pressure profile” and “lost images,” which indicate poor
quality, were also excluded. However, other alerts such as “model deviation,” “lost points,” and
“alignment” were not discarded after consulting with the Corvis ST manufacturer about the
possible influence of these alerts on the results.
Surgical procedure
The same surgeon (JF) performed all SMILE treatments with the VisuMax femtosecond laser
system (Carl Zeiss Meditec AG, Jena, Germany). Two drops of topical anesthesia
(oxybuprocaine hydrochloride 0.4%) were instilled at 5 minutes and two additional drops at 1
minute before surgery. In patients requiring astigmatism correction greater than 1.50 D, corneal
reference marks were made before surgery at the 3- and 9-o’clock meridians with the patient
standing up.
The optical principles and general description of the SMILE procedure have been widely
described (Reinstein et al. 2014), but some particular laser settings or surgical maneuvers were
used. Before suction, centration was accepted when the ring of the applanation zone was
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concentric with the margin of the cone and near to the pupil center (Li et al. 2014). Suction was
then applied, and a slight rotation of the applanation cone was made to compensate for
cyclotorsion in cases of high astigmatism with markings, taking as reference the horizontal lines
seen through the microscope. The photodisruptive procedure occurs in the following sequence:
(1) posterior lenticule creation from periphery to center (optical zone of 6.5 mm); (2) transition
zone after the peripheral optical zone greater than 1 mm of the optical zone; (3) anterior
lenticule from center to periphery with a cap diameter of 7.6 mm and cap thickness of 140 μm;
and (4) peripheral incision of 2 mm with 30° of angle for posterior lenticule extraction at 70°
(Bischoff & Strobrawa 2016). In SMILE, the cap depth is theoretically constant across the
anterior surface of the lenticule and the depth of the posterior lenticule surface is established by
the software depending on the attempted refractive correction.
Laser configuration parameters were: repetition rate of 500 kHz, spot distance of 4.5 μm for the
lenticule and 2 μm for its border, and pulse energy of level 30 in the software, which
corresponds to approximately 150 nJ (Vestergaard et al. 2014b). The target refractive error
correction was directly inserted in the software without applying any nomogram. After laser
treatment, the patient was moved to the surgical microscope for the second part of the
procedure, which involves: (1) delineating front and back lenticule surfaces; (2) surface
separation using the standard lamellar corneal surgical technique of moving the instrument back
and forth using a blunt circular tip (Femto Double-Ended instrument [G-33954]; Carl Zeiss
Meditec AG) starting with the complete dissection of the front cap and following with the
dissection of the posterior lenticule surface; (3) lenticule extraction with forceps (Lenticule
Forceps [G-33961]; Carl Zeiss Meditec AG); and (4) pressing the corneal surface from center to
periphery using a dry micro-spear and drying the incision with the same. Finally, two drops of
combined tobramycin (0.3%) and dexamethasone (0.1%) were instilled in all cases at the end of
the procedure. Postoperative treatment included ofloxacin (0.3%) for 2 days, dexamethasone
drops five, three, two, and one time per day (reducing the dosage every 7 days), and sodium
hyaluronate (0.15%) for 1 month.
Outcome measures
Corneal biomechanical parameters widely described in the literature were obtained by the
Corvis ST (Bak-Nielsen et al. 2015; Chen et al. 2014). This system is based on the concept of
dynamic corneal topography, which combines the bidirectional applanation technology, the
high-speed photography, and the corneal topography (Piñero & Alcón 2015). An air puff is
directed over the
cornea and its response is captured by a Scheimpflug camera with a frame rate of 4,330 frames
per second along an 8-mm horizontal corneal coverage (Hon & Lam 2013). Multiple data are
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returned during the three stages into which the process can be divided: inward applanation
(AT1),
highest concavity, and outward applanation (AT2). The CCT output from the Corvis ST was
also used for the analysis because previous studies have reported nonsignificant differences or
no trends to overestimation or underestimation compared to the values obtained with the
Pentacam system (Oculus Optikgeräte GmbH, Wetzlar, Germany)(Bak-Nielsen et al. 2015) or
ultrasound pachymeters (Smedowski et al. 2014). A good intraobserver repeatability has been
reported for only some variables, including IOP, CCT, AT1, and AT2, and maximum
deformation amplitude (DA) at the corneal apex (Nemeth et al. 2013; Chen et al. 2014). On the
other hand, poorer intraclass correlation coefficients have been reported for peak distance, time
from starting until highest concavity, and first/ second applanation lengths or velocities (Nemeth
et al. 2013; Chen et al. 2014; Hon & Lam 2013). Therefore, only the most repeatable variables
(AT1, AT2, and DA) were included in this study, for which only one measurement per eye was
taken. Other variables such as air puff pressure at both applanation times were also considered
due to their potentially high clinical relevance for the analysis even though their repeatability
has not been previously reported. Because measurements were repeated for each eye 1 month
after SMILE, these postoperative measurements are identified by an apostrophe in the text (ie,
AT1’, AT2’, and DA’). Relative time changes due to the procedure were also computed for first
(diffAT1 = AT1 – AT1’) and second (diffAT2 = AT2 – AT2’) applanation times. A new
variable named corrected DA (DAc) was computed for DA by subtracting the CCT tissue
removed by the procedure from DA’ (DAc = DA’ – (CCT – CCT’)). DAc was computed
because it is known that the Corvis ST parameters depend on corneal thickness (Ariza-Gracia et
al. 2015). For the same deformation at the posterior corneal surface, the anterior surface is going
to experience a greater depth due to the removed CCT, as described in Figure 1.
Figure 1. Schematic showing the definition of corrected deformation amplitude (DA) depending on the removed corneal thickness. CCT = central corneal thickness; CCT’ = central corneal thickness at 1 month postoperatively; DA’ = deformation amplitude at 1 month postoperatively; IOP = intraocular pressure; SMILE = small incision lenticule extraction.
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Three indexes (t1, t2, d) were computed for comparison purposes between this study and future
Corvis ST studies with other refractive surgery techniques. These indexes were calculated by
means of the ratio of the difference for each variable before and after the procedure and the
change in CCT due to the procedure as follows:
Statistical analysis
Only the right eye of the patients was included in the statistical analysis, except if this eye
showed one of the alert messages included in the exclusion criteria. In such cases, the left eye
was included instead of the right eye. Normal data distributions were confirmed with the
Shapiro–Wilks W test for the comparison between groups and with the Kolmogorov–Smirnov
test for differences between preoperative and postoperative variables. Paired t tests were
conducted for testing differences before and after the procedure and Pearson r for evaluating
correlations. The sample was divided into three groups according to the myopia level: low from
-1.00 to -3.00 D, medium from -3.25 to -5.00 D, and high from -5.25 to -7.25 D. A one-way
analysis of variance with Bonferroni-adjusted post hoc comparisons was used to evaluate the
differences in variables among the three myopic groups. Data were analyzed using SPSS for
Windows statistical software (version 20.0; SPSS, Inc., Chicago, IL) and all of the statistical
tests were selected after checking that the required assumptions were completely accomplished.
Sample size calculation was performed to confirm whether the sample of eyes included in the
current study was of adequate size using the software PS version 3.1.2 (free availability online:
http://biostat.mc.vanderbilt.edu/wiki/Main/PowerSampleSize). This software uses the Dupont
and Plummer approach for sample size calculation (Dupont & Plummer 1990). We estimated
the number of pairs of patients needed to detect a true difference in population means d with
type I error probability a given a standard deviation s. Specifically, for a statistical power of
80%, considering d and s changes after SMILE reported for DA, AT1, and AT2 in previous
studies (Hassan et al. 2014; Frings et al. 2015; Chen et al. 2014; Pedersen et al. 2014; Shen et al.
2014), and an a error of 0.05, the sample size required was 61 eyes.
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64
2.2.4. Results
Eight eyes were excluded from the study for the following reasons: 3 eyes had an IOP greater
than 19 mm Hg before or after SMILE, 4 eyes had higher CCT after SMILE than before
surgery, and the Corvis ST pressure at AT2 was 164 mm Hg in 1 eye, which was considered as
an outlier. A total of 68 eyes of 68 patients distributed in 25 low, 32 medium, and 11 high
myopic eyes were included in the analysis (Table 1).
Table 1. Baseline demographic characteristics of all patients group
Mean ± SD (Range)
Low (n=25) Medium (n=32) High (n=11) Total (n=68)
Sex (female/male) 13/12 18/14 5/6 36/32
Age (yrs) 29.96 ± 5.81 (19 to 42)
31.97 ± 6.09 (22 to 46)
33.09 ± 6.81 (23 to 43)
31.41 ± 6.13 (19 to 46)
Intraocular Pressure (mmHg)
15.38 ± 2.28 (11.50 to 19.00)
14.63 ± 1.91 (10.00 to 18.50)
15.27 ± 2.82
(11.00 to 19.00)
15.01 ± 2.21 (10.00 to 19.00)
Spherical Equivalent Refraction (D)
-2.34 ± 0.55 (-1 to -3.13)
-4.12 ± 0.58 (-3.25 to -5.13)
-6.17 ± 0.62 (-5.75 to -7.25)
-3.80 ± 1.45 (-1 to -7.25)
Astigmatism (D) -0.78 ± 0.56 (0 to -1.75)
-0.53 ± 0.55 (0 to -2.00)
-1.09 ± 0.98
(0 to -3.00)
-0.71 ± 0.66 (0 to -3.00)
Simulated Keratometry at 3 mm (mm)
7.73 ± 0.25 (7.21 to 8.21)
7.76 ± 0.37 (7.06 to 8.86)
7.84 ± 0.27
(7.39 to 8.26)
7.76 ± 0.31 (7.06 to 8.86)
Central Corneal
Thickness (m)
553 ± 28 (494 to 604)
550 ± 22 (508 to 603)
545 ± 20
(518 to 577)
550 ± 24 (494 to 604)
Applanation times
Table 2 shows the changes in preoperative and postoperative variables. AT1 was advanced and
AT2 was delayed significantly after SMILE, whereas highest concavity did not vary. The
difference between the relative changes at first and second applanation times due to SMILE was
not significant, neither for times (|diffAT1| – |diffAT2|) nor for Corvis ST pressures (|diffPA1| –
|diffPA2|). We found a significant correlation between AT1 and CCT that increased after
SMILE (Table A, available in the online version of this article). However, no significant
correlations were found between AT2 and CCT before and after the surgery or for simulated
keratometry with AT1 and AT2 (Table A). The proposed biomechanical indexes were 5.26 ±
3.95 (range: -5.49 to 15.58) for t1 and -5.79 ± 6.32 (range: -22.04 to 13.02) for t2. These
indexes among refractive error groups are detailed in Table B.
