Cirugía de derivación trabecular ab interno con Trabectome para el glaucoma de ángulo abierto
Resumen
Antecedentes
El glaucoma es la principal causa de ceguera irreversible. Las técnicas quirúrgicas mínimamente invasivas, como la cirugía de derivación trabecular ab interno, se han introducido para detener la evolución del glaucoma.
Objetivos
A la luz de los posibles efectos beneficiosos para las personas con glaucoma de ángulo abierto y de la amplia aceptación de la técnica, es importante evaluar de forma crítica la evidencia sobre si el tratamiento con cirugía de derivación trabecular ab interno con Trabectome es eficaz y seguro.
Métodos de búsqueda
Se hicieron búsquedas en el Registro Cochrane central de ensayos controlados (Cochrane Central Register of Controlled Trials, CENTRAL; que contiene el Registro de ensayos del Grupo Cochrane de Salud ocular y de la visión [Cochrane Eyes and Vision]; 2020, número 7); Ovid MEDLINE; Ovid Embase; el registro ISRCTN; ClinicalTrials.gov; y la ICTRP de la OMS. La fecha de la búsqueda fue el 17 de julio de 2020.
Criterios de selección
Se buscaron ensayos controlados aleatorizados (ECA) de cirugía de derivación trabecular ab interno con Trabectome comparada con otros tratamientos quirúrgicos (otras técnicas con dispositivos mínimamente invasivos para el glaucoma, trabeculectomía), tratamiento con láser o tratamiento médico. También se incluyeron los ensayos en los que estos dispositivos se combinaron con la facoemulsificación en comparación con la facoemulsificación combinada con otra cirugía del glaucoma o sola.
Obtención y análisis de los datos
Se utilizaron los procedimientos metodológicos estándar previstos por Cochrane. El desenlace principal fue la proporción de participantes sin medicación (que no usaban colirios). Los desenlaces secundarios incluyeron el cambio medio en la presión intraocular (PIO), la proporción de participantes que requirieron una cirugía adicional de glaucoma, el cambio medio en la calidad de vida, la proporción de participantes que alcanzaron una PIO de 21 mmHg o menos, 17 mmHg o menos, o 14 mmHg o menos y la tasa de progresión del campo visual. Los efectos adversos fueron la proporción de participantes que presentaron complicaciones intra y posoperatorias. Todos los desenlaces se midieron a corto (seis a 18 meses), medio (18 a 36 meses) y largo plazo (a partir de 36 meses).
Resultados principales
En esta actualización se incluye un ECA que había sido identificado previamente como un estudio en curso en la publicación de 2016. Este ensayo fue un ECA de un centro único con un solo cirujano realizado en Canadá con 19 participantes. Los participantes eran adultos con glaucoma de ángulo abierto, ángulos abiertos y tenían una PIO inadecuadamente controlada que requería una intervención quirúrgica. El estudio se finalizó antes de que se alcanzara el tamaño muestral previsto "debido a la lentitud del reclutamiento y a la creciente indeterminación clínica conforme pasa el tiempo". Esto redujo la potencia estadística del estudio para detectar efectos clínicamente importantes. El ensayo se consideró con alto riesgo de sesgo de desgaste, notificación y otras posibles fuentes de sesgos. Los riesgos de sesgo de realización y de detección son poco claros.
El grupo de intervención de diez personas se sometió a una trabeculotomía ab interna combinada con la extracción de cataratas (faco‐AIT) y el grupo de comparación de nueve personas se sometió a una trabeculectomía con mitomicina C combinada con la extracción de cataratas (faco‐Trab), una de las cuales se perdió durante el seguimiento. Siete de diez participantes del grupo de faco‐AIT y cuatro de ocho del grupo de faco‐Trab no recibían mediación (no usaban colirios) a los 12 meses (odds ratio [OR] 2,33; intervalo de confianza [IC] del 95%: 0,34 a 16,2; evidencia de certeza muy baja). A los 12 meses, el cambio medio en la PIO fue peor para el faco‐AIT que para el faco‐Trab, pero esta evidencia fue muy incierta (diferencia de medias [DM] 3,70 mmHg; IC del 95%: ‐1,44 a 8,84; evidencia de certeza muy baja) en el grupo de faco‐AIT, al igual que la diferencia en el número medio de colirio reductor de la PIO administrado al día (DM ‐0,41; IC del 95%: ‐1,22 a 0,40; evidencia de certeza muy baja).
