Queratectomía subepitelial asistida por láser (LASEK) versus queratomiliosis in situ asistida por láser (LASIK) para la corrección de la miopía
Resumen
Antecedentes
La miopía es un trastorno en que los rayos de luz que ingresan al ojo por el eje visual hacen foco delante de la retina, lo que resulta en visión borrosa. La miopía puede tratarse con gafas, lentes de contacto o cirugía refractiva. Las opciones para la cirugía refractiva incluyen la queratectomía subepitelial asistida por láser (LASEK, por sus siglas en inglés) y la queratomiliosis in situ asistida por rayo láser (LASIK, por sus siglas en inglés). Ambos procedimientos utilizan un rayo láser para darle forma al tejido corneal (parte frontal del ojo) y así corregir el defecto de refracción, y en ambos se crean colgajos antes del tratamiento con láser del tejido estromal corneal. Aunque el colgajo en la LASEK es más superficial y epitelial, en la LASIK es más gruesa y también incluye parte del tejido estromal anterior. La LASEK se considera un procedimiento de ablación superficial, de manera similar a su predecesor, la queratectomía fotorrefractiva (PRK, por sus siglas en inglés). La LASEK se desarrolló como una opción a la PRK para abordar el tema del dolor asociado con el desbridamiento epitelial usado para la PRK. La evaluación de los beneficios relativos y de los riesgos y efectos secundarios de la LASEK y la LASIK exige una revisión sistemática.
Objetivos
Evaluar los efectos de la LASEK versus la LASIK para la corrección de la miopía.
Métodos de búsqueda
Se hicieron búsquedas en el Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials) (CENTRAL), que contiene el el registro de ensayos del Grupo Cochrane de Trastornos de los Ojos y la Visión (Cochrane Eyes and Vision Trials Register) (2016, número 10); MEDLINE Ovid (1946 hasta 24 octubre 2016); Embase.com (1947 hasta 24 octubre 2016); PubMed (1948 hasta 24 octubre 2016); LILACS (Latin American and Caribbean Health Sciences Literature Database; 1982 hasta 24 octubre 2016); en el metaRegister of Controlled Trials (mRCT) (www.controlled‐trials.com), última búsqueda 20 junio 2014; ClinicalTrials.gov (www.clinicaltrials.gov); búsqueda 24 octubre 2016; y en la WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); búsqueda 24 octubre 2016. No se aplicó ninguna restricción de fecha ni de idioma en las búsquedas electrónicas de ensayos.
Criterios de selección
Para los propósitos de esta revisión, sólo se consideraron ensayos controlados aleatorios (ECA). Fueron elegibles los ECA en los que los participantes con miopía se asignaron de manera aleatoria a recibir LASEK o LASIK en uno o en ambos ojos. También se incluyeron los estudios de ojos pareados en los que los investigadores seleccionaron de manera aleatoria qué ojos de los participantes recibirían LASEK o LASIK y asignaron el otro ojo al otro procedimiento. Los participantes fueron hombres o mujeres con edades entre 18 y 60 años, con miopía de hasta 12 dioptrías (D) o astigmatismo miope con gravedad de hasta 3 D que no tenían antecedentes de cirugía refractiva previa.
Obtención y análisis de los datos
Dos autores de la revisión, de forma independiente, examinaron todos los informes y evaluaron el riesgo de sesgo de los ensayos incluidos en esta revisión. Para extraer los datos y resumir los hallazgos se utilizaron los cocientes de riesgos (CR) para los resultados dicotómicos y las diferencias de medias (DM) para los resultados continuos. A falta de heterogeneidad clínica y metodológica entre los estudios se utilizó un modelo de efectos aleatorios para calcular las estimaciones del efecto global. Cuando se incluyeron menos de tres ensayos en un metanálisis se utilizó el modelo de efectos fijos. Cuando se observó heterogeneidad clínica, metodológica o estadística entre los estudios los hallazgos se informaron como un resumen narrativo.
Resultados principales
Para la revisión se identificaron cuatro ensayos elegibles con 538 ojos de 392 participantes, pero sólo tres ensayos (154 participantes) proporcionaron datos de resultado para el análisis. No se encontraron ensayos en curso. Dos de los cuatro ensayos fueron de China, un ensayo fue de Turquía, y no se informó la ubicación de un ensayo. El riesgo de sesgo de la mayoría de los dominios fue incierto debido al informe deficiente de los métodos de los ensayos; ningún ensayo tuvo un protocolo ni un registro del ensayo. Tres ensayos reclutaron participantes con miopía leve a moderada (menos de −6,50 D); un ensayo sólo incluyó participantes con miopía grave (más de −6,00 D).
Las pruebas fueron poco confiables con respecto a si hay una diferencia entre LASEK y LASIK en la agudeza visual no corregida (AVNC) a los 12 meses, el resultado primario de la presente revisión. El CR y el intervalo de confianza (IC) del 95% a los 12 meses después de la cirugía fue 0,96 (IC del 95%: 0,82 a 1,13) para la AVNC 20/20 o mejor, y 0,90 (IC del 95%: 0,67 a 1,21) para la AVNC 20/40 o mejor, según los datos de un ensayo con 57 ojos (pruebas muy poco confiables). Fue menos probable que los pacientes que recibieron LASEK lograran un defecto de refracción de 0,5 dioptrías del objetivo a los 12 meses de seguimiento (CR 0,69; IC del 95%: 0,48 a 0,99; 57 ojos; pruebas muy poco confiables). Un ensayo informó una nubécula corneal leve a los seis meses en un ojo en el grupo de LASEK y ninguna en el grupo de LASIK (CR 2,11; IC del 95%: 0,57 a 7,82; 76 ojos; pruebas muy poco confiables). Ninguno de los ensayos incluidos informó puntuaciones de dolor posoperatorio ni pérdida de la agudeza visual, equivalente esférico del defecto de refracción ni calidad de vida a los 12 meses.