Table A. Pearson correlations between outcome variables.
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AT1 and AT2: Times at first and second applanations; CCT: Central Corneal Thickness; DA: Deformation amplitude; DAc: Corrected postoperative deformation amplitude; SimK: Keratometry at 3 mm; Rx: Preoperative spectacle refraction
Table B. Outcome variables depending on the refractive error.
Mean ± SD (Range)
Low (n=25) Medium (n=32) High (n=11) F (One-way ANOVA)
P
diffAT1 0.30 ± 0.27 (-0.33 to 0.72)
0.34 ± 0.24 (-0.16 to 0.83)
0.59 ± 0.22 (0.21 to 0.81)
5.635 P = .007
Low versus Medium P>.05; Low versus High P = .005; Medium vs. High P = .019
diffAT2 -0.35 ± 0.38 (-1.08 to 0.66)
-0.36 ± 0.43 (-1.34 to 0.61)
-0.62 ± 0.28 (-1.08 to -0.21)
2.1 P = .13
t1 6.03 ± 5.36 (-5.49 to 15.58)
4.48 ± 2.95 (-3.34 to 9.04)
5.73 ± 2.28 (2.30 to 9.32)
1.181 P = .31
t2 -7.41 ± 7.79 (-22.04 to 10.75)
-4.45 ± 5.42 (-17.43 to 13.02)
-5.99 ± 2.89 (-12.47 to -2.09)
1.568 P = .22
DA (mm) 1.02 ± 0.09 (0.83 to 1.17)
1.07 ± 0.09 (0.93 to 1.26)
1.05 ± 0.1 (0.90 to 1.20)
2.431 P = .096
DA’ (mm) 1.09 ± 0.09 (0.86 to 1.28)
1.14 ± 0.1 (0.92 to 1.37)
1.18 ± 0.08 (1.06 to 1.29)
3.778 P = .02
Low versus Medium P>.05; Low versus High P = .03; Medium vs. High P>.05
DAc (mm) 1.04 ± 0.1 (0.80 to 1.23)
1.07 ± 0.1 (0.85 to 1.29)
1.07 ± 0.08 (0.96 to 1.27)
0.761 P = .47
d -1.61 ± 1.79 (-5.10 to 1.67)
-0.95 ± 1.14 (-3.53 to 1.62)
-1.18 ± 0.79 (-2.16 to 0.57)
1.605 P = .21
diffAT1 and diffAT2: Relative changes in times on first and second applanations due to SMILE; t1 and t2: Indexes obtained from the ratio between the change in time and change in thickness; DA: Preoperative deformation amplitude; DA’: Postoperative deformation amplitude; DAc: Postoperative deformation amplitude subtracting the removed corneal thickness; d: Index obtained from the ratio between the change in DA and change in thickness.
Table 2. Outcome variables before and after SMILE
Pre-SMILE Post-SMILE
AT1 (ms) vs CCT r=0.368, P=.002 r=0.42, P<.0001 AT2 (ms) vs CCT r=-0.149, P=.23 r=-0.116 P=.35
AT1 (ms) vs SimK (mm) r=-0.125, P=.31 r=-0.35, P=.003 AT2 (ms) vs SimK (mm) r=-0.027, P=.83 r=0.058, P=.64
DA (mm) vs Rx r=-0.159, P=.2 r=-0.349, P=.004 DAc (mm) vs Rx r=-0.141, P=.25
Pre – Post Variable (units) Mean ± SD (Range)
(Abbreviation) Pre-SMILE Post-SMILE Difference t (Paired t-test) P
AT1 – AT1’ (ms) (diffAT1)
7.79 ± 0.24 (7.26 to 8.25)
7.43 ± 0.23 (6.82 to 8.09)
0.37 ± 0.27 (-0.33 to 0.83)
11.4 < 0.0001
AT2 – AT2’ (ms) (diffAT2)
22.17 ± 0.44 (21.29 to 23.16)
22.57 ± 0.44 (21.57 to 23.36)
-0.4 ± 0.4 (-1.34 to 0.66)
-8.12 < 0.0001
HCT –HCT’ (ms) 17.20 ± 0.51 (15.71 to 18.02)
17.20 ± 0.56 (16.17 to 18.48)
0.000 ± 0.57 (-1.16 to 1.39)
.000 .1
PA1 – PA1’ (mmHg) (diffPA1)
52.9 ± 5.44 (40 to 63.40)
44.47 ± 5.40 (29.40 to 59.30)
8.43 ± 5.97 (-7.20 to 20.60)
11.64 < 0.0001
PA2 – PA2’ (mmHg) (diffPA2)
61.53 ± 10.81 (39.70 to 84.30)
52.02 ± 10.27 (31.80 to 80.30)
9.52 ± 10.79 (-18.90 to 31.90)
7.28 < 0.0001
CCT – CCT’ (m) 550 ± 24 (494 to 604)
478 ± 36 (415 to 550)
72 ± 25 (20 to 137)
24.14 < 0.0001
SimK – SimK’ (mm) 7.76 ± 0.31 (7.06 to 8.86)
8.35 ± 0.43 (7.32 to 9.44)
-0.58 ± 0.34 (-1.49 to 0.43)
-14.13 < 0.0001
DA – DA’ (mm) 1.05 ± 0.09 (0.83 to 1.26)
1.13 ± 0.1 (0.86 to 1.37)
-0.08 ± 0.08 (-0.27 to 0.1)
-8.1 < 0.0001
DA - DAc (mm) 1.05 ± 0.09 (0.83 to 1.26)
1.06 ± 0.09 (0.80 to 1.29)
-0.01 ± 0.08 (-0.20 to 0.18)
-1.13 .26
|diffAT1| – |diffAT2| -0.03 ± 0.23 (-0.65 to 0.52) -1.02 .31
|diffPA1| – |diffPA2| -1.09 ± 6.33 (-15.20 to 15.40) -1.42 .16
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66
AT1 and AT2: Times at first and second applanations; HCT: Time at highest concavity; PA1 and PA2: Air puff pressures at first and second applanations; CCT: Central Corneal Thickness; SimK: Simulated keratometry at 3 mm; DA: Deformation amplitude; DAc: Corrected deformation amplitude with the removed CCT; diffAT1 and diffAT2: Relative differences between preoperative and postoperative AT1 and AT2; diffPA1 and diffPA2= Relative difference between preoperative and postoperative PA1 and PA2. An apostrophe over each variable represents its postoperative value.
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DA
Table 2 shows how DA was increased significantly after SMILE. However, when the removed
CCT was subtracted from the DA’ (DAc), this difference between preoperative and
postoperative DA disappeared. The refractive error treated was correlated with DA’ but not with
DA and DAc (Table A). Comparison between myopic groups is shown in Table B and Figure 2.
The groups showed no differences in DA before SMILE (P = .096); significant differences were
presented in DA’, but only between the low and high myopic groups, as revealed in the post hoc
comparison (P = .03). Furthermore, there were no statistically significant differences in the DA
between myopic groups for the corrected postoperative SMILE value (DAc) (P = .47). The
proposed index d was -1.23 ± 1.39 (range: -5.10 to 1.67) and no significant differences were
found among myopic
groups (Table B).
Figure 2. Maximum deformation amplitude depending on the preoperative refractive error before small incision lenticule extraction (SMILE) (DA), after SMILE (DA’), and after SMILE subtracting the removed corneal thickness (DAc). Significant differences were only found between low and high myopia for DA’ (P = .03).
2.2.5. Discussion
The cornea is a viscoelastic tissue; thus, its behavior is different during the loading and
unloading pressures of an air puff (Roberts 2014). This is shown in our study in which AT2 was
lower than AT1, indicating that the cornea needs more pressure to achieve AT1 than that
required during the recovering stage at AT2; this difference of pressures between applanation
times is called corneal hysteresis (Piñero & Alcón 2015). Corneal hysteresis has been defined as
a descriptor of the corneal viscoelastic properties, arguing that if the cornea were purely elastic,
these two pressure values would be the same (Roberts 2014). On the other hand, AT1 only
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68
describes the elastic properties because a fast applied load, as in the case of the air puff, will
result in an almost pure elastic response during the loading (Ariza-Gracia et al. 2015). Our
results show that SMILE leads
to an anticipation of AT1 and a retardation of AT2, indicating major resistance during the
inward stage and greater force of the cornea during the outward recuperation before surgery. On
the other hand, highest concavity remained constant after SMILE, which suggests that highest
concavity mainly depends on the time at which the top pressure of the pulse is achieved.
The preservation of corneal biomechanics in SMILE measured by means of corneal hysteresis
remains controversial. Some authors have not found significant differences in corneal hysteresis
measured with the Ocular Response Analyzer between SMILE and femtosecond lenticule
extraction (Vestergaard et al. 2014a; Kamiya et al. 2015) or femtosecond laser-assisted LASIK
(Agca et al. 2014). However, other studies have reported differences between SMILE and
LASIK for myopia greater than -6.00 D (Wang et al. 2014) or have suggested that the corneal
viscoelastic properties are better preserved in SMILE in comparison to LASIK (Wu et al. 2014).
In our study, we found that SMILE leads to an anticipation of AT1 and a retardation of AT2,
but the relative changes of time at both stages were not significantly different. This change
might be due to the smaller mass of the postoperative corneas that causes the anticipation of
AT1 and the retardation of AT2 (Simonini et al. 2016).
It has also been pointed out that corneal hysteresis is a meaningless parameter and the drop in
pressure observed between the two applanation times cannot be linked to viscous properties of
the stroma and can be attributed to the inertia (Simonini et al. 2016). According to the latter, our
results would describe a change only in the elastic properties of the cornea, which affect AT1
and AT2 in a similar way. However, we found that change in AT1 (diffAT1) was different
among refractive error groups but this did not happen for the change in AT2 (diffAT2).