Sólo uno de los participantes del grupo de faco‐AIT necesitó una nueva cirugía para el glaucoma. El protocolo del estudio afirmó que se midió la calidad de vida y la progresión del campo visual, pero no se informó acerca de estos.
Los ocho participantes con datos completos del grupo de faco‐Trab y ocho de diez del grupo de faco‐AIT tuvieron al menos una complicación posoperatoria temprana o tardía (p.ej., pico de PIO en el día 1, hipotonía, derrame coroideo, fuga o encapsulamiento de la ampolla, uveítis o sinequias anteriores periféricas).
La certeza de la evidencia fue muy baja, debido principalmente al alto riesgo de sesgo de varios dominios en este estudio y a la gran imprecisión de todas las estimaciones.
También se identificó un estudio en curso, localizado en la Plataforma de registros internacionales de ensayos clínicos (ICTRP): un ECA multicéntrico, abierto, que compara Trabectome con la trabeculectomía ab interno con microgancho. Los investigadores del estudio tienen previsto reclutar a 120 adultos de entre 20 y 90 años de edad. El desenlace principal es la duración del éxito de tratamiento. Los desenlaces secundarios incluyen la PIO posoperatoria, el número de fármacos antiglaucoma y los eventos adversos.
Conclusiones de los autores
En la actualidad no existe evidencia de calidad alta de los desenlaces de la cirugía de derivación trabecular ab interno con Trabectome para el glaucoma de ángulo abierto. Se necesitan ECA bien diseñados para evaluar la eficacia y la seguridad a largo plazo de esta técnica.
PICO
Resumen en términos sencillos
¿Cuáles son los riesgos y beneficios de la cirugía mínimamente invasiva (Trabectome) para tratar el glaucoma (enfermedad ocular común)?
¿Por qué es importante esta pregunta?
El glaucoma es un trastorno ocular habitual que afecta al nervio óptico. Puede darse en personas de todas las edades, pero es más frecuente en adultos mayores de 70 años.
Existen diferentes tipos de glaucoma. El más habitual es el “glaucoma primario de ángulo abierto”. Tiende a desarrollarse lentamente durante muchos años. Está causado por una presión anormalmente alta en el ojo que se produce cuando el sistema de drenaje ocular no funciona correctamente y se acumula líquido en el ojo. Este aumento de la presión daña el nervio óptico y puede causar ceguera parcial o incluso total.
Existen varios tratamientos distintos para el glaucoma. Entre ellos se encuentran las gotas para los ojos (colirios), el tratamiento con láser y la cirugía. La cirugía suele utilizarse solo si el tratamiento con colirios o con láser no ha funcionado.
La cirugía estándar suele consistir en extirpar parte de los tubos de drenaje del ojo para permitir que el líquido drene más fácilmente. Puede realizarse con anestesia local (con el paciente despierto) o con anestesia general (con el paciente dormido). La cirugía estándar suele acarrear complicaciones (como hemorragias oculares durante y después de la operación), y las personas pueden necesitar que se repita la operación.
Una posible alternativa a los procedimientos quirúrgicos estándares es la cirugía con Trabectome. La cirugía con Trabectome se realiza con anestesia local y consiste en utilizar un instrumento especialmente diseñado (Trabectome) para extirpar una porción de tejido con el fin de mejorar la vía de drenaje del ojo. Los cirujanos hacen una incisión más pequeña en el ojo que en la cirugía estándar, y esto podría suponer menos riesgos para el paciente.