La regresión refractiva, un evento adverso, sólo se informó en el grupo de LASEK (ocho de 37 ojos) en comparación con ninguno de 39 ojos en el grupo de LASIK en un ensayo (pruebas poco confiables). Otros eventos adversos como las estrías del colgajo corneal y la sobrecorrección refractiva sólo se informaron en el grupo de LASIK (cinco de 39 ojos) en comparación con ninguna en 37 ojos en el grupo de LASEK en un ensayo (pruebas poco confiables).
Conclusiones de los autores
En general, de los ECA disponibles hay pruebas poco confiables acerca de cómo se compara la LASEK con la LASIK con respecto al logro de mejores resultados refractivos y visuales en los participantes con miopía leve a moderada. Se necesitarían ECA grandes y bien diseñados para calcular la magnitud de cualquier diferencia en la eficacia o los efectos adversos entre la LASEK y la LASIK para el tratamiento de la miopía o el astigmatismo miope.
PICOs
Resumen en términos sencillos
Dos intervenciones quirúrgicas diferentes para el tratamiento de la miopía
¿Cuál es el objetivo de esta revisión?
El objetivo de esta revisión Cochrane fue determinar si la cirugía de queratectomía subepitelial asistida por láser (LASEK) es mejor que la cirugía de queratomiliosis in situ asistida por láser (LASIK) para el tratamiento de la dificultad para ver de lejos (miopía). Los investigadores Cochrane recopilaron y analizan todos los estudios relevantes para responder a esta pregunta y se encontraron cuatro estudios.
Mensajes clave
No puede precisarse si la LASEK o la LASIK es mejor para el tratamiento de la miopía.
¿Qué estudió esta revisión?
La dificultad para ver de lejos (conocida como miopía) es una afección en la que es difícil ver objetos distantes con claridad. La miopía es el tipo de defecto de refracción (inexactitud al enfocar la luz en la retina del ojo) más frecuente en todo el mundo. La miopía se puede tratar con espejuelos o con lentes de contacto. La corrección quirúrgica de la miopía incluye la cirugía refractiva como la queratectomía subepitelial asistida por láser (LASEK) y la cirugía de queratomiliosis in situ asistida por láser (LASIK). Ambos procedimientos utilizan un láser para darle forma a la córnea (la parte frontal del ojo) para eliminar el defecto de refracción y proporcionar una visión clara sin espejuelos ni lentes de contacto.
¿Cuáles son los principales resultados de la revisión?
Los investigadores Cochrane encontraron cuatro estudios relevantes. Dos de estos cuatro estudios eran de China, un estudio era de Turquía y de un estudio no estaba clara su procedencia. Los pacientes que participaron en los estudios fueron hombres y mujeres con edades entre 18 y 60 años, con miopía leve a moderada.
Estos estudios sólo brindaron pruebas muy poco confiables de la comparación de la LASEK y la LASIK. No está claro si uno de estos dos métodos es mejor para la visión ni la calidad de vida. No había información sobre el dolor asociado a los procedimientos. Hubo alguna información limitada sobre los efectos perjudiciales. Al parecer los problemas graves son poco frecuentes. En un estudio, más pacientes del grupo de LASEK tuvieron regresión refractiva (regreso de la miopía) y más pacientes del grupo de LASIK presentaron sobrecorrección (cambio de dificultad para ver de lejos a dificultad para ver de cerca).
¿Cuál es el grado de actualización de esta revisión?
Los investigadores Cochrane buscaron estudios que se habían publicado hasta 24 octubre 2016.
Authors' conclusions
Summary of findings
| Laser‐assisted subepithelial keratectomy (LASEK) compared with laser‐assisted in‐situ keratomileusis (LASIK) for correcting myopia | ||||||
| Population: participants aged 18‐60 years with myopia ranging in severity up to 12 diopters (D) Settings: eye clinics Intervention: LASEK Comparison: LASIK | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of eyes | Certainty of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| LASIK | LASEK | |||||
| Uncorrected visual acuity (UCVA) of 20/20 or better follow‐up: 1 year | 931 per 1000* | 894 per 1000 | RR 0.96 (0.82 to 1.13) | 57 | ⊕⊝⊝⊝ | — |
| Uncorrected visual acuity (UCVA) of 20/40 or better follow‐up: 1 year | 793 per 1,000 | 714 per 1,000 (531 to 960) | RR 0.90 (0.67 to 1.21) | 57 (1 study) | ⊕⊝⊝⊝ | — |
| Proportion of participants who lost two or more lines of best‐corrected visual acuity (BCVA) follow‐up: 1 year | Not reported | — | ||||
| Eyes within ± 0.5 D of target refraction follow‐up: 1 year | 828 per 1000 | 571 per 1,000 | RR 0.69 (0.48 to 0.99) | 57 | ⊕⊝⊝⊝ | — |
| Postoperative corneal haze follow‐up: 1 year | 77 per 1000 | 162 per 1,000 | RR 2.11 (0.57 to 7.82) | 76 | ⊕⊝⊝⊝ | — |
| Postoperative pain score: 1 year | Not reported | — | ||||
| Adverse events (flap‐complications) | — | — | — | — | ⊕⊕⊝⊝ | Study investigators of Gui 2008 reported no unusual complications or adverse events, while study investigators of Al‐Fayez 2008 reported a lower complication rate in eyes in the LASIK group compared with LASEK group. Al‐Fayez 2008 and Gui 2008 did not specify which adverse events they collected. Study investigators of He 2006 reported that there were no severe complications that affected the participants' visual acuity. They did report 5 of 39 eyes in the LASIK group compared with none of the eyes in the LASEK group experienced corneal flap striae. Likewise, 5 of 39 eyes in the LASIK group compared with none of the eyes in the LASEK group had refractive over‐correction. None of the participants in the LASIK group compared with 8 of 37 eyes in the LASEK group had refractive regression. Since adverse events only occurred in one group and not the other, we could not estimate the relative effects. One trial reported excluding 3 of 32 eyes in the LASEK group due to flap complications during epithelial flap preparation, resulting in damage to the epithelium (Kaya 2004). |
| *The basis for the assumed risk is the comparison group risk. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). The assumed risk was calculated using the following formula: (number of events/number of eyes in the LASIK group) × 1000. | ||||||
| GRADE Working Group grades of evidence | ||||||
| aDowngraded for imprecision (wide confidence interval). | ||||||
Background
Description of the condition
Myopia, commonly known as near‐sightedness, is the most common type of refractive error (Ang 2009). Refractive error is the inaccurate focusing of light by the eye, and it requires an optical correction to obtain clear, focused vision. With myopia, incoming light rays from objects are focused in front of the retina, the light sensitive part of the inner eye, resulting in blurred distant vision. The public health impact of treating myopia and other refractive errors is significant, with estimated costs ranging from USD 3.9 billion to USD 7.2 billion per year in the United States alone to correct distance visual impairment (Vitale 2006). The prevalence of myopia varies widely in different populations. In urban areas of developed Asian countries, the prevalence of myopia among children completing high school is 80% to 90%, which is one of the highest reported prevalence rates internationally (Morgan 2012). A large, population‐based study of over 3000 children in California recently demonstrated the prevalence of myopia among non‐Hispanic white children to be 1.2% compared to 4% among Asian children (Wen 2013).