Therefore, change in corneal thickness has a great impact on AT1, as also shown in the
correlation analysis between AT1 and CCT before and after surgery, but not in AT2. The new
indexes (t1 and t2) proposed in this study for comparison of refractive surgery procedures
consider the change in applanation times depending on the removed CCT. Thus, the differences
between refractive error groups for AT1 disappeared for the t1 index, demonstrating that this
variable should be corrected according to the CCT removed. Our results about correlations
between times and CCT are not completely in agreement with those obtained in other studies, in
which AT2 and CCT have shown significant
correlations in healthy eyes (Lee et al. 2016; Lanza et al. 2014). However, the significance in
correlations for AT2 and CCT in these studies were P = .043 and .031, considerably higher than
for AT1 and CCT (P < .005), which also demonstrate higher dependency of AT1 with CCT.
Therefore, it is possible that the discrepancy with these studies is due to the sample size or the
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statistical analysis.
Corneal finite element model has demonstrated that corneas with different stiffness can show
the same DA depending on the IOP and CCT (Ariza-Gracia et al. 2015). In our study, we
assumed that IOP remains constant after the procedure because the same eyes were compared
before and after SMILE. Therefore, changes in DA after SMILE should be mainly due to
changes in CCT or corneal stiffness. We hypothesized that DA is increased after SMILE,
mainly due to a change of thickness, considering that for the same deformation at the posterior
corneal surface, the anterior surface is going to experience a greater depth due to the removed
CCT. Under this hypothesis, we computed a new variable DAc by means of subtracting the DA’
from the removed CCT. Thus,
although DA was significantly increased after SMILE, no significant differences were found
between the DA and DAc, which means either SMILE does not affect the corneal stiffness or
the Corvis ST cannot detect little changes in corneal stiffness by means of the air puff. The
index d did not show statistically significant differences among groups such as DAc.
Our research may have limitations. First, postoperative measures were taken only 1 month after
surgery and even though Mastropasqua et al. (Mastropasqua et al. 2014) reported no significant
differences between 30 and 90 days for variables such as AT1, AT2, or DA, we believe that
higher CCT after SMILE than before surgery might be explained by a slight increase of corneal
thickness by the postoperative dexamethasone treatment. Furthermore, the reason for other
outliers that were eliminated from the sample might be due not only to postoperative treatment
but also to a poor quality of the measurement considering that we only took one measurement
per eye. The indexes that we proposed for comparison with other techniques in future studies
should also be interpreted with caution. Although they consider the relative change in the Corvis
ST parameter according to the change in thickness that supposes an advantage for procedures
comparison, the standard deviation of these indexes is considerably high overall in the low
myopic group. It is possible that studies with longer follow-up and larger samples will reduce
the bias and the precision of these indexes will increase.
Studies that have compared the Corvis ST variables among different procedures have not
generally found differences between them (Pedersen et al. 2014; Shen et al. 2014). In our
opinion, studies comparing Corvis ST variables without information about the preoperative
values should be interpreted with caution because confounding variables such as IOP or CCT
can have a high impact on the results (Ariza-Gracia et al. 2015). Therefore, future studies
comparing techniques should include preoperative and postoperative data.
We have proposed three indexes (t1, t2, and d) for future comparisons between different
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70
refractive surgery techniques. These can only be applied in paired studies that include
preoperative and postoperative data assuming that the IOP of the patients remains constant after
the procedure. We decided to use these indexes, based on relative ratios, because they represent
the amount of change in a Corvis ST variable depending on the removed CCT. Thus, laser
refractive surgery procedures can be compared by the amount of change in a Corvis ST variable
that cannot be explained by a variation in corneal thickness. A technique with a higher index
would represent a cornea with a poorer preservation of the corneal biomechanical properties
because for the same removed thickness there would be a higher change in the Corvis ST
variable. To the best of our knowledge, no other studies have considered and evaluated the
relative change in Corvis ST variables according to the removed CCT. Therefore, our
approximation is the first to solve this problem and we believe that might improve the studies
for comparison between refractive surgery techniques until complex models for correcting
Corvis ST variables depending on CCT are developed.
We have demonstrated that if the Corvis ST parameters of time and DA represent the
biomechanical properties of the cornea, SMILE affects the corneal biomechanics because these
parameters change with surgery. However, we have also demonstrated that these changes are
mainly due to the removed corneal thickness. When this variable was corrected, differences
between myopia groups were not found and DA was equal to the preoperative values. Thus,
CCT correction might help to recognize variations in corneal biomechanics due to flap
generation or the stiffness characteristics of the tissue preserved instead of the volume of tissue
removed. For this purpose, we have proposed new indexes based on the relative change of
Corvis ST variables according to the removed CCT. These may help to improve studies of
comparison between refractive surgery techniques for answering the hypothesis of better
preservation of corneal biomechanics in SMILE that cannot be answered in this study. Similar
studies are required with other laser refractive surgery techniques. Future improvements in
Corvis ST parameters should be directed to correct the corneal thickness confounding variable
and comparison studies between
refractive surgery techniques should be based on differences between preoperative and
postoperative values to minimize the bias produced by other confounding variables such as the
IOP.
2.2.6. Disclosures
Dr. Fernández is a consultant for Carl Zeiss Meditec. The remaining authors have no financial
or proprietary interest in the materials presented herein.
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Smedowski, A. et al., 2014. Comparison of three intraocular pressure measurement methods including biomechanical properties of the cornea. Invest Ophthalmol Vis Sci, 55(2), pp.666–673.
Vestergaard, A.H. et al., 2014a. Central corneal sublayer pachymetry and biomechanical properties after refractive femtosecond lenticule extraction. J Refract Surg., 30(2), pp.102–8.
Vestergaard, A.H. et al., 2014b. Efficacy, safety, predictability, contrast sensitivity, and aberrations after femtosecond laser lenticule extraction. J Cataract Refract Surg, 40(3), pp.403–11.
Wang, D. et al., 2014. Differences in the corneal biomechanical changes after SMILE and LASIK. J Refract Surg, 30(10), pp.702–707.
Wu, D. et al., 2014. Corneal biomechanical effects: Small-Incision Lenticule Extraction versus Femtosecond Laser-Assisted laser in situ Keratomileusis. J Cataract Refract Surg, 40(6), pp.954–962.
Y Shen et al., 2014. Comparison of corneal deformation parameters after SMILE, LASEK, and femtosecond laser-assisted LASIK. J Refract Surg., 30(5), pp.310–8.
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2.3. New parameters for evaluating corneal biomechanics and intraocular
pressure after SMILE by Scheimpflug-Based Dynamic Tonometry.
Joaquín Fernández, MD;1 Manuel Rodríguez-Vallejo, PhD;*1 Javier Martínez, OD;1 Ana Tauste, MS; Patrizia Salvestrini, OD;1 David P Piñero, PhD;2,3
1Department of Ophthalmology (Qvision), Vithas Virgen del Mar Hospital, 04120, Almería, Spain 2Department of Optics, Pharmacology and Anatomy, University of Alicante, Alicante, Spain 3Department of Ophthalmology (OFTALMAR), Vithas Medimar International Hospital, Alicante, Spain *Corresponding author: manuelrodriguezid@qvision.es (Tel +34686500808)
2.3.1. Abstract
Purpose: To evaluate the new Corvis ST (CoST) parameters and dynamic corneal densitometry
(CD) in eyes operated on with small incision lenticule extraction (SMILE).
Setting: Qvision, Vithas Virgen del Mar Hospital, Almería, Spain
Design: Retrospective observational case series.
Methods: 43 subjects/eyes from a single institution undergoing SMILE surgery were included in
the study. Preoperative and one month postoperative measures of CoST were taken.
Scheimpflug images were analyzed to calculate dynamic CD. Changes in normal (IOP) and
biomechanically corrected (bIOP) intraocular pressure and stiffness parameter at first
applanation (SP-A1) were also evaluated (CoST 1.3r1469).
Results: Mean values for the difference in IOP and bIOP before and after surgery were 2.24 ±
1.26 mmHg (p = 0.001) and 0.57 ± 1.77 mmHg (p = 0.04), respectively. All CoST parameters
changed significantly after SMILE (p<0.05). The variation of each parameter was correlated
with the removed corneal thickness (p<0.05), except SP-A1 (p=0.15). None of the four dynamic
CD parameters defined changed significantly due to the surgery (p≥0.29). A new sign described
as a brightness inclined fringe moving through corneal periphery appeared preoperatively in
eyes with higher dynamic CD. This sign was more prevalent postoperatively (48.8% vs. 72.1%,
p = 0.04).
Conclusions: The bIOP measured after SMILE with the new CoST shows better agreement
with the preoperative values than IOP. SP-A1 is not dependent on the amount of removed
corneal thickness. An interesting new sign correlated with dynamic CD that might be related
with changes in corneal hydration and biomechanics has been reported.
Key Words: corneal biomechanics, SMILE, Corvis ST, intraocular pressure, refractive surgery
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2.3.2. Introduction
The corneal biomechanical properties have a significant influence on the prediction of laser
refractive surgery (LRS) outcomes (Roy & Dupps 2009) and might be related with the
development of corneal ectasia after surgery (Klein et al. 2006). For this reason, the interest in
the clinical measure of corneal biomechanics has increased in the past few years not only due to
these two major concerns, but also because of the emergence of new technologies for the in-
vivo characterization of corneal biomechanics, such as the Corvis ST (CoST) system (Oculus
Optikgeräte, Inc., Wetzlar, Germany) (Hon & Lam 2013), and new techniques of LRS, such as
the small incision lenticule extraction (SMILE) technique (Carl Zeiss Meditec, Jena, Germany).
This LRS technique has been suggested to theoretically preserve the corneal strength to a
greater degree than previous procedures (Reinstein et al. 2013).
The CoST system is a Scheimpflug-based dynamic corneal tonometer with a high-speed camera
which captures 4330 frames per second during the course of an air-puff of less than 30 ms and
along 8-mm of horizontal corneal coverage.3 Multiple outcome parameters have been derived
from each one of the three stages: inward applanation (A1), highest concavity (HC), and
outward applanation (A2) (Pedersen et al. 2014). Some of these parameters have been shown to
be associated to poor repeatability, such as peak distance, time from starting until HC, and
A1/A2 lengths or velocities (Hon & Lam 2013; Chen et al. 2014; Nemeth et al. 2013).