Para averiguar los riesgos y beneficios de la cirugía con Trabectome se examinó la evidencia de los estudios de investigación.
¿Cómo se identificó y evaluó la evidencia?
Se buscaron en la literatura médica los estudios controlados aleatorizados (estudios clínicos en los que las personas se asignaran al azar a uno de dos o más grupos de tratamiento), ya que proporcionan la evidencia más sólida sobre los efectos de un tratamiento. Luego se compararon los resultados y se resumió la evidencia de todos los estudios. Finalmente, la confianza en la evidencia se calificó según factores como las metodologías y los tamaños de los estudios, así como la consistencia de los hallazgos entre los estudios.
¿Qué se encontró?
Se encontró un estudio con un total de 19 personas con glaucoma. El estudio se realizó en Canadá y fue financiado por la Universidad de Alberta. A los participantes se realizó un seguimiento de hasta un año después de la cirugía. Todos los participantes fueron operados por el mismo cirujano. La cirugía con Trabectome se comparó con una intervención quirúrgica estándar (trabeculectomía).
Según el único estudio encontrado, no es posible determinar si la cirugía con Trabectome es mejor o peor que la cirugía convencional. El estudio fue muy pequeño y hubo problemas con la forma en que se realizó. Por lo tanto, se tiene muy poca confianza en los resultados acerca de los siguientes:
‐ necesidad de utilizar colirios, o utilizar menos, al año después de la cirugía;
‐ mejora de la presión ocular al año de la cirugía;
‐ necesidad de más cirugía; y
‐ complicaciones.
No se estudiaron otros aspectos, como las alteraciones en la visión o la calidad de vida.
Se identificó un estudio en curso que se está realizando en Japón. Una vez que se disponga de los resultados de este estudio, será posible añadirlos a futuras versiones de esta revisión.
¿Qué significa esto?
Se desconoce si la cirugía con Trabectome es mejor o peor que otros tratamientos para el glaucoma. Esto se debe a que existe muy poca evidencia en este momento. En el futuro sería útil que se realizaran más estudios en esta área. En concreto, se necesitan estudios sólidos que evalúen los riesgos y beneficios a largo plazo de la cirugía con Trabectome.
¿Cuál es el grado de actualización de esta revisión?
La evidencia de esta revisión Cochrane está actualizada hasta julio de 2020.
Authors' conclusions
Summary of findings
| Phaco‐AIT compared with Phaco‐Trab for open‐angle glaucoma | ||||||
| Patient or population: participants 40 to 85 years of age with open‐angle glaucoma Settings: eye service Intervention: phaco‐AIT: combined Trabectome and cataract extraction with intraocular lens insertion Comparison: phaco‐Trab: combined trabeculectomy with mitomycin C and cataract extraction with intraocular lens insertion | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Assumed risk (phaco‐Trab) | Corresponding risk (phaco‐AIT) | |||||
| Proportion of participants who were medication‐free (not using drops) at 12 months | 500 per 1000 | 700 per 1000 | OR 2.33 | 18 (1 RCT) | ⊕⊝⊝⊝ | |
| Mean change in IOP (mmHg) at 12 months | The mean change in IOP in the phaco‐Trab group was ‐6.4 (SD 8.7) mmHg | MD: 3.70 (95% CI ‐1.44 to 8.84) | 18 (1 RCT) | ⊕⊝⊝⊝ | ||
| Mean change in number of IOP‐lowering drops taken per day at 12 months | The mean change in the number of IOP‐lowering medications in the phaco‐Trab group was ‐0.51 SD 0.81) | MD: ‐0.41 (95% CI ‐1.22 to 0.40) | 18 (1 RCT) | ⊕⊝⊝⊝ | ||
| Proportion of participants who required further glaucoma surgery at 12 months | 1 participant required further glaucoma surgery in the phaco‐AIT group vs. none in the phaco‐Trab group (approximate OR 3.00, 95% CI 0.11 to 83.36) | 18 (1 RCT) | ⊕⊝⊝⊝ | |||
| Rate of visual field progression | The study protocol declared that this outcome was measured, but it was not reported | |||||
| Mean change in health‐related quality of life | The study protocol declared that this outcome was measured, but it was not reported | |||||
| Proportion of participants experiencing intra‐ and postoperative complications | Overall, 8 of 10 participants (80%) experienced any complication in the phaco‐AIT groups vs. 8 of 8 (100%) in the phaco‐Trab group. Data are sparse and effect estimates are extremely imprecise. Early and late postoperative complications are presented in the Effects of interventions. | ⊕⊝⊝⊝ | ||||