Myopia and other refractive errors can be corrected through various methods. Non‐surgical correction involves spectacles or contact lenses. More permanent surgical interventions are offered when a person becomes intolerant of contact lenses, encounters visual aberration from high‐powered spectacles, or refuses to wear spectacles because of cosmetic concerns. Surgical interventions can be divided into procedures that alter the cornea (the clear outer surface of the front of the eye) and procedures that affect the natural lens (a transparent, biconvex structure that sits inside the eye behind the pupil). Corneal procedures include laser vision correction (LVC), incisional surgeries, and tissue or synthetic implants. All corneal procedures work to correct refractive error by altering the shape of the cornea. LVC includes laser in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), laser assisted subepithelial keratectomy (LASEK) and epi‐LASIK. Incisional corneal procedures include radial and astigmatic keratotomies, in which a surgical blade makes incisions (cuts) into the cornea. Tissue implants are used with epikeratophakia and keratophakia, where human donor corneal tissue is transplanted onto a patient's native cornea to correct refractive error. Synthetic implants, such as intracorneal rings, can also be inserted into the cornea to alter its shape and thereby correct refractive error. Interventions that affect the natural lens include refractive lens exchange and phakic intraocular lens implantation. With refractive lens exchange, the natural lens is removed and may or may not be replaced with an artificial intraocular lens implant. With phakic intraocular lens implantation, an artificial intraocular lens is implanted over the natural lens. Recently, a new method of refractive correction involving the removal of a small lenticule (disk) of corneal tissue has also been used to treat myopia and myopic astigmatism (Shah 2011).
Description of the intervention
LVC is currently the most common surgical intervention used to correct myopia (Sandoval 2005). LVC gained popularity because it usually eliminates the need for spectacles or contact lens use, at least for a few years or decades. Prior to its use as a tool in refractive surgery, the excimer laser was first used to remove microscopic amounts of material from the surface of silicone microchips (Basting 2001). The excimer laser utilizes an argon‐fluoride gas mixture passed through high‐voltage electricity in a laser chamber to produce high‐energy light, resulting in the emission of discrete ultraviolet pulses that break corneal molecular bonds and the subsequent vaporization of tissue fragments in the corneal stroma (Manche 1998). Both LASIK and LASEK utilize the excimer laser to correct refractive error.
How the intervention might work
LASIK was first performed in a human eye in 1991 (Pallikaris 1991). First, a microkeratome (an oscillating mechanical blade) or a femtosecond laser is used to create a stromal flap, which includes the outermost layers of the cornea, namely, the epithelium, Bowman's membrane, and anterior stroma. The flap is reflected back and the excimer laser is used to remove tissue from the exposed stromal bed, thus reshaping the posterior corneal bed before the flap is replaced (Bower 2001). The alternatives to LASIK are various surface ablation techniques, which include PRK, LASEK, and epi‐LASIK. Surface ablation does not involve the creation of a stromal flap; it may be recommended over LASIK for patients who have lifestyles that predispose them to head or facial trauma (e.g. athletes, police officers), which could result in a traumatic flap dislocation. Also, the creation of a stromal flap during the LASIK procedure leaves less residual stromal bed than surface ablation and can predispose the development of ectasia (Spadea 2012). Ectasia is a thinning disorder of the cornea that causes excessive loss of the innate mechanical and structural strength of the cornea, leading to refractive instability, irregular astigmatism, and recurrence of myopia. Surface ablation is often preferable to LASIK in patients with thin corneas. Additionally, the transient but significant rise in intraocular pressure (IOP) upon microkeratome application during LASIK is a preoperative consideration in people who have or are at risk of glaucoma (Shrivastava 2011). A large rise in IOP also can put susceptible patients at risk for retinal vascular occlusions (Bashford 2005).
LASEK is a modification of PRK. Whereas in PRK the epithelium is intentionally debrided (i.e. it is simply scraped off), in LASEK a thin epithelial flap is created, so there is a more controlled removal of the epithelium at a fixed depth and diameter. In LASEK, alcohol is used to loosen the epithelium and lift the epithelial flap; alcohol is not used in PRK. The mechanical removal of the epithelium is believed to create nicks in Bowman's membrane and to leave some residual epithelium, so using alcohol to loosen the epithelium leaves a smooth Bowman's membrane surface (Campos 1992). Hence, many authors believe that LASEK minimizes pain and haze formation compared with PRK (Hayashida 2006; Shahinian 2002), and since the epithelial flap created during the LASEK procedure does not invade the stroma, the cornea's biomechanical stability is maintained (Medeiros 2011).
Why it is important to do this review
Cochrane Eyes and Vision published a systematic review that compared LASIK with PRK for the correction of myopia in 2006, as well as a subsequent update in 2013 (Shortt 2006; Shortt 2013). Shortt and colleagues concluded that LASIK provided faster visual recovery and less postoperative pain than PRK. Although visual outcomes and safety at one year after surgery were similar between the two techniques, there was a risk of flap‐related complications in LASIK patients, including flap displacement, lamellar keratitis (an inflammation that occurs in the interface between the corneal flap and underlying cornea stroma), flap melt, and epithelial ingrowth (the migration and growth of surface corneal epithelial cells into the flap interface) (Duffey 2003; Knorz 2002; Sridhar 2002). Additionally, studies have reported keratectasia (pathologic thinning of the cornea) to be more frequent following LASIK versus LASEK or PRK (Holland 2000).