Likewise, the most repeatable parameters, A1/A2 times and deformation amplitude, have been
also questioned as they are conditioned by confounding variables such as central corneal
thickness (CCT) or intraocular pressure (IOP) (Fernández, Rodríguez-Vallejo, et al. 2016) that
must be considered in research studies in order to avoid possible misinterpretations
(Vinciguerra, Elsheikh, et al. 2016).
The conclusions obtained from clinical research studies using the CoST system and comparing
LRS techniques still remain controversial. Chen et al (Chen et al. 2014) reported differences
between photorefractive keratectomy (PRK) and virgin eyes, but Pedersen et al (Pedersen et al.
2014) did not find differences between control eyes and eyes undergoing laser in situ
keratomileusis (LASIK), femtosecond lenticule extraction (FLEX) or SMILE groups for all
variables except for the A1 deflection length. Shen et al. (Shen et al. 2014) demonstrated that
changes in CoST parameters were due to lenticule extraction and not to lenticule creation in
eyes undergoing SMILE. Osman et al. (Osman et al. 2016) reported greater reduction of
biomechanical properties in LASIK than in SMILE, contrary to Sefat et al (Sefat et al. 2016)
who found equal differences in a good study controlling confounding variables through
subgroups.
The new CoST software (1.3r1469) offers new parameters for improving the measure of the
IOP and corneal biomechanics by reducing the influence of confounding variables and including
normative values (Vinciguerra, Elsheikh, et al. 2016). The aim of this retrospective study was to
test these new parameters in eyes before and after SMILE and also to evaluate the dynamic
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corneal densitometry (CD) as a potential future clinical measure.
2.3.3. Methods
Patients
This study was approved by the Ethics Committee of Research from Almería Center
(Torrecardenas Hospital Complex) and performed in adherence to the tenets of the Declaration
of Helsinki. Data from fifty-four subjects operated on with the SMILE technique at Qvision
(Department of Ophthalmology, Virgen del Mar Hospital) were extracted from our historic
CoST database. Inclusion criteria included myopic patients with spherical equivalent from -1.00
D to -7.00 D and refractive astigmatism below 2.25 D. Manifest refraction was measured
preoperatively and one month after SMILE with CoST. Preoperative exclusion criteria were
pregnancy at time of surgery or follow-up, a preoperative central corneal thickness of less than
480 µm, an expected postoperative residual stromal bed of less than 250 µm, topographic map
compatible with subclinical keratoconus or other ectatic corneal disorder, and any other ocular
disease for which LRS procedures are not indicated (Shetty et al. 2015). Those patients with
alert messages in the CoST measurement of “Pressure Profile” and “Lost Images” indicating a
poor quality of the measure were excluded. However, measurements with other alerts were not
discarded in case the manual inspection resulted in a good delimitation of the corneal profile.
Surgical procedure
The same surgeon (JF) performed all the SMILE treatments with the VisuMax femtosecond
laser system (Carl Zeiss Meditec AG, Jena, Germany). Two drops of topical anesthesia
(Oxybuprocaine Hydrochloride 0.4%) were instilled at 5 minutes and 2 further drops at 1
minute before surgery. Optical principles and general description of the SMILE procedure have
been widely described (Reinstein et al. 2014), and the particular laser settings or surgical
maneuvers used in this study have been detailed in a previous work of our research group
(Fernández, Valero, et al. 2016). However, some additional important information about the
surgery include: the use of a cap diameter of 7.6 mm and cap thickness of 140 µm, the
performance of a peripheral incision of 2 mm with 30º of angle for posterior lenticule extraction
at 70º and the direct insertion of the target refractive error correction in the software without
applying any nomogram. After laser treatment, the patient was moved to the surgical
microscope for the second part of the procedure. Finally, 2 drops of tobramycin (3 mg) and
dexamethasone (1 mg) combination were instilled in all cases at the end of the procedure.
Postoperative treatment included ofloxacin (3 mg) during 2 days, dexamethasone drops 5, 3, 2
and 1 per day reducing the dosage each seven days and sodium hyaluronate (0.15%) during a
month.
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New CoST parameters
The CoST obtains the parameters among three stages during the air puff course: (1) the air puff
starts and the cornea is flattened in the center, this corresponds to A1 during the inward stage of
the air-puff; (2) the pressure continues up to the peak pressure, instant when the HC is achieved;
(3) the air puff pressure decreases and the cornea comes back to the baseline state achieving the
A2 just before to recover its original shape (Pedersen et al. 2014). New indexes have been
developed considering the corneal response at these three stages, including:
The biomechanically corrected intraocular pressure (bIOP): An estimate of the IOP for
minimizing the influence of different variables such as CCT and age over the
conventional IOP (Joda et al. 2016). The final bIOP included in the new CorvisST is a
modified algorithm of the previous published formula (Joda et al. 2016), which has
confirmed the previous results (Vinciguerra, Elsheikh, et al. 2016). The new version
takes the dynamic corneal response into consideration and it also corrects based on
radius at HC using a proprietary algorithm.
Deflection Amplitude Ratio (DAR): The ratio of the central corneal deflection and the
average of two points located at one (DAR1) or two (DAR2) millimeters at both sides
from the center. The deflection length is obtained by means of correcting the whole eye
movement and overlapping the peripheral cornea at the baseline state with the cornea at
the highest concavity (Cynthia Roberts 2016). Stiffer corneas would have lower DARs
as the corneal center and the cornea at 1 or 2 mm deflect at same time, whereas higher
DARs indicate that central cornea deflects more than the average of the other two other
points, corresponding to softer tissue.
Stiffness Parameter at First Applanation (SP-A1): Defined as the resultant pressure at
A1 from the difference between the air puff pressure at the corneal surface and the
bIOP, divided by the deflection amplitude (Cynthia Roberts 2016). Higher values
indicate stiffer corneas.
Integrated Inverse Concave Radius (IR): The integrated area under the curve of the
inverse concave radius, which is the radius of curvature during the concave phase of
deformation. Higher IR indicates softer tissue.
Corneal Biomechanical Index (CBI): Normalized index from 0 (normal) to 1
(abnormal) obtained by means of logistic regression with the combination of different
CoST parameters that enhances the sensitivity between keratoconic and healthy eyes
using a proprietary algorithm. These parameters include: DAR1, DAR2, velocity at A1,
standard deviation of deformation amplitude at HC, the Ambrosio relational thickness
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to the horizontal profile, and the SP-A1 (Vinciguerra, Ambrósio, et al. 2016).
Dynamic Corneal Densitometry
CD is a measure of the corneal backscattered light by the analysis of the Scheimpflug image
brightness represented in percentage of grey levels (Ní Dhubhghaill et al. 2014). Therefore, the
dynamic CD can be defined as the increase in the densitometry during the corneal deformation
by the air-puff. Four variables are distinguished: the maximum densitometry increase (DIM)
which is the maximum increase of densitometry achieved during the deformation, and the
densitometry increase (DI) at each one of the stages A1 (DI-A1), HC (DI-HC) and A2 (DI-A2).
CD variables are only included in the research software and not in the commercial version.
Statistical Analysis
Only right eyes were included in the sample, but the left eye was included instead of the
right if exclusion messages appeared in the measurement of such eye. Outliers from the
difference between preoperative and postoperative measures were identified by plotting
and analyzing the boxplots. Those cases at more than 1.5 box-lengths of the edge of the
box were considered as outliers. Eleven out of 54 cases were identified as outliers and
an individual data inspection was performed in order to verify the reliability of the data.
These cases were finally excluded after verifying that were erroneous and not reliable
measurements: higher corneal thickness after surgery than before (4 cases), higher
intraocular pressure after surgery (3 cases), and alert messages of model deviation (4
cases). Paired t-tests were conducted for testing differences before and after the
procedure and Pearson r for evaluating correlations. For all the variables which were not
normally distributed, the Wilcoxon signed rank test was used for testing paired
differences and spearman rho for correlations. Bland-Altman plots were used to
evaluate the agreement between preoperative and postoperative IOPs. Measures were
classified in two time slots, from 9:00 to 15:00 and from 15:00 to 21:00, in order to
compute mean differences for measures taken during the same time slot.
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2.3.4. Results
A total of 43 eyes from 18 men and 23 women of mean age 31.63 ± 6.55 years old
(range, 22 to 45 years) were included in the analysis. The mean preoperative spherical
equivalent was -3.87 ± 1.43 D (range, -1.00 to -6.88 D).
New CoST parameters
The IOP and bIOP parameters correlated significantly with the subjects’ age before
SMILE (Table 1). Significant mean differences were obtained, either for IOP or bIOP,
between preoperative and postoperative values, although differences were lower for
bIOP (Table 2). The removed CCT was significantly correlated with the change in IOP,
but not with the variation in bIOP (Table 3). The mean difference in hours throughout
the day between the preoperative measure and the postoperative measure was
significantly correlated with the mean bias due to surgery, either for IOP and bIOP (r = -
0.42, p = 0.006). A total of 15 subjects were measured at the first time slot
preoperatively and in the second post-operatively. A total of 21 subjects were measured
at the same time slot resulting in a mean bias of 2.24 ± 1.26 mmHg for IOP (z=-3.32, p
= 0.001) and 0.57 ± 1.77 mmHg for bIOP (z=-2.09, p = 0.04).
Table 1. Spearman rho correlations between age and the preoperative and postoperative parameters. Age
Preoperative Postoperative Difference ()
IOP (mmHg) 0.39, p=0.02* 0.08, p=0.62 0.33, p=0.03* bIOP (mmHg) 0.32, p=0.04* -0.01, p=0.93 0.25, p=0.10 SP-A1 (mmHg/mm) 0.23, p=0.13 0.27, p=0.08 -0.14, p=0.37 DAR1 -0.42, p=0.005* -0.28, p=0.07 -0.04, P=0.81 DAR2 -0.39, p=0.01* -0.29, p=0.06 -0.001, p=0.99 IR (mm-1) -0.22, p=0.15 -0.18, p=0.25 0.006, p=0.97 CBI -0.34, p=0.03* -0.26, p=0.09 0.24, p=0.12 DIM (%) -0.52, p<0.001* -0.15, p=0.33 -0.14, P=0.36 DI-A1 (%) -0.42, p=0.005* -0.29, p=0.06 -0.14, P=0.36 DI-HC (%) -0.50, p<0.001* -0.13, p=0.41 -0.17, P=0.29 DI-A2 (%) -0.24 p=0.12 -0.01, p=0.95 -0.16, p=0.31
IOP= Non-contact intraocular pressure; bIOP = Biomechanical corrected IOP; SP-A1 = Stiffness parameter; DAR = Deflection amplitude ratio at 1 mm (DAR1) and 2 mm (DAR2); IR = Integrated inverse curvature radius; CBI = Corneal biomechanical index; DIM = Densitometry increase maximum; DI = Densitometry increase at A1 (DI-A1), HC (DI-HC) and A2 (DI-A2). * p <0.05
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Table 2. Differences between preoperative and postoperative measures, excluding the outliers.