| *The assumed risk is the median risk in control groups in the included studies (rounded to nearest 10 per 1000). The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; IOP: intraocular pressure; MD: mean difference; OR: odds ratio; RCT: randomised controlled trial | ||||||
| GRADE Working Group grades of evidence High‐certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate‐certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low‐certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low‐certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | ||||||
| 1) downgraded ‐1 level for serious limitations in study design 2) downgraded ‐2 level for imprecision | ||||||
Background
Description of the condition
Glaucoma is a chronic progressive optic neuropathy affecting up to 4% of people by 80 years of age (Burr 2007). It is the leading cause of irreversible blindness, affecting 60 million people globally (Quigley 2006). This figure is expected to increase to 80 million people by 2020. Open‐angle glaucoma (OAG) is the most common type, accounting for three‐quarters of cases (Quigley 2006). In one large population cohort, one in six people with OAG became bilaterally blind (Peters 2013). The only proven way to prevent vision loss is to reduce the pressure inside the eye (intraocular pressure (IOP)) over the long term (AGIS 2000; CNTG Study Group 1998; Heijl 2002; Kass 2002). Approaches to reducing IOP include medical therapy, laser treatments, and surgery. As commercially available eye drop preparations have a short‐lasting effect, medical therapy requires eye drops to be instilled one or more times daily for life. Adherence is very poor, even if use is monitored (Friedman 2009; Okeke 2009). Conventional surgical techniques such as trabeculectomy are associated with significant risks, with more than 40% of patients developing perioperative complications (Kirwan 2013; Lichter 2001), and 7% to 18% of cases requiring re‐operation (Gedde 2012; Kirwan 2013). These techniques are therefore often reserved for disease that is progressing despite other treatments (King 2013).
Description of the intervention
A number of minimally invasive surgical techniques have recently been developed with the aim of achieving long‐term reduction of IOP with a better safety profile than conventional surgery (Francis 2011). Among them, ab interno trabecular bypass surgery (also known as trabeculotomy ab interno and trabeculectomy ab interno) with the Trabectome (NeoMedix, Tustin, CA, USA) is a Food and Drug Administration (FDA)‐approved and CE marked treatment.
How the intervention might work
The trabecular meshwork is the eye's main site of resistance to outflow of aqueous humour (Overby 2009). The Trabectome is designed to selectively ablate a portion of the trabecular meshwork, enabling aqueous humour to have direct access to the canal of Schlemm and thence the collector channels (Francis 2006). This is intended to promote aqueous outflow, thereby reducing IOP. Tissue ablation is performed electrosurgically using a 19.5‐gauge instrument, which is introduced into the eye via a 1.6‐mm incision in the cornea.
Why it is important to do this review
Consultation with patients and healthcare professionals has identified a need for better treatments for glaucoma (James Lind Alliance 2013). Minimally invasive glaucoma procedures may safely and effectively reduce IOP in the long term, removing concerns about permanent vision loss due to nonadherence to eye drops. A single treatment may also be more acceptable to patients than daily and indefinite self‐administration of eye drops. Initial results of ab interno trabecular bypass surgery with the Trabectome were reported in 2005 (Minckler 2005). Post‐market surveillance data show that more than 4600 treatments were performed between 2004 and 2013 at over 200 centres worldwide (Mosaed 2014; NeoMedix, on file). In light of the potential benefits for patients and the widespread uptake of the technique, it is important to critically evaluate the evidence for whether treatment with the Trabectome is both efficacious and safe. Importantly, Trabectome surgery may be combined with phacoemulsification (cataract surgery), a sight‐restoring operation to remove the natural lens of the eye when it has lost clarity. Since phacoemulsification itself reduces IOP (Mansberger 2012), we planned specifically to examine the evidence for efficacy of Trabectome treatment in people who have concomitant phacoemulsification compared to those who do not.