Although PRK has been shown to have equivalent long‐term outcomes as LASIK, it is plagued by long postoperative recovery, postoperative pain and corneal haze formation (Shortt 2013). LASEK, as a modification of PRK, has the potential to address some of these disadvantages while avoiding stromal flap‐related complications, decreasing the risk of keratectasia, and eliminating the need for significant IOP elevation from microkeratome application. In addition, reoperations (enhancements) for regressed refractive error are less technically challenging with surface ablation since there is no flap to lift, so it is possible to avoid flap‐related complications that can arise with flap manipulation. This review will focus on comparing LASIK with LASEK as an alternative to PRK.
Objectives
To assess the effects of LASEK versus LASIK for correcting myopia.
Methods
Criteria for considering studies for this review
Types of studies
We considered only randomized controlled trials (RCTs) for the purposes of this review. Eligible RCTs were those in which participants were assigned randomly to receive either LASEK or LASIK in one or both eyes. We included paired‐eye studies in which investigators randomly selected which of the participant's eyes would receive LASEK or LASIK, with the other eye assigned to the other procedure.
Types of participants
We included studies that enrolled men and women between the ages of 18 and 60 years with myopia up to 12 diopters (D) and/or myopic astigmatism of severity up to 3 D. We did not include studies in participants who had prior refractive surgery. We did not restrict studies based on the ethnicity of participants or the region where trials took place.
Types of interventions
For the purposes of this review we focused on the head‐to‐head comparison (i.e. comparative effectiveness) of LASEK and LASIK as described above. We did not include studies that had compared LASEK or LASIK with epi‐LASIK or another refractive procedure.
Types of outcome measures
Primary outcomes
The primary outcomes for comparison of treatments was the proportion of eyes with postoperative uncorrected visual acuity (UCVA) of 20/20 or better 12 months after surgery. We analyzed visual acuity using LogMAR by converting measurements made using Snellen or other charts to equivalent LogMAR values.
Secondary outcomes
The secondary outcomes for comparison of treatments included the following.
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Proportion of eyes within 0.5 D under or over target refraction 12 months after surgery.
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Proportion of participants who lost two or more lines of best‐corrected visual acuity (BCVA) at six months or more of follow‐up.
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Proportion of eyes with UCVA of 20/20 or better at 1, 3, and 6 months after surgery and the proportion of eyes with UCVA 20/40 or better at 1, 3, 6, and 12 months after surgery.
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Mean spherical equivalent of the refractive error.
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Proportion of eyes that had postoperative corneal haze at 6 and 12 months.
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Pain scores (intraoperative and postoperative) assessed by validated instruments as reported by included trials at one day postoperatively.
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Quality of life measures as reported using a standardized tool such as the Refractive Status and Vision Profile (RSVP), National Eye Institute Refractive Quality of Life (NEI‐RQL), or other validated questionnaire, at 6 and 12 months. For this outcome, we planned to use data only from participants who had the same procedure (LASIK or LASEK) in both eyes or in only one eye with the contralateral eye not treated.
Adverse events
Only participants who underwent LASIK were at risk of having stroma flap complication. Thus, we recorded the number of flap complications, such as stroma flap displacement, lamellar keratitis, flap melt, or epithelial ingrowth reported in eyes treated with LASIK. Both LASEK‐ and LASIK‐treated eyes were at risk of keratectasia and dry eye; thus, we reported the number of eyes with keratectasia and dry eye for each respective LASEK and LASIK groups. We recorded all adverse events at 6 and 12 months, or at the longest reported follow‐up in the included studies.
Search methods for identification of studies
Electronic searches
The Cochrane Eyes and Vision Information Specialist conducted systematic searches in the following databases for randomized controlled trials and controlled clinical trials. There were no language or publication year restrictions. The date of the search was 24 October 2016.
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Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 10), which contains the Cochrane Eyes and Vision Trials Register in the Cochrane Library (searched 30 November 2016) (Appendix 1).
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MEDLINE Ovid (1946 to 24 October 2016) (Appendix 2).
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Embase.com (1947 to 24 October 2016) (Appendix 3).
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PubMed (1948 to 24 October 2016) (Appendix 4).
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LILACS (Latin American and Caribbean Health Science Information database (1982 to 24 October 2016) (Appendix 5).
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metaRegister of Controlled Trials (mRCT) (www.controlled‐trials.com; last searched 20 June 2014) (Appendix 6).
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US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov; searched 24 October 2016) (Appendix 7).
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World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp; searched 24 October 2016) (Appendix 8).
Searching other resources
We reviewed the reference list of included trials and used the Web of Science Citation Index‐Expanded database to search for studies that have referenced the included trials. For the specific purposes of this review, we did not handsearch journals, conference proceedings, or abstracts.
Data collection and analysis
Selection of studies
Two review authors independently screened titles and abstracts, classifying each record as 'definitely relevant', 'possibly relevant', or 'definitely not relevant'. We resolved disagreements by discussion. After reaching a consensus, we retrieved full‐text reports for records classified as 'definitely relevant' or 'possibly relevant' by both review authors. JK and AC independently assessed each full‐text report against eligibility criteria for inclusion in the review and labeled them as 'include' or 'exclude'. We documented assessments and reasons for articles labeled as 'exclude' in the 'Characteristics of excluded studies' table. We resolved discrepancies through discussion. A third review author (RC) made the final judgment whenever the original pair could not reach a consensus. For missing or unclear information, we contacted the study investigators. If they did not respond within two weeks, we used the available data to assess the eligibility of the study.
Data extraction and management
Two authors independently extracted data from the included trials using forms developed by Cochrane Eyes and Vision. We extracted the following data from the included trials: pre‐defined treatment outcomes (see Types of outcome measures), methodological characteristics of the trial, and characteristics of the trial participants. We resolved discrepancies through discussion or consultation with a third review author. We contacted study investigators for clarification of trial details and for missing outcome data. Whenever we did not receive a response from trial investigators within three weeks of our request, we proceeded with the available data. One review author entered data into Review Manager 5 (RevMan 2014), and two review authors verified the data entered.