Variable Pre-SMILE mean ± SD [range] median, IR [range]
Post-SMILE mean ± SD [range] median, IR [range]
t-test
wilcoxona
IOP (mmHg) 15 ± 2.53 [11 to 23]
11.80 ± 1.92 [8 to 17.50]
t= 7.69, p<0.001*
bIOP (mmHg) 14.68 ± 1.99 [11 to 21.60]
13.30 ± 1.74 [10.80 to 17.70]
t= 3.99, p<0.001*
SP-A1 (mmHg/mm) 148.95 ± 12.94 [126.61 to 183.87]
142.48 ± 17.31 [101.67 to 176.79]
t= 3.05, p=0.004*
DAR1 1.56 ± 0.55 [1.43 to 1.71]
1.67 ± 0.06 [1.52 to 1.79]
t= -13.96, p<0.001*
DAR2 4.18 ± 0.40 [3.23 to 4.92]
5.16 ± 0.56 [3.65 to 6.26]
t= -18.07, p<0.001*
IR (ms*mm-1) 6.87 ± 0.98 [4.91 to 9.07]
9.17 ± 1.25 [6.54 to 12.62]
t= -22.75, p<0.001*
CBI 0.002, 0.16 [0 to 0.09]
0.42, 0.86 [0 to 1]
z= 5.58, p<0.001a*
DIM (%) 31.05 ± 4.47 [22.93 to 44.26]
29.68 ± 5.92 [15.23 to 40.81]
t= 1.49, p=0.14
DI-A1 (%) 6.25 ± 1.85 [3.04 to 11.74]
6.26 ± 1.44 [3.97 to 9.75]
t= -0.06, p=0.95
DI-HC (%) 30.55 ± 4.43
[22.70 to 43.78] 28.99 ± 6.02
[14.04 to 40.63] t= 1.67, p=0.10
DI-A2 (%) 10.99, 2.94 [6.66 to 17.67]
11.72, 4.18 [-2.91 to 42.86]
z= 1.04, p=0.30a
t-test for paired samples. Mean ± Standard Deviation (SD) is shown. a wilcoxon signed-rank test. Median, Interquartile Range (IR) is shown. IOP= Non-contact intraocular pressure; bIOP = Biomechanical corrected IOP; SP-A1 = Stiffness parameter; DAR = Deflection amplitude ratio at 1 mm (DAR1) and 2 mm (DAR2); IR = Integrated inverse curvature radius; CBI = Corneal biomechanical index; DIM = Densitometry increase maximum; DI = Densitometry increase at A1 (DI-A1), HC (DI-HC) and A2 (DI-A2). * p <0.05
Table 3. Correlations between the variation of variables from preoperative to postoperative and the
removed corneal thickness.
CCT DIM DI-A1 DI-HC DI-A2
IOP (mmHg) r= 0.42*, p=0.005
r= -0.58*, p<0.001
r= -0.001, p=0.99
r= -0.55*, p<0.001
ρ = -0.31*, p=0.04
bIOP (mmHg) r= 0.24, p=0.12
r= -0.58*, p<0.001
r= -0.03, p=0.85
r= -0.55*, p<0.001
ρ = -0.31*, p=0.04
SP-A1 (mmHg/mm) r= 0.23, p=0.15
r= -0.09, p=0.56
r= -0.04, p=0.79
r= -0.05, p=0.76
ρ = 0.02, p=0.92
DAR1 r= -0.48*, p=0.001
r= 0.09, p=0.58
r= -0.34*, p=0.03
r= 0.09, p=0.58
ρ = -0.05, p=0.73
DAR2 r= -0.50*, p=0.001
r= 0.17, p=0.28
r= 0.06, p=0.71
r= -0.13, p=0.39
ρ = -0.04, p=0.82
IR (ms*mm-1) r= -0.70*, p<0.001
r= 0.38*, p=0.01
r= 0.09, p=0.54
r= 0.35*, p=0.02
ρ = 0.12, p=0.44
CBI ρ = -0.47*, p=0.002
ρ = -0.12, p=0.45
ρ = 0.04, p=0.83
ρ = -0.08, p=0.59
ρ = -0.29, p=0.06
Pearson correlations (r) and spearman rho (ρ).
= Difference preoperative value – postoperative value; ρ = Spearman rho; r = Pearson r; IOP= Non-contact intraocular pressure; bIOP = Biomechanical corrected IOP; SP-A1 = Stiffness parameter; DAR = Deflection amplitude ratio at 1 mm (DAR1) and 2 mm (DAR2); IR = Integrated inverse curvature radius; CBI = Corneal biomechanical index; DIM = Densitometry increase maximum; DI = Densitometry increase at A1 (DI-A1), HC (DI-HC) and A2 (DI-A2). * p <0.05
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All new CoST parameters changed significantly after SMILE (Table 2). The increase in
DAR1 and DAR2 was 0.11 and 0.98, respectively, after surgery. Negative significant
correlations of both changes with the removed CCT (CCT) were found (Table 3). This
means that the more CCT was removed, the higher was the increment in DARs
(DARs). Similar behavior was obtained for IR, with a stronger correlation with CCT
than DARs (Table 3). The stiffness parameter SP-A1 decreased significantly after
SMILE and was not correlated with CCT (Table 3). None of variations of these
parameters described in Table 3 were significantly correlated with the age of the
subjects (p > 0.05)(See Difference in Table 1).
Dynamic Corneal Densitometry
Negative significant correlations were found between preoperative CD variables and
age but these significances disappeared after surgery (Table 1). No significant changes
in any of the densitometry parameters defined and evaluated were found after surgery
(Table 2). Correlations were also manifested for the variation of some of the previous
new CoST parameters and the modification of CD due to surgery (Table 3). The mean
percentage of DIM before SMILE was close to the mean achieved for DI-HC (Table 1).
Mean differences between DI-A1 and DI-A2 for the preoperative dataset were -5.11 ±
1.84 (paired t-test, t=-18.24, p<0.001). These tendencies were similar after SMILE, with
DIM also close to DI-HC and DI-A1 lower than DI-A2. An interesting sign was
observed at the dynamic response of the cornea described as a brightness inclined fringe
that appears in the corneal peaks at HC, moving to the corneal periphery during the
outward stage (Figure 1). The visualization of the 43 preoperative and postoperative
videos resulted in the recognition of this sign in 48.8% (n=21) of the preoperative
records and in 72.1% (n=31) of the postoperative records for the same eyes. This higher
prevalence of this sign postoperatively was statistically significant (McNemar's test, p =
.04).
A comparison of mean densitometry for eyes which presented the sign and those for
which the sign was not visible was performed either for preoperative and postoperative
records (Table 4). Eyes which showed the sign in the preoperative records had a higher
densitometry percentage for all the densitometry variables, but this difference was only
statistically significant for DI-A1.
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Table 4. Corneal densitometry in groups for which of the bright fringe in movement was shown (Sign) for
the preoperative and postoperative records.
Figure 1. Sign observed at the dynamic response of the cornea after SMILE surgery which is a brightness
inclined fringe that appears in the peripheral corneal peaks at the highest concavity stage (HC) (bottom
image), moving to the corneal periphery until its disappearance during the outward stage. This sign is not
commonly observed preoperatively (top image).
2.3.5. Discussion
In this study, we present the changes of new CoST parameters due to SMILE surgery
and we analyze the dynamic CD increase as a new potential variable for explaining
corneal biomechanics. We found better agreement between preoperative and
postoperative intraocular pressure for bIOP than for conventional IOP measured with
Preoperative Records; mean ± SD [range] or median, IR [range] Postoperative Records; mean ± SD [range] or median,
IR [range]
No Sign (n = 21)
Sign (n = 22)
t-test U Mann-Whitneyb
No Sign (n = 12)
Sign (n = 31)
t-test U Mann-Whitneyb
DIM (%) 29.45 ± 3.05
[22.93 to 35.12] 32.58 ± 5.11
[24.39 to 44.26] t=-2.43, p = 0.02*
28.40 ± 7.02 [15.23 to 39.95]
30.18 ± 5.48 [19.02 to 40.81]
t=-0.88, p = 0.38
DI-A1 (%) 5.49 ± 1.14
[3.04 to 7.46] 6.97 ± 2.12
[3.81 to 11.74] t=-2.86, p = 0.007*
5.44 ± 0.95 [3.97 to 6.97]
6.58 ± 1.48 [4.42 to 9.75]
t=-2.48, p = 0.02*
DI-HC (%) 28.91 ± 3.10
[22.70 to 34.28] 32.12 ± 4.99
[24.05 to 43.78] t=-2.52, p = 0.02*
27.88 ± 7.23 [14.04 to 39.95]
29.42 ± 5.55 [18.96 to 40.63]
t=-0.74, p = 0.46
DI-A2 (%) 10.67, 2.51
[6.66 to 14.28 ] 12.08, 3.08
[8.77 to 17.67] z=2.70, p = 0.007b*
11.85 ± 5.83 [1 to 22.86 ]
11.90 ± 2.89 [6.74 to 18.05 ]
z=-0.80 p = 0.42b
t-test for independent samples. Mean ± Standard Deviation (SD) is shown. b U Mann-Whitney. Median, Interquartile Range (IR) is shown. DIM = Densitometry increase maximum; DI = Densitometry increase at A1 (DI-A1), HC (DI-HC) and A2 (DI-A2). * p <0.05
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CoST. Despite of the fact that significant differences were found between preoperative
and postoperative means, these results should be interpreted with caution since some
measures were taken at different time slots. Considering that IOP decreases during the
day (David et al. 1992) and up to 15 patients were measured in the first time slot
preoperatively and in the second postoperatively, some differences can be explained by
this study limitation. In fact, we found a correlation between the difference in hours
along a day and mean IOP differences due to surgery in such a way that higher
differences in IOP were found for those patients measured early in the morning
preoperatively and in the evening postoperatively. After considering only the 21
subjects measured in the same time slot, the bias was reduced from 1.39 ± 2.28 mmHg
to 0.57 ± 1.77 mmHg for bIOP. The preoperative bIOP was slightly correlated with age,
even though this new parameter considers age in the correction algorithm (Vinciguerra,
Elsheikh, et al. 2016). On the other hand, the change of bIOP due to surgery was not
correlated with the amount of removed corneal thickness which suggests an important
improvement in the measure of intraocular pressure with the instrument.