This Cochrane Review is part of a suite of reviews on minimally invasive glaucoma surgery (MIGS) techniques and devices currently being undertaken by the Cochrane Eyes and Vision MIGS Consortium, which includes Hydrus Schlemm's canal Microstent (Ivantis Inc., Irvine, CA, USA) (Otarola 2017), endoscopic cytophotocoagulation (Endo Optiks, Waltham, MA, USA) (Tóth 2017), XEN Glaucoma Implant (AqueSys Implant, Aliso Viejo, CA, USA) (King 2018), iStent and iStent inject (Glaukos Corporation, Laguna Hills, CA, USA) (Le 2019), and supraciliary microstent surgery (Sandhu 2017).
Objectives
In light of the potential benefits for people with open‐angle glaucoma and the widespread uptake of the technique, it is important to critically evaluate the evidence for whether treatment with ab interno trabecular bypass surgery with Trabectome is both efficacious and safe.
Methods
Criteria for considering studies for this review
Types of studies
We included randomised controlled trials (RCTs) only. We included all study reports published in English (or which have been translated into English), irrespective of their publication status. We planned to exclude within‐person studies because of the potential for medical treatments, such as topical beta blockers, used for one eye to influence the outcome in the other eye (Piltz 2000).
Types of participants
Participants could have OAG of any type, including primary and secondary OAG. We excluded closed‐angle glaucoma. As there are no universally accepted criteria by which glaucoma may be defined, we permitted studies to use their own definitions of glaucoma (provided these were clearly stated). We also included participants with ocular hypertension, normal‐tension glaucoma, or possible glaucoma (suspects for glaucoma). We applied no restrictions regarding location, setting, or demographic factors.
Types of interventions
The intervention was ab interno trabeculotomy performed with the Trabectome (NeoMedix, Tustin, CA, USA). Although it is possible to ablate a variable amount of the trabecular meshwork (typically an arc of 40°) and to vary the electrosurgical power employed (Francis 2006), we did not apply any particular inclusion or exclusion criteria to these or other treatment delivery parameters.
We compared ab interno trabeculotomy performed with the Trabectome to the following:
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laser treatment (selective laser trabeculoplasty or argon laser trabeculoplasty);
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other MIGS techniques;
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conventional glaucoma surgery (trabeculectomy);
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medical therapy.
We also included trials in which these devices were combined with phacoemulsification compared to phacoemulsification in combination with other glaucoma surgery or alone.
Types of outcome measures
We did not use the reporting of particular outcomes as a criterion for eligibility for this review. We did not exclude studies from this review solely on the grounds of an outcome of interest not being reported.
We reported outcomes in the short term (6 to 18 months), medium term (18 to 36 months), and long term (36 months or longer).
Primary outcomes
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Proportion of participants who were medication‐free (not using eye drops).
Several different glaucoma outcome measures have been specified as primary outcomes in other Cochrane Reviews and Protocols (Ismail 2015). A recent study classified IOP, visual field, safety, and anatomic outcomes as being highly important to glaucoma experts (Ismail 2016). A panel of patients from the Patient and Public Involvement Group of the National Institute for Health Research (NIHR) Biomedical Research Centre for Ophthalmology identified drop‐free disease control as a highly valued outcome (unpublished). We chose a patient‐centred primary outcome. In assessing this effect measure, we planned to report how prescribing IOP‐lowering eye drops was determined during follow‐up. We planned to examine whether the people measuring IOP and those deciding on prescribing IOP‐lowering eye drops were masked to the treatment group.