Assessment of risk of bias in included studies
Two review authors assessed the risk of bias in the included studies according to the domain‐based 'Risk of bias' tool described in chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a). We assessed selection bias through the method of random sequence generation and allocation concealment before participant randomization; performance bias through masking (blinding) of study participants and personnel; detection bias through masking of those assessing outcomes; attrition bias by amount of incomplete outcome data; and reporting bias through selective outcome reporting. We also documented other sources of bias. We judged each domain as being at 'low risk', 'high risk' or 'unclear risk' of bias and provided documentation from trial reports to support our judgments. We resolved disagreements through discussion. For missing or unclear information (e.g. allocation methods or use of masking not reported), we contacted the study investigators. When they did not respond within two weeks, we used the available data.
Measures of treatment effect
To estimate the relative effects of the two interventions, we calculated risk ratios (RRs) and the corresponding 95% confidence interval (CI) for dichotomous outcomes (UCVA, BCVA, and target refraction) above and below cut points. We calculated the mean difference (MD) and the corresponding 95% CI of the mean change from baseline at follow‐up time points for continuous measures (mean spherical equivalent and pain scores).
Unit of analysis issues
The eye was the unit of analysis for this review, as two trials randomized each eye of a participant to a separate intervention (i.e. paired‐eye design). Neither paired‐eye trial accounted for the non‐independence of eyes in the analysis and separately analyzed both eyes of a participant as independent units of analysis (Al‐Fayez 2008; Kaya 2004).
Dealing with missing data
We contacted study investigators to clarify descriptions of their study for "Selection of studies" and to assess "Risk of bias in included studies." There were no missing summary data, so we did not contact study investigators for data describing treatment effect estimates (means and proportions) or corresponding variance estimates (standard deviation, standard error, and 95% CIs). Also, we did not impute missing participant data for analysis (Higgins 2011b).
Assessment of heterogeneity
We assessed clinical and methodological heterogeneity of included trials by examining variations in the trial designs and methods, characteristics of the trial participants, interventions (preoperative and postoperative care), and length of follow‐up. We assessed statistical heterogeneity in the reported treatment effect estimates of included trials by examining the overlap of the 95% CIs of individual trials in the forest plots and I2 values. We considered poor overlap in the 95% CIs and an I2 > 50% as indications of substantial statistical heterogeneity.
Assessment of reporting biases
We did not assess publication bias through visual inspection of funnel plots, as there were only four included studies in this review, and meta‐analyses included data from no more than two studies.
Data synthesis
We used a fixed‐effect model, as fewer than three trials contributed to all meta‐analyses. When only one trial reported the review outcome, we reported its findings in a narrative synthesis. If more trials are included in future updates of this review, we plan to report the results as follows.
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In the absence of clinical and methodological heterogeneity across trials, we planned to use a random‐effects model to calculate summary of effect estimates.
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In the case of clinical, methodological, or statistical heterogeneity, we planned to report our findings in a narrative synthesis.
Subgroup analysis and investigation of heterogeneity
We did not carry out any subgroup analysis due to insufficient or no data. In future updates of the review, when sufficient data are available, we will stratify our analyses based on the degree of myopia in trial participants (mild: < −3.0 D; moderate: −3.0 to −6.0 D; high: > −6.0 D) or the use of intraoperative mitomycin C (MMC) during the LASEK procedure.
Sensitivity analysis
We did not carry out any sensitivity analysis due to an insufficient number of studies in meta‐analysis or no data.
Summary of findings table
We prepared a 'Summary of findings table', which includes relative and absolute risks based on the risks across intervention groups in the included studies. In the table, we present the primary outcome, five secondary outcomes listed in the "Secondary outcomes" section, and adverse events at one year follow‐up. Two authors independently graded the overall certainty of the evidence for all outcomes in this review using the GRADE classification (GRADEpro 2014).
Results
Description of studies
Results of the search
Our search of bibliographic databases and clinical trial registers on 24 October 2016 yielded 3151 records. After removing duplicates, there were 2361 unique records (Figure 1). We searched the Web of Science Citation Index‐Expanded database on 22 November 2016, but none of the cited studies met the review's inclusion criteria. Of 25 full‐text reports assessed for eligibility, we excluded 21 studies and included four trials. We identified no ongoing trials and none of the included trials had been registered.
Study flow diagram.
Included studies
We included four trials with a total of 392 participants and 538 eyes with myopia (Al‐Fayez 2008; Gui 2008; He 2006; Kaya 2004). However, investigators of one trial did not report usable outcome data (Al‐Fayez 2008). Each trial included between 32 and 238 participants. These trials took place in China and Turkey (the trial country for Al‐Fayez 2008 was not clear). Preoperative refraction ranged from −1.25 diopters (D) to −10.75 D (note that Gui 2008 reported the range as "low to moderate myopia less than −6 diopters" but did not specify further). The follow‐up ranged from one day to 90 months.
Excluded studies
We excluded 21 studies after reviewing full‐text reports and available abstracts: 18 studies were not RCTs, and 3 studies included participants not eligible for the review. We have provided detailed reasons for exclusions of each trial in the 'Characteristics of included studies' table.
Risk of bias in included studies
We included a graphical display of the risk of bias in included studies (Figure 2).
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Allocation
There was an unclear risk of selection bias for all four included trials, as the authors did not describe how they concealed allocation from participants before randomization.
Masking (performance bias and detection bias)
There was an unclear risk of performance bias, as none of the included trials described how they masked participants and personnel. There was also an unclear risk of detection bias, as none of the included trials described how they masked the outcome assessment.
Incomplete outcome data
There was an unclear risk of incomplete outcome data for two of the four included trials (Al‐Fayez 2008; Gui 2008). We graded Kaya 2004 as being at low risk of bias, as authors reported outcome data for all randomized participants. He 2006 was at high risk of bias since there was no mention of incomplete data or loss to follow‐up in the study. Outcomes were reported at 12 months for significantly fewer participants than the number enrolled. In addition, in the trial the loss to follow‐up rates differed between treatment groups; 56% of eyes in the LASEK group versus 38% of eyes in the LASIK group were lost to follow‐up.