The variation of some parameters, such as applanation times or deformation amplitude,
due to SMILE can be explained mainly by the removed corneal thickness (Fernández,
Rodríguez-Vallejo, et al. 2016). It is well known that CCT and IOP are confounding
variables that may influence on other CoST parameters (Y Shen et al. 2014). Therefore,
comparison studies of LRS techniques should be well designed with uniform samples
with same removal of CCT and preoperative IOP in order to avoid misinterpretations of
the results (Vinciguerra, Elsheikh, et al. 2016).
We found significant changes in all the new CoST parameters due to SMILE, but
interestingly all the parameters were significantly correlated with the removed CCT
except the stiffness parameter SP-A1. This suggests that this new parameter would be a
promising indicator to predict the biomechanical properties of the cornea with
independence of the tissue volume. We also found significant negative correlations
between DARs and CBI parameters with age indicating a slight decrease in both with
age; this is in agreement with the increase of stiffness with age (Elsheikh et al. 2007).
Conversely, the stiffness parameter SP-A1 was not correlated with age. All these
correlations became poorer after surgery which indicates that the normal age-related
corneal response might be altered due to surgery. However, this should be interpreted
with caution because the non-uniform correction of refractive errors for the different
ages.
Concerning densitometry, it is important to differentiate between static CD measured
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with Pentacam and dynamic CD measured with CoST. The first one represents the
natural state of the corneal fibrils and corneal hydration whereas the latter
hypothetically would represent the modification of collagen fibers order and fluidics
movement along the cornea during the air-puff course. In our series, at the baseline
state, the densitometry measured with Pentacam was maximal in the anterior 120 µm of
the cornea in comparison with the center and posterior layers (Ní Dhubhghaill et al.
2014). Considering that the normal epithelial thickness is around 53.4±4.6 μm (Elsheikh
et al. 2007) and that the lamellar angles relative to the stromal surface are highest in the
anterior-most 83 µm of the corneal stroma, our hypothesis is that the increase of the
anterior densitometry is not only due to epithelial thickness but also to the angle of the
collagen lamellae (Abass et al. 2015) at this part of the cornea and possibly due to the
fact that the anterior stroma tends to be less hydrated.
In the study of dynamic CD, we found that CD was increased during the inward stage
achieving the maximum close to the HC, whereas during outward stage the CD at A2
was higher than the obtained at A1. Ariza et at. (Ariza-Gracia et al. 2015) pointed out
that during the loading pressure the anterior stroma goes from a tension state to a
compression whereas the posterior stroma experiences greater tensional stress. Our
explanation about the course of dynamic CD is that the stromal fluid goes from the
anterior to the posterior stroma with the air puff pressure, whilst the anterior fibers are
compressed or reordered. Therefore, both corneal hydration (Wang et al. 2004) and
fibers arrangement (Leonard & Meek 1997) would play an important role in light
scattering. This should be confirmed in future studies.
Finally, we found in dynamic CD a clinical sign consisting of an inclined brightness
fringe which is moved through the corneal periphery. The origin of this sign has not
been previously reported and it is completely unknown. Our hypothesis is that this sign
might be explained by the reorder/compression of the fibers and the stromal fluid
repositioning through peripheral areas of less pressure in the stroma. Thus, the sign
would appear in corneas with higher hydration and greater dynamic CD. For a better
understanding, we attach a video that shows the dynamic CD profile preoperatively, at 1
month and 24 months after surgery in one eye from our series undergoing SMILE. As
displayed, the sign was not present preoperatively, appeared at 1 month and at 24
months after surgery is almost eliminated. Considering that the increase of corneal
backscattered light in Pentacam has been also correlated with the serum concentration
of the active metabolite N-desethylamiodarone during the amiodarone therapy
(Alnawaiseh et al. 2016), future research studies in treated versus untreated corneas
achieving different degrees of hydration would help to confirm our hypothesis. We also
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found that the dynamic CD decreases with the increase of the age whereas the static CD
measured with Pentacam have been reported to have the contrary effect (Ní Dhubhghaill
et al. 2014). This might be due to the formation of cross-links, decrease in interfibrillar
spacing and increase of collagen fibrils diameter (Quantock et al. 2015) which difficult
fibers reorder and fluidics transition with age (Whitford et al. 2015).
We are aware that our research has two potential limitations. First, postoperative
measures were taken only 1 month after surgery and some corneas might not be
stabilized by the recent end of post-operative ophthalmologic treatment. This may be
one reason explaining the presence of some atypical results (outliers) that were detected
and removed from the statistical sample. In any case, a reanalysis including the outliers
was also performed, but the results did not change the conclusions obtained in the study
(Table 5). Nevertheless, future studies should be conducted for longer periods of
follow-up because as it is shown in the attached video, the detected sign might appear
for reasons that are not covered in this work and this should be specifically investigated
in connection with corneal biomechanics. Second, an early study was not available in
order to compute the required sample for each one of the hypothesis managed in this
study. However, we conducted a posterior power analysis using G Power version 3.1
(available at http://www.gpower.hhu.de/) to confirm whether the sample of eyes
included was of adequate size to detect a true difference in population means () with
type I error probability () given a standard deviation (). Specifically, the sample was
enough for achieving a statistical power of 80%, considering and changes after
SMILE for all the new parameters. However, for detecting differences in CD among the
groups that presented or not the sign, the statistical power decreased to 76% for DIM,
and 70% for DI-HC in the preoperative records suggesting the need of a higher sample
in future studies involving CD.
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Table 5. Differences between preoperative and postoperative measures, including the outliers. Variable Pre-SMILE
mean ± SD [range] median, IR [range]
Post-SMILE mean ± SD [range] median, IR [range]
t-test
wilcoxona
IOP (mmHg) 14.50, 3.50 [10 to 26]
11.50, 3.00 [8 to 17.50]
z= -5.51, p<0.001a*
bIOP (mmHg) 14.74 ± 2.39 [10.10 to 23.90]
13.38 ± 1.85 [10.60 to 17.70]
t= 4.11, p<0.001*
SP-A1 (mmHg/mm) 148.48 ± 13.89 [123.31 to 183.87]
142.30 ± 17.03 [101.67 to 176.79]
t= 3.22, p=0.002*
DAR1 1.56, 0.06 [1.43 to 2.01]
1.66, 0.1 [1.50 to 1.79]
z= 5.45 p<0.001 a*
DAR2 4.22, 0.58 [3.23 to 8.04]
5.13, 0.82 [3.65 to 6.26]
z= 5.77, p<0.001a*
IR (ms*mm-1) 6.86, 1.24 [4.91 to 10.03]
9.10, 1.81 [6.54 to 12.62]
z= 6.15, p<0.001a*
CBI 0.002, 0.01 [0 to 1]
0.27, 0.85 [0 to 1]
z= 5.67, p<0.001a*
DIM (%) 30.60, 5.17 [7.74 to 44.26]
29.05, 9.11 [1.11 to 40.81]
z= -1.38, p=0.17a
DI-A1 (%) 5.91, 2.41 [1.14 to 37.92]
6.16, 2.29 [-11.38 to 41.48]
z= 0.82, p=0.41a
DI-HC (%) 29.90, 5.47
[-36.32 to 43.78] 27.77, 9.26
[-52.48 to 40.63] z= -1.51, p=0.13a
DI-A2 (%) 11.06, 3.69 [-30.13 to 54.00]
12.03, 4.43 [-44.60 to 57.00]
z= 1.88, p=0.06a
t-test for paired samples. Mean ± Standard Deviation (SD) is shown. a wilcoxon signed-rank test. Median, Interquartile Range (IR) is shown. IOP= Non-contact intraocular pressure; bIOP = Biomechanical corrected IOP; SP-A1 = Stiffness parameter; DAR = Deflection amplitude ratio at 1 mm (DAR1) and 2 mm (DAR2); IR = Integrated inverse curvature radius; CBI = Corneal biomechanical index; DIM = Densitometry increase maximum; DI = Densitometry increase at A1 (DI-A1), HC (DI-HC) and A2 (DI-A2). * p <0.05
In conclusion, biomechanical changes characterized using the new parameters provided
by the CoST system occur after SMILE. SP-A1 has not shown correlations with the
removed CCT which supposes an advance for avoiding the effect of confounding
variables, and preoperative DARs and CBI are able to predict the increase of corneal
stiffness with age. Likewise, the postoperative bIOP measured with the improved
version of the CoST shows better agreement with the preoperative values than IOP with
independence of CCT. For bIOPs measured during the same time slot, the preoperative
bIOP can be estimated adding 0.57 mmHg in subjects operated on SMILE. Considering
the standard deviation of 1.77 mmHg, the maximum bias after applying this correction
would be of 2x1.77 = 3.54 mmHg with a 95% of confidence. The dynamic CD have not
shown significant differences due to surgery and an interesting new sign that might be
related with changes in corneal hydration and biomechanics has been reported even
though some caution should be taken before to assume this relationship because it is a
hypothesis that must be tested in controlled studies in vitro or in vivo. Future research
including this new parameter would help to understand the structure of the cornea in
terms of collagen fibers order and hydration after SMILE.
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2.3.6. Disclosures
a. Funding/Support: Authors have not received financial support to conduct this
research.
b. Financial Disclosures: J.F. reports personal fees from OCULUS and personal fees
from ZEISS, outside the submitted work. The remaining authors have nothing to
disclose.
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2.3.7. References
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Chen, X. et al., 2014. Reliability of corneal dynamic Scheimpflug analyser measurements in virgin and post-PRK eyes. PLoS ONE, 9(10), p.e109577.