Secondary outcomes
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Mean change in IOP measured using Goldmann applanation tonometry.
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Mean change in number of IOP‐lowering drops taken per day.
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Proportion of participants who achieve an IOP of 21 mmHg or less.
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Proportion of participants who achieve an IOP of 17 mmHg or less.
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Proportion of participants who achieve an IOP of 14 mmHg or less.
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Proportion of participants who required further glaucoma surgery, including laser, as recorded by the investigators of the included trial.
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Rate of visual field progression (decibels (dB)/time) or proportion of participants whose field loss progressed in the follow‐up period.
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Mean change in HRQoL.
Adverse effects
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Proportion of participants experiencing intra‐ and postoperative complications, including, but not restricted to, the following:
-
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loss of visual acuity (more than 2 Snellen lines or more than 0.3 logMAR, according to the method of recording visual acuity; or loss of light perception);
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bleeding, as recorded by the investigators;
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endophthalmitis, as recorded by the investigators;
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IOP spikes (postoperative rise in IOP, measured using Goldmann applanation tonometry, of more than 10 mmHg compared to the previous assessment, including measurements taken during the first postoperative month).
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Search methods for identification of studies
Electronic searches
The Cochrane Eyes and Vision Information Specialist conducted systematic searches in the following databases for randomised controlled trials and controlled clinical trials. There were no restrictions to language or year of publication. The date of the search was 17 July 2020.
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Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 7) (which contains the Cochrane Eyes and Vision Trials Register) in the Cochrane Library (searched 17 July 2020) (Appendix 1).
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MEDLINE Ovid (1946 to 17 July 2020) (Appendix 2).
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Embase Ovid (1980 to 17 July 2020) (Appendix 3).
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ISRCTN registry (www.isrctn.com/editAdvancedSearch; searched 17 July 2020) (Appendix 4).
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US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov; searched 17 July 2020) (Appendix 5).
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World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp; searched 17 July 2020) (Appendix 6).
Searching other resources
We searched the reference lists of the included study for other possible studies, and we planned to contact any individuals or organisations we believed may have conducted or be conducting relevant RCTs. We also searched the website of the manufacturer (NeoMedix Inc., Tustin, CA, USA; www.trabectome.com) for any information on forthcoming trials.
Data collection and analysis
Selection of studies
For the 2021 update, two review authors (AS, KH) independently screened titles and abstracts of all articles identified by the search. If abstracts were not available, we planned to screen full‐text articles. Two review authors (AS, KH) independently assessed full‐text reports of all potentially eligible studies. In case of disagreement regarding eligibility, a third review author would arbitrate. If we rejected any full‐text reports, we planned to record the reasons for this.
Data extraction and management
Two review authors (AS, KH) independently extracted study characteristics from reports of each study and entered the data into Review Manager 5 (RevMan 5) (Review Manager 2014). Two authors (KH, GV) independently extracted the data for the analyses.
Data collected in Appendix 7 was presented in the 'Characteristics of included studies' table.
If data on included studies were missing or unclear, we planned to contact the individuals or organisations involved to obtain clarification. We intended to collect and use the most detailed numerical data available to facilitate analyses of included studies. We planned to obtain these data from individuals or organisations instead of using less precise methods, such as extracting numeric data from graphs. If this was necessary, two review authors would independently extract the data, and a third review author would arbitrate in case of disagreement.
Assessment of risk of bias in included studies
We used the original Cochrane 'Risk of bias' tool (RoB 1) as described in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions to assess the risk of bias and assign judgements of this for included studies (Higgins 2017).
Measures of treatment effect
We reported outcomes in the short term (6 to 18 months), medium term (18 to 36 months), and long term (36 months or longer) after randomisation.
The primary outcome was the proportion of participants who were medication‐free. We used the odds ratio (OR) as the treatment effect measure.