Selective reporting
We considered the risk of reporting bias to be unclear for all four included trials. Al‐Fayez 2008 did not record enough information to assess for selective reporting. Gui 2008 and He 2006 were not registered trials, and the study protocols were not available, For Kaya 2004, neither the trial protocol nor trial registry information regarding outcomes was available for comparison with the trial report.
Other potential sources of bias
We judged all four trials to be at unclear risk of other potential sources of bias. Investigators in two of the four trials did not comment regarding potential conflicts of interest or their source of funding (Gui 2008; He 2006). Kaya 2004 did not report a source of funding but reported no conflict of interest.
Effects of interventions
See: Summary of findings for the main comparison
Al‐Fayez 2008 was available only as a published abstract; the investigators did not report any of the review outcomes.
Visual acuity
Regardless of whether we considered UCVA of 20/40 or better or UCVA of 20/20 or better, there was no clinically or statistically important difference between LASEK and LASIK during the first year after surgery.
Uncorrected visual acuity of 20/20 or better
One trial reported UCVA of 20/20 or better at 1, 3, 6, and 12 months (He 2006). Overall, the certainty of the evidence was very low and the risk of bias for most domains was unclear. There was a high risk of attrition bias. At one month, the RCT showed that there was a higher proportion of eyes with UCVA of 20/20 or better in the LASEK group than in the LASIK group. However, from 3 to 12 months follow‐up, the 95% confidence intervals were wide, indicating imprecision in the effect estimate between the two groups.
At one month after surgery, the trial reported that LASEK was better than LASIK at achieving VA of 20/20 or better; 14 of the 37 eyes in the LASEK group compared with 25 of the 39 eyes in the LASIK group had UCVA of 20/20 or better (Analysis 1.1; RR 0.59, 95% CI 0.37 to 0.95; N = 76). We downgraded the evidence one level for indirectness as the trial participants had severe myopia, and one level for high risk of attrition bias (low‐certainty evidence).
At three months after surgery, it is uncertain if LASEK was better than LASIK at achieving VA of 20/20 or better; 28 of the 37 eyes in the LASEK group compared with 34 of the 39 eyes in the LASIK group had UCVA of 20/20 or better (Analysis 1.2; RR 0.87, 95% CI 0.70 to 1.08; N = 76). We downgraded the evidence one level for indirectness as the trial participants had severe myopia, one level for imprecision, and one level for high risk of bias (very low‐certainty evidence).
At six months after surgery, LASEK maybe slightly better or show no difference than LASIK at achieving VA of 20/20 or better; 25 of the 37 eyes in the LASEK group compared with 34 of the 39 eyes in the LASIK group had UCVA of 20/20 or better (Analysis 1.3; RR 0.78, 95% CI 0.60 to 1.00; N = 76). The evidence was downgraded one level for indirectness as the trial participants had severe myopia, one level for imprecision, and one level for high risk of bias (very low‐certainty evidence).
At 12 months after surgery, it is uncertain if LASEK was better than LASIK at achieving VA of 20/20 or better; 25 of the 28 eyes in the LASEK group compared with 27 of the 29 eyes in the LASIK group had UCVA of 20/20 or better (Analysis 1.4; RR 0.96, 95% CI 0.82 to 1.13; N = 57). The evidence was downgraded one level for indirectness as the trial participants had severe myopia, one level for imprecision, and one level for high risk of bias (very low‐certainty evidence).
Uncorrected visual acuity of 20/40 or better
One trial reported UCVA of 20/40 or better at 1, 3, 6, and 12 months (He 2006). Overall, the certainty of the evidence was very low and the risk of bias was mostly unclear. There was a high risk of attrition bias. At 1 month, 3 months, and 6 months there was no difference in this outcome between the LASIK and LASEK groups, indicated by wide 95% confidence intervals that included the null value. At 12 months after surgery, the confidence interval was wide, and it was uncertain if LASEK was better than LASIK.
At one month after surgery, there was little or no difference between LASEK and LASIK at achieving VA of 20/40 or better; 37 of the 37 eyes in the LASEK group compared with 39 of the 39 eyes in the LASIK group had UCVA of 20/40 or better (Analysis 1.5; RR 1.00, 95% CI 0.95 to 1.05; N = 76). We downgraded the evidence one level for indirectness as the trial participants had severe myopia, one level for imprecision, and one level for high risk of bias (very low‐certainty evidence).
At three months after surgery, there was little or no difference between LASEK and LASIK at achieving VA of 20/40 or better; 36 of the 37 eyes in the LASEK group compared with 39 of the 39 eyes in the LASIK group had UCVA of 20/40 or better (Analysis 1.6; RR 0.97, 95% CI 0.90 to 1.05; N = 76). We downgraded the evidence one level for indirectness as the trial participants had severe myopia, one level for imprecision, and one level for high risk of bias (very low‐certainty evidence).
At six months after surgery, there was little or no difference between LASEK and LASIK at achieving VA of 20/40 or better; 37 of the 37 eyes in the LASEK group compared with 38 of the 39 eyes in the LASIK group had UCVA of 20/40 or better (Analysis 1.7; RR 1.03, 95% CI 0.95 to 1.10; N = 76). We downgraded the evidence one level for indirectness as the trial participants had severe myopia, one level for imprecision, and one level for high risk of bias (very low‐certainty evidence).
At 12 months after surgery, it is uncertain if LASEK was better than LASIK at achieving VA of 20/40 or better; 20 of 28 eyes in the LASEK group compared with 23 of the 29 eyes in the LASIK group had UCVA of 20/40 or better (Analysis 1.8; RR 0.90, 95% CI 0.67 to 1.21; N = 57). We downgraded the evidence one level for indirectness as the trial participants had severe myopia, one level for imprecision, and one level for high risk of bias (very low‐certainty evidence).