Cynthia Roberts, 2016. Two novel stiffness parameters for the Corvis® ST. In XXXIV Congress of the ESCRS. Copenhagen. Available at: http://www.corneal-biomechanics.de/.
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Fernández, J., Rodríguez-Vallejo, M., et al., 2016. Corneal thickness after SMILE affects scheimpflug-based dynamic tonometry. Journal of Refractive Surgery, 32(12), pp.821–828.
Fernández, J., Valero, A., et al., 2016. Short-term outcomes of small-incision lenticule extraction (SMILE) for low, medium, and high myopia. European Journal of Ophthalmology, Jul 18(0), pp.0–0.
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Klein, S.R. et al., 2006. Corneal ectasia after laser in situ keratomileusis in patients without apparent preoperative risk factors. Cornea, 25(4), pp.388–403.
Leonard, D.W. & Meek, K.M., 1997. Refractive indices of the collagen fibrils and extrafibrillar material of the corneal stroma. Biophysical Journal, 72(3), pp.1382–1387.
Nemeth, G. et al., 2013. Repeatability of ocular biomechanical data measurements with a Scheimpflug-based noncontact device on normal corneas. J Refract Surg., 29, pp.558–63.
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Pedersen, I.B. et al., 2014. Corneal biomechanical properties after LASIK, ReLEx flex, and ReLEx smile by Scheimpflug-based dynamic tonometry. Graefes Arch Clin Exp Ophthalmol., 252(8), pp.1329–35.
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outcomes. Eye and Vision, 1(1), p.3. Reinstein, D.Z., Archer, T.J. & Randleman, J.B., 2013. Mathematical model to compare
the relative tensile strength of the cornea after PRK, LASIK, and small incision lenticule extraction. J Refract Surg., 29(7), pp.454–60.
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Sefat, S.M.M. et al., 2016. Evaluation of changes in human corneas after femtosecond laser-assisted LASIK and Small-Incision Lenticule Extraction (SMILE) using non-contact tonometry and ultra-high-speed camera (Corvis ST). Current Eye Research, 41(7), pp.917–922.
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Vinciguerra, R., Elsheikh, A., et al., 2016. Influence of pachymetry and intraocular pressure on dynamic corneal response parameters in healthy patients. Journal of Refractive Surgery, 32(8), pp.550–561.
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CAPÍTULO 3 DISCUSIÓN DE LOS RESULTADOS
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3.1 Discusión de los resultados.
La inclusión de cualquier nuevo procedimiento de cirugía refractiva comienza
con la evaluación de los resultados de eficacia, seguridad y predictibilidad. Estos
adquieren especial importancia durante los primeros sujetos sometidos a la nueva
cirugía, en los cuales entra en juego la curva de aprendizaje del cirujano. El primero de
los artículos incluidos en esta Tesis por compendio de artículos se centra en la
evaluación de los resultados de seguridad, eficacia y predictibilidad para los 71
primeros sujetos intervenidos con SMILE por un cirujano experimentado en cirugía
refractiva, pero sin experiencia previa en la técnica. Para las condiciones metodológicas
particulares de este estudio, encontramos que la agudeza visual con corrección tras el
procedimiento se mantenía estable en un 95.8% de los casos, con tan solo un 1.4% (1
ojo) perdiendo una línea de agudeza visual con la mejor corrección. A estos resultados
de seguridad se suma la presencia tan solo de una pérdida de succión con las
complicaciones secundarias de endocrecimiento epitelial, pliegues corneales y
astigmatismo irregular.
Una de las ventajas de nuestra metodología frente a estudios similares es la
estratificación de la muestra en tres niveles de error refractivo, bajo, medio y alto. Esta
estratificación permite evaluar en mejor medida la predictibilidad de la técnica.
Considerando todo el rango de error refractivo, nos encontramos una pendiente para la
curva que relaciona error refractivo planificado y tratado realmente de 0.95 (R2 = 0.99).
Esto describe una hipocorrección de la miopía con el incremento del error de refracción.
La comparativa del error de refracción posoperatorio en los tres grupos resultó en
diferencias significativas con medianas sobre la emetropía (0 D) para errores de
refracción entre -1.00 D y -5.00 D, mientras que la mediana para el grupo de alta miopía
(entre -5.25 D y -7.00 D) se encontraba en -0.50 D, sugiriendo la necesidad de una
corrección del nomograma de tratamiento en aquellos casos en los que la miopía supere
las -5.00 D.
La tendencia a la hipocorrección del grupo de alta miopía se encuentra
relacionada con los resultados de eficacia. Mientras que el 67% y 74% de los grupos de
baja y media miopía alcanzaban una agudeza visual sin corrección de 20/20, tan solo el
50% alcanzó dicho valor en el grupo de alta miopía. Pese a los peores resultados en el
grupo de alta miopía, la mediana se encontró sobre 20/20 en los tres grupos sin
diferencias significativas entre ellos. La comparación entre los resultados de agudeza
visual preoperatoria con gafas y postoperatoria sin gafa mostró un menor porcentaje de
sujetos (17% frente a 4%) alcanzando valores por encima (20/16) de la agudeza
considerada como normal (20/20). Esta disminución fue notablemente más marcada en
el grupo de baja miopía, en el que 23% de los sujetos que tenían 20/16 antes de la
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operación con su mejor corrección pasaron a ser 7% sin gafa tras la operación y del 97%
con 20/20 pasaron a 67%. La explicación de este mayor salto en el caso de la baja
miopía se debe principalmente al efecto de magnificación de la gafa que reduce el
tamaño de las imágenes en mayor medida para los grupos de media y alta miopía y, por
tanto, reduce la agudeza visual preoperatoria con gafa. De hecho, tan solo el 81% y 61%
de los sujetos con miopías media y alta alcanzaban una agudeza visual de 20/20 antes de
la operación con su mejor corrección.
Los astigmatismos tratados en la muestra de estudio se encontraban en su gran
mayoría por debajo de 1 D bien sea a favor o en contra de la regla, tal y como muestran
las desviaciones estándar de 0.9 D en la horizontal y 0.7 D en la vertical de la figura de
doble ángulo. Éstas desviaciones se redujeron a 0.24 D y 0.27 D respectivamente,
mostrando los resultados del astigmatismo una ligera tendencia a la hipocorrección del
astigmatismo. Es importante resaltar que pese a incluir el análisis de astigmatismo
dentro del artículo, tan solo 46 ojos presentaban astigmatismos bajos por lo que estos
resultados deben ser interpretados con precaución antes de tomar cualquier tipo de
decisión clínica como la creación de un nomograma para la corrección del
astigmatismo.
El segundo de los artículos se centra en la evaluación de la biomecánica corneal
en ojos operados de SMILE. La biomecánica corneal se encuentra relacionada con los
posibles resultados refractivos obtenidos tras la cirugía, de tal manera que la inclusión
de parámetros biomecánicos en los nomogramas de ajuste del error refractivo a tratar
podría ayudar a mejorar la predictibilidad y eficacia del tratamiento. No obstante, la
medida clínica de la biomecánica corneal no se encuentra lo suficientemente madura
como para llevar a cabo este tipo de trabajo de investigación, por lo que el siguiente
paso en esta Tesis doctoral se centró en el estudio del cambio de parámetros del Corvis
ST tras SMILE.
Los resultados mostraron un menor tiempo en alcanzar la primera aplanación
(AT1) y un mayor tiempo en obtener la segunda (AT2), lo que significa que tras la
cirugía SMILE la córnea se aplana con una mayor velocidad y tarda más en volver a su
estado natural. No obstante, no se encontraron diferencias significativas entre los
cambios relativos de tiempos en la primera y segunda aplanación (AT1 – AT1’ vs AT2
– AT2’). De igual forma, encontramos que la amplitud máxima de deformación se
incrementa tras SMILE (DA’ > DA). Cabe destacar en la comparativa de grupos de
baja, media y alta miopía que para los tres parámetros de Corvis ST incluidos en el
análisis (AT1, AT2 y DA) se produce un mayor cambio debido a la cirugía con el
incremento del error refractivo tratado. Este hallazgo derivó en la necesidad de realizar
una comparativa entre grupos considerando el posible efecto que podría tener sobre
cada uno de los parámetros el cambio de espesor corneal que se produce tras la retirada
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del lentículo. En esta segunda comparativa entre los tres grupos de miopía,
considerando el cambio relativo en cada uno de los parámetros en función del cambio
relativo de espesor corneal, no se encontraron diferencias significativas lo cual podría
sugerir que no existen cambios en la rigidez corneal para los diferentes niveles de error
refractivo tratado más allá de los debidos a la presencia de un mayor o menor volumen
de tejido.
Basándonos en estos hallazgos, otra de las cuestiones importantes a resolver fue
si, al igual que ocurría con la ausencia de diferencias entre grupos de refracción más allá
de las explicadas por el espesor corneal, podría darse el caso que las diferencias entre
valores preoperatorios y posoperatorios fuesen debidas exclusivamente al cambio de
espesor corneal. Para resolver esta cuestión se planteó un modelo basado en la amplitud
de deformación máxima cuya hipótesis nula era que la amplitud de deformación
máxima tras la operación (DA’) podía considerarse como la suma entre la amplitud de
deformación máxima antes de la operación más la cantidad de espesor corneal
eliminado (DA+CCT-CCT’). Tras evaluar las diferencias en las medias de amplitud de
deformación posoperatoria y preoperatoria más el espesor eliminado, encontramos que
no podíamos rechazar la hipótesis nula, siendo la amplitud de deformación tras la
cirugía totalmente explicable por la eliminación del espesor corneal y que tras sumar ese
espesor corneal eliminado a la amplitud de deformación preoperatoria, ésta se igualaba
a los valores posoperatorios (DA’ = DA + CCT – CCT’).
El artículo anterior denota la necesidad de emplear nuevos parámetros cuya
variación tras cirugía no se encuentre correlacionada con el cambio de espesor corneal o
que las comparativas entre técnicas se realicen con la inclusión de los cambios relativos
en los parámetros anteriores en función del espesor eliminado. En Septiembre de 2016,
el software comercial del Corvis ST sufrió una importante actualización con la inclusión
de hasta cinco nuevos parámetros que no habían sido considerados en nuestro estudio
anterior. Entre estos parámetros se encuentran la presión intraocular biomecanicamente
corregida (bIOP), el ratio de amplitud de deformación (DAR), el parámetros de rigidez
en la primera aplanación (SP-A1), la inversa del radio integrado en la máxima
concavidad (IR), y el índice de biomecánica corneal (CBI). Dentro de la versión del
software exclusiva con motivos de investigación, recurrimos de igual forma a la medida
de la densitometría dinámica, siendo éste el primer trabajo publicado que recoge
resultados acerca de este parámetro.