We reported mean change in IOP and mean change in number of IOP‐lowering drops taken per day. We reported the proportion of participants achieving various target IOPs or requiring further glaucoma surgery using ORs as the treatment effect measure. We planned to report HRQoL outcomes as differences in means or ORs for continuous and binary data, respectively. We reported secondary safety outcomes as ORs.
Unit of analysis issues
We noted whether the studies included one or two eyes from each participant and whether randomisation had been conducted at the level of the participant or the eye. There is a potential for medical treatments, such as topical beta blockers, used for one eye to influence the outcome in the other eye (Piltz 2000). We therefore planned to exclude studies that adopted a paired design. Surgery to lower IOP in one eye may also affect the IOP of the other eye (Radcliffe 2010).
Dealing with missing data
We planned to minimise missing outcome data by contacting individuals and organisations to try to obtain them. If the data were unavailable, but the level of missing data in each group and reasons for missing data in each group were similar, we may simply analyse available case data if an intention‐to‐treat (ITT) analysis had not been performed. If the authors had conducted their own ITT analysis despite missing data, we planned to document whether they provided any justification for the method they had used to deal with missing data and whether they had compared their ITT result with an available case result.
Assessment of heterogeneity
We planned to assess heterogeneity between trials by careful examination of the study reports, assessing forest plots, and an examination of the I2 value with its 95% confidence interval. We would consider I2 values greater than 50% as indicating substantial heterogeneity and, therefore, suggesting that meta‐analysis might not be wise, however, we would give consideration to the consistency of the effect estimates. If all estimates were in the same direction, we might meta‐analyse, even where heterogeneity was evident, and comment on the heterogeneity.
Assessment of reporting biases
We planned to use a funnel plot to assess the risk of publication bias if we included more than 10 trials in the review.
Data synthesis
We planned to undertake a meta‐analysis where data appeared clinically, methodologically, and statistically homogeneous. We would check that participants, interventions, comparators, and outcomes were sufficiently similar to give a clinically meaningful result and that our I2 value result indicated little inconsistency (that is I2 < 50%). If all estimates were in the same direction, we might meta‐analyse even where heterogeneity was evident but would comment on this. We planned to use a random‐effects model unless there were fewer than three eligible studies, in which case we would use a fixed‐effect model.
Subgroup analysis and investigation of heterogeneity
In future updates of this review, we do not plan to conduct subgroup analysis.
Sensitivity analysis
We planned to assess the impact of including studies at high risk of bias.
Summary of findings and assessment of the certainty of the evidence
We prepared a table to summarise the findings of the review, including the assessment of the quality of evidence for all outcomes using the GRADE approach (Langendam 2013).
We reported on the following outcomes at short‐term follow‐up (6 to 18 months) in 'summary of findings Table 1' for each comparison listed in the Types of interventions:
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proportion of participants who were medication‐free (not using eye drops);
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mean change in IOP, measured using Goldmann applanation tonometry;
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mean change in number of IOP‐lowering drops taken per day;
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proportion of participants who required further glaucoma surgery, including laser;
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rate of visual field progression (dB/time) or proportion of participants whose field loss progressed in the follow‐up period;
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mean change in HRQoL;
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proportion of participants experiencing intra‐ and postoperative complications (any time point).
Results
Description of studies
Results of the search
The electronic searches run in 2016 yielded a total of 155 references. The Cochrane Information Specialist removed 41 duplicate records, and two review authors (GG and KH) independently screened the remaining 114 reports for potentially eligible studies, namely possible RCTs.
Update searches run in July 2020 yielded a further 268 records (Figure 1). The Cochrane Information Specialist removed 107 duplicates, and we screened the remaining 161 references. We obtained three full‐text reports for further assessment. We included one new study (Ting 2018) and excluded one ongoing study (NCT03894631). We have identified a new ongoing study (JPRN‐UMIN000030167) and will assess this for inclusion when data become available.
Study flow diagram.
We are not aware of any other individuals or organisations who have conducted or may be conducting relevant RCTs. A search of the website of the manufacturer (NeoMedix Inc., Tustin, CA, USA; www.trabectome.com) did not yield any information on forthcoming trials.