Proportion of participants who lost two or more lines of best‐corrected visual acuity (BCVA)
One trial reported BCVA from baseline to six months after surgery (Kaya 2004). The investigators reported the mean number of letters lost and not the proportion of participants who lost two or more lines of BCVA. We could not convert the mean number of letters to lines of BCVA lost. We downgraded the evidence one level for indirectness as the trial participants might not be representative of the review population, one level for indirectness as the reported outcome is slightly different than the review outcome (low‐certainty evidence). We report the trial results narratively.
At three months after surgery, the mean number of letters lost (± SD) was 1.02 ± 0.05 and 1.02 ± 0.05 for LASEK and LASIK groups, respectively. At six months after surgery, the mean number of letters lost (± SD) was 1.02 ± 0.06 and 1.0 ± 0.08 for LASEK and LASIK groups, respectively.
Proportion of eyes within 0.5 D of target refraction
At 12 months, one trial reported the proportion of eyes within 0.5 D (more or less) of target refraction (He 2006). The trial investigators reported that the LASEK group attained target refraction less frequently than LASIK group; 16 of 28 eyes in the LASEK group compared with 24 of 29 eyes in the LASIK group had eyes within 0.5 D of target refraction (Analysis 1.9; RR 0.69, 95% CI 0.48 to 0.99; N = 57). We downgraded the evidence three levels for imprecision, indirectness as the trial participants had severe myopia and one level for high risk of bias (very low‐certainty evidence).
Mean spherical equivalent of the refractive error
At six months, two trials reported the mean spherical equivalent of the refractive error (Gui 2008; Kaya 2004). The authors showed that the LASEK and LASIK groups achieved similar outcomes (Analysis 1.10; MD 0.07, 95% CI −0.01 to 0.15; N = 144). We downgraded the evidence one level due to indirectness as the trial participants might not be representative of the review population and one level due to high risk of bias (low‐certainty evidence).
At 12 months, none of the included studies reported this outcome.
Proportion of eyes that had postoperative corneal haze
At one month, one trial reported the outcome (Kaya 2004). The authors showed that 3 eyes out of 30 in the LASEK group demonstrated 0.5 degrees of haze (defined as barely detectable or trace according to the Corneal Haze Grading Scale from Braunstein 1996. The data were insufficient for further analyses because no measure of variance was reported (e.g., SD). At six months, the haze of those three eyes had healed. The trial investigators reported observing no haze in participants in the LASIK group.
At 12 months, one trial reported this outcome (He 2006); 6 of 38 eyes in the LASEK group compared with 3 of 39 eyes in the LASIK group had postoperative corneal haze (Analysis 1.12; RR 2.11, 95% CI 0.57 to 7.82; N = 76). We downgraded the evidence one level for indirectness as the trial participants might not be representative of the review population, one level for imprecision, and one level for high risk of bias (very low‐certainty evidence).
Pain scores (intraoperative and postoperative)
None of the included studies reported on pain at one day postoperatively
Quality of life measures
None of the included studies reported on quality of life.
Adverse events
No two trials provided data on the same outcomes for inclusion in a meta‐analysis and none specified when adverse events occurred. Al‐Fayez 2008 and Gui 2008 did not specify which adverse events they collected; however, Gui 2008 reported no unusual complications or adverse events, while Al‐Fayez 2008 reported a higher complication rate in eyes in the LASEK group compared with LASIK group. We downgraded the evidence one level for indirectness as the trial participants might not be representative of the review population and one level for high risk of bias (very low‐certainty evidence).
He 2006 reported that there were no severe complications that affected the participant's visual acuity; authors did report that none of the eyes in the LASEK group compared with 5 out of 39 eyes in the LASIK group experienced corneal flap striae. Likewise, none of the eyes in the LASEK group compared with 5 out of 39 eyes in the LASIK group had refractive over‐correction. Eight out of 37 eyes in the LASEK group compared with none in the LASIK group had refractive regression. Because adverse events only occurred in one group and not the other, we could not estimate the relative effects.
One trial reported excluding 3 out of 32 eyes in the LASEK group due to flap complications during epithelial flap preparation, resulting in damage to the epithelium (Kaya 2004).
None of the included studies reported keratectasias or dry eye. We downgraded the evidence of adverse events two levels for indirectness of evidence and one level for high risk of bias.
Discussion
Summary of main results
In this review of findings from four RCTs, involving 538 eyes of 392 participants with myopia of severity of up to 10.75 D, we did not find any high‐certainty evidence to precisely estimate differences in efficacy or adverse effects between LASEK and LASIK, if indeed they exist. The primary source of visual acuity outcomes was He 2006. Proportions of eyes that achieved UCVA of 20/40 or better and of 20/20 or better were similar over 12 months. One trial reported the proportion of eyes that achieved refractive correction within 0.5 D of the target (He 2006). In this study, the LASEK group was less likely to achieve the desired target refraction compared with the LASIK group. With regards to safety and adverse effects, one trial noted that 10% of eyes in the LASEK group (but none of in the LASIK group) had barely detectable or trace postoperative corneal haze, but authors did not specify the time of assessment (Kaya 2004). None of the included studies reported mean spherical equivalent of the refractive error at 1 year follow, pain at one day after surgery or quality of life scores. Overall, from the limited data available from the studies relevant to our review, LASEK and LASIK for refractive correction of myopia appear to be similar with regards to efficacy, accuracy, and safety.
Overall completeness and applicability of evidence
One trial consisted only of a published abstract, and the authors did not provide data for any of the review outcomes. Additionally, although none of the trials explicitly reported missing outcome data, we assume that loss to follow‐up explains why there were fewer eyes contributing data at trial completion than at randomization (He 2006). All the trials compared LASEK with LASIK in participants with myopia up to 10.75 D. We do not know whether these results apply to more severe myopia. At least three of the four trials were conducted outside the USA (in China and Turkey), so their applicability to myopic patients in the USA is unknown.
Certainty of the evidence
Overall, the certainty of evidence was very low, with most trials at unclear risk of bias; there was high risk of attrition bias in He 2006. The loss to follow‐up rate in He 2006 was higher in the LASEK group than the LASIK group. We downgraded the certainty of the evidence due to indirectness study populations and outcome measures and wide confidence intervals.