Los resultados demostraron que se producían cambios significativos en la bIOP
debido a la cirugía, aunque estos cambios eran menores que en el caso de la medida
convencional de la presión intraocular (IOP) de versiones anteriores del software. Para
sujetos cuya presión intraocular fue medida en la misma franja horaria, las diferencias
preoperatorias y postoperatorias para la IOP fueron de 2.24 ± 1.26 mm Hg, mientras que
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para la IOPb fueron de 0.57 ± 1.27 mmHg, demostrando este último ser un mejor
estimador de la presión intraocular en pacientes operados de SMILE. Además, mientras
que el cambio relativo IOP por la cirugía se correlacionó con el espesor eliminado, esta
correlación no se presentó para el parámetro bIOP.
Todos los parámetros del software comercial incluidos en el estudio cambiaron
de manera significativa tras SMILE. No obstante, cabe destacar que tan solo el
parámetro de rigidez en la primera aplanación (SP-A1) no mostró correlaciones
significativas con la variación del espesor corneal, siendo éste el primer parámetro que
presenta este comportamiento de entre los evaluados de manera previa en nuestras
investigaciones. El parámetro SP-A1 disminuyó de 148.95 ± 12.94 a 142.48 ± 17.31
mmHg/mm indicando que la rigidez de la córnea disminuye tras SMILE con
independencia del espesor eliminado.
Este tercer trabajo recoge el análisis, por primera vez en la literatura científica,
del parámetro de densitometría corneal dinámica, tan solo disponible con motivos de
investigación. Nuestros resultados mostraron que la densitometría máxima alcanzada
durante el pulso de aire y la correspondiente a cada una de las etapas medidas con el
Corvis ST (primera y segunda aplanación, y en el momento de la máxima concavidad)
no diferían entre los valores preoperatorios y posoperatorios con respecto a la media de
los ojos incluidos en el análisis. Se encontraron diferencias entre la densitometría media
alcanzada en cada una de estas etapas, siendo por ejemplo mayor en la segunda que en
la primera aplanación (5.11 ± 1.84). Además, un nuevo signo visible a través del video
de movimiento de la córnea con el pulso de aire fue correlacionado con la cirugía
SMILE. Este signo se corresponde con una línea inclinada brillante que aparece en los
extremos de los dos picos de la córnea cuando esta se encuentra en la fase de máxima
concavidad, esta línea se desplaza desde ambos máximos hacia la periferia conforme la
córnea vuelve a su posición inicial. Especialmente interesante fue que esta línea
apareció en un mayor número de ojos tras la cirugía SMILE. Mientras que 48.8% de los
ojos mostraron este signo antes de la operación, tras la operación el signo apareció en el
72.1% de los casos, siendo el incremento significativo.
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CAPÍTULO 4 CONCLUSIONES Y LÍNEAS FUTURAS
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4.1 Cumplimiento de objetivos
La presente Tesis doctoral finaliza con un repaso al cumplimiento de los objetivos
principales marcados al principio del proyecto. En esta sección haremos un repaso a los
objetivos y describiremos como cada uno de ellos ha sido cubierto a través de cada una de las
tres publicaciones incluidas en el compendio.
Los objetivos planteados al inicio de la Tesis doctoral incluyen:
1. Analizar, en función del error refractivo tratado, los resultados de eficacia, seguridad y
predictibilidad de la técnica SMILE para los primeros casos llevados a cabo por un
cirujano con experiencia en cirugía refractiva, pero no experimentado en la técnica.
2. Evaluar los cambios en los parámetros más reproducibles del Corvis ST en función del
error refractivo tratado y analizar las variaciones de estos parámetros en función del
espesor corneal retirado.
3. Examinar los nuevos parámetros introducidos en la versión del software 1.3r1469
(Septiembre, 2016), los cambios que se producen tras SMILE y la dependencia de
estos parámetros frente a variables de confusión como el espesor corneal.
4. Presentar una nueva hipótesis sobre la densitometría dinámica y su posible relación
con la biomecánica e hidratación corneal.
El primer artículo “Short-term outcomes of small incision lenticule extraction (SMILE)
for low, médium, and high myopia” cubre el primer objetivo de la Tesis. En dicho trabajo se
evaluaron los resultados de seguridad, eficacia y predictibilidad de SMILE a los 6 meses tras la
operación para los primeros 71 casos abordados por el cirujano, autor de la presente Tesis
doctoral. La principal conclusión obtenida de este trabajo es que SMILE cumple los tres
criterios de seguridad, eficacia y predictibilidad inclusive durante la curva de aprendizaje del
cirujano. La novedad de este trabajo frente a trabajos similares previamente publicados es el
análisis en función del error refractivo a tratar, concluyendo que para altas miopías por encima
de -5.00 D es necesario el reajuste del nomograma con el fin de evitar una ligera hipocorrección
de la miopía de -0.50 D.
El segundo artículo “Corneal thickness after SMILE afects Scheimpflug-based dynamic
tonometry” justifica el cumplimiento del objetivo 2. En este trabajo se analizan los cambios en
los parámetros más reproducibles, según la literatura científica previa, del Corvis ST debidos a
la cirugía refractiva SMILE. Todos los parámetros mostraron cambios significativos tras la
cirugía. No obstante, en nuestro trabajo demostramos que todos estos cambios son explicados
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por el espesor de tejido eliminado para corregir la miopía, e incluso que si se adiciona este
espesor a la amplitud de deformación máxima preoperatoria, los resultados ofrecidos por el
instrumento en torno a este parámetro son iguales a los posoperatorios.
Los objetivos 3 y 4 se cumplen mediante el tercer y último artículo, “New parameters
for evaluating corneal biomechanics and intraocular pressure after SMILE by Scheimpflug-
based dynamic tonometry”. Este último trabajo supone una continuación del segundo artículo,
centrándonos en la problemática del espesor corneal como factor de confusión a la hora de
establecer los cambios de rigidez de la córnea debidos al procedimiento. El nuevo índice de la
medida de la presión intraocular biomecánicamente corregida demostró un mejor acuerdo con la
presión intraocular preoperatoria que la medida convencional ofrecida por el instrumento. Todos
los nuevos parámetros biomecánicos mostraron correlación con el cambio de espesor debido al
procedimiento, menos el nuevo índice de rigidez corneal que no mostró dicha correlación. El
nuevo parámetro de densitometría dinámica ofreció interesantes resultados en torno a la
diferencia de densitometría en las tres etapas principales (primera y segunda aplanación, y
máxima deformación) y un nuevo signo que podría estar relacionado con la biomecánica o
hidratación corneal, el cual incrementó su prevalencia tras la cirugía.
4.2 Aportaciones realizadas y líneas futuras de investigación.
Los resultados obtenidos en la presente Tesis indican que un cirujano experimentado en
cirugía refractiva podría alcanzar buenos resultados de seguridad, eficacia y predictibilidad,
incluso durante la curva de aprendizaje. Sin embargo, no podemos afirmar que esto sea
extrapolable para todos los cirujanos, ya que los resultados pertenecen únicamente a los
alcanzados por el autor de esta Tesis. Este trabajo también pone de manifiesto que el
nomograma puede necesitar de un reajuste en altas miopías. En relación a esta necesidad, se
plantea como posible línea futura de investigación el desarrollo de dicho nomograma cubriendo
variables de personalización como la edad, error refractivo, e inclusive datos de biomecánica
corneal, una vez que los parámetros del Corvis ST demuestren su aplicabilidad clínica en este
aspecto.
Esta Tesis doctoral ha servido para poner de manifiesto la necesidad de optimizar los
parámetros del Corvis ST. El propósito de esta optimización es aislar los posibles cambios en la
biomecánica corneal debido a variaciones en la rigidez del tejido, de aquellos producidos por la
modificación en el espesor corneal. La inclusión de los parámetros del Corvis ST en un
nomograma de corrección del error refractivo con la diferenciación anterior supondría que las
variables “error refractivo” y el “parámetro de biomecánica” no estarían correlacionadas entre si
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posibilitando el desarrollo de nomogramas a través de regresiones múltiples. Además,
planteamos como necesarios para la comparativa entre técnicas de cirugía refractiva, los
siguientes dos requerimientos: (1) La inclusión de la diferencia entre valores preoperatorios y
posoperatorios para estudios comparativos y (2) el empleo de índices basados en ratios que
muestren el cambio en cualquiera de los parámetros del Corvis ST en función del espesor
corneal eliminado. El primero de los requerimientos se hace necesario para descartar la presión
intraocular como posible variable de confusión, siempre y cuando, el paciente haya cesado
cualquier tipo de tratamiento que pueda influir en la presión intraocular y los datos sean
tomados durante la misma franja horaria durante el examen preoperatorio y posoperatorio. El
segundo de los puntos es necesario para descartar el espesor corneal como variable de confusión
ya que las diferentes técnicas de cirugía refractiva láser pueden consumir distinto volumen de
tejido para una misma corrección del error refractivo.
Dentro de los nuevos parámetros del Corvis ST, el nuevo índice de rigidez corneal en la
primera aplanación es el único cuya variación no ha demostrado correlación con la variación de
espesor por lo que podría ser utilizado sin necesidad de aplicar el ratio anteriormente
mencionado. No obstante, nuestro estudio es el primero en incluir información relevante a este
parámetro en cirugía refractiva por lo que se requieren más estudios para determinar su validez
cínica. Además, hemos presentado hallazgos especialmente interesantes en relación a la
densitometría corneal dinámica, un parámetro nunca antes reportado en la literatura científica.
Las diferencias entre su valor para las distintas fases de aplanación, el signo de la franja
luminosa que se desplaza hacia la periferia con el pulso de aire, y el incremento de la
prevalencia de este signo tras SMILE deben ser estudiados en profundidad en trabajos futuros y
en condiciones experimentalmente controladas. Esto confirmaría si nuestra hipótesis que
relaciona este signo con la hidratación corneal podría ser cierta.
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