Potential biases in the review process
We followed standard Cochrane procedures to minimize bias in the review process. We are aware of no aspect of our procedures and analysis that had the potential to induce bias in our findings or conclusions.
Agreements and disagreements with other studies or reviews
In this review, we found similar effectiveness for LASEK versus LASIK for the treatment of mild to moderate myopia and myopic astigmatism with regards to UCVA outcomes and adverse effects. These findings are consistent with those of a prior review (Zhao 2014), which reviewed the results of 12 total studies (1 RCT and 11 non‐randomized comparative studies) comparing LASEK and LASIK for the treatment of any degree of myopia in people aged 18 years or older. In that review, there were no significant differences in visual and refractive outcomes for low to moderate myopia. Additionally, the review found that corneal haze was more severe in the LASEK group for moderate to high myopia compared to the LASIK group.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1 LASEK versus LASIK, Outcome 1 Eyes with UCVA of 20/20 or better at 1 month.
Comparison 1 LASEK versus LASIK, Outcome 2 Eyes with UCVA of 20/20 or better at 3 months.
Comparison 1 LASEK versus LASIK, Outcome 3 Eyes with UCVA of 20/20 or better at 6 months.
Comparison 1 LASEK versus LASIK, Outcome 4 Eyes with UCVA of 20/20 or better at 12 months.
Comparison 1 LASEK versus LASIK, Outcome 5 Eyes with UCVA of 20/40 or better at 1 month.
Comparison 1 LASEK versus LASIK, Outcome 6 Eyes with UCVA of 20/40 or better at 3 months.
Comparison 1 LASEK versus LASIK, Outcome 7 Eyes with UCVA of 20/40 or better at 6 months.
Comparison 1 LASEK versus LASIK, Outcome 8 Eyes with UCVA of 20/40 or better at 12 months.
Comparison 1 LASEK versus LASIK, Outcome 9 Eyes within ± 0.5 D of target refraction at 12 months.
Comparison 1 LASEK versus LASIK, Outcome 10 Sperical equivalent of the refractive error at 6 months.
Comparison 1 LASEK versus LASIK, Outcome 11 Postoperative corneal haze at 6 months.
Comparison 1 LASEK versus LASIK, Outcome 12 Postoperative corneal haze at 12 months.
| Laser‐assisted subepithelial keratectomy (LASEK) compared with laser‐assisted in‐situ keratomileusis (LASIK) for correcting myopia | ||||||
| Population: participants aged 18‐60 years with myopia ranging in severity up to 12 diopters (D) Settings: eye clinics Intervention: LASEK Comparison: LASIK | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of eyes | Certainty of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| LASIK | LASEK | |||||
| Uncorrected visual acuity (UCVA) of 20/20 or better follow‐up: 1 year | 931 per 1000* | 894 per 1000 | RR 0.96 (0.82 to 1.13) | 57 | ⊕⊝⊝⊝ | — |
| Uncorrected visual acuity (UCVA) of 20/40 or better follow‐up: 1 year | 793 per 1,000 | 714 per 1,000 (531 to 960) | RR 0.90 (0.67 to 1.21) | 57 (1 study) | ⊕⊝⊝⊝ | — |
| Proportion of participants who lost two or more lines of best‐corrected visual acuity (BCVA) follow‐up: 1 year | Not reported | — | ||||
| Eyes within ± 0.5 D of target refraction follow‐up: 1 year | 828 per 1000 | 571 per 1,000 | RR 0.69 (0.48 to 0.99) | 57 | ⊕⊝⊝⊝ | — |
| Postoperative corneal haze follow‐up: 1 year | 77 per 1000 | 162 per 1,000 | RR 2.11 (0.57 to 7.82) | 76 | ⊕⊝⊝⊝ | — |
| Postoperative pain score: 1 year | Not reported | — | ||||
| Adverse events (flap‐complications) | — | — | — | — | ⊕⊕⊝⊝ | Study investigators of Gui 2008 reported no unusual complications or adverse events, while study investigators of Al‐Fayez 2008 reported a lower complication rate in eyes in the LASIK group compared with LASEK group. Al‐Fayez 2008 and Gui 2008 did not specify which adverse events they collected. Study investigators of He 2006 reported that there were no severe complications that affected the participants' visual acuity. They did report 5 of 39 eyes in the LASIK group compared with none of the eyes in the LASEK group experienced corneal flap striae. Likewise, 5 of 39 eyes in the LASIK group compared with none of the eyes in the LASEK group had refractive over‐correction. None of the participants in the LASIK group compared with 8 of 37 eyes in the LASEK group had refractive regression. Since adverse events only occurred in one group and not the other, we could not estimate the relative effects. One trial reported excluding 3 of 32 eyes in the LASEK group due to flap complications during epithelial flap preparation, resulting in damage to the epithelium (Kaya 2004). |
| *The basis for the assumed risk is the comparison group risk. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). The assumed risk was calculated using the following formula: (number of events/number of eyes in the LASIK group) × 1000. | ||||||
| GRADE Working Group grades of evidence | ||||||
| aDowngraded for imprecision (wide confidence interval). | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Eyes with UCVA of 20/20 or better at 1 month Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 2 Eyes with UCVA of 20/20 or better at 3 months Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 3 Eyes with UCVA of 20/20 or better at 6 months Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 4 Eyes with UCVA of 20/20 or better at 12 months Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 5 Eyes with UCVA of 20/40 or better at 1 month Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 6 Eyes with UCVA of 20/40 or better at 3 months Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 7 Eyes with UCVA of 20/40 or better at 6 months Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 8 Eyes with UCVA of 20/40 or better at 12 months Show forest plot | 1 | 57 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.90 [0.67, 1.21] |
| 9 Eyes within ± 0.5 D of target refraction at 12 months Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 10 Sperical equivalent of the refractive error at 6 months Show forest plot | 2 | 144 | Mean Difference (IV, Fixed, 95% CI) | 0.07 [‐0.01, 0.15] |
| 11 Postoperative corneal haze at 6 months Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 12 Postoperative corneal haze at 12 months Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