Included studies
The 2021 update included one published trial that met our inclusion criteria (Ting 2018), which was an ongoing study in the previous published version of this review (Hu 2016).
Design: prospective RCT
Sample sizes: 19 (10 phaco‐Trabectome, 9 phaco‐trabeculectomy); the original protocol described a planned sample size of 52 (26 per study arm), however, the trial report describes a planned sample size of 26 (13 per group)
Setting: eye service
Participants: people with open‐angle glaucoma
Interventions: phaco‐Trabectome (phaco‐ab interno trabeculectomy, phaco‐AIT) versus phaco‐trabeculectomy (phaco‐Trab) with mitomycin C
Outcomes: primary outcomes were mean IOP at 6 months and surgical complications; secondary outcomes were mean IOP at 12 months, achievement of target IOP, number of glaucoma medications, and rate of secondary surgery
Excluded studies
We excluded one ongoing study (NCT03894631), as both the intervention and comparator were in the same participant, and per our protocol (Hu 2015), we excluded these studies from the outset.
Ongoing studies
In the 2021 update, we identified one ongoing study that met our inclusion criteria (JPRN‐UMIN000030167). The study started in April 2018 and is being conducted in Japan. It is a multicentre RCT with no masking of participants, personnel, or outcome assessors. It compares Trabectome to ab interno trabeculectomy using microhook. Participants will be between 20 and 90 years of age, male and female, and sample size is set at 120 people. The study includes participants with ocular hypertension and open‐angle glaucoma with IOPs of 20 to 39 mmHg while on treatment with at least one antiglaucoma medication. The primary outcome is duration of treatment success (defined as IOP 5 to 21 mmHg, a 20% reduction from baseline, and no additional glaucoma medical therapy or additional glaucoma surgery). Secondary outcomes include postoperative IOP, number of antiglaucoma medications, and adverse events. See Characteristics of ongoing studies for further information.
Risk of bias in included studies
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Allocation
Random sequence generation
Participants were block randomised to either phaco‐AIT or phaco‐Trab using a randomly permutated block scheme. We assessed the trial to have low risk of selection bias from this source.
Allocation concealment
Study enrolment and randomisation were performed by a study coordinator to ensure allocation concealment. We assessed the trial to have low risk of selection bias from this source.
Blinding
Performance bias
As the trial report did not mention masking of participants and personnel, we assessed the trial to have unclear risk of performance bias.
Detection bias
As the trial report did not mention masking of outcome assessors, we assessed the trial to have unclear risk of detection bias.
Incomplete outcome data
One of nine participants in the phaco‐Trab group was lost to follow‐up by 6 months and did not return at 12 months. One of the 10 participants in the phaco‐AIT group missed follow‐up at 6 months but returned to follow‐up at 12 months. We assessed the trial to have high risk of attrition bias.
Selective reporting
We planned to report quality of life measures and visual acuity according to the original protocol, but we did not include these in the trial report. We reported achievement of target, but we did not include this outcome measure in the protocol. We assessed the trial to be at high risk of reporting bias.
Other potential sources of bias
The original protocol described a planned sample size of 52 (26 per study arm). However, the trial report describes a planned sample size of 26 (13 per group). It is unclear why the planned sample size changed.
The study was terminated before the intended sample size was reached 'due to slow recruitment and increasing lack of clinical equipoise over time'. The authors state, 'it became more apparent during the study that there was limited overlap between patients suitable for AIT and conventional trabeculectomy'. This reduces the power of the study to detect statistically significant differences.
We note that modifications to ocular hypotensive medications were made at the discretion of the surgeon, not according to a prespecified protocol. This could introduce bias if the surgeon was not masked to the treatment group.
Overall, we assessed the trial to be at high risk of other potential sources of bias.
Effects of interventions
See: Summary of findings 1 Phaco‐AIT compared with Phaco‐Trab for open‐angle glaucoma
Phaco‐AIT versus phaco‐Trab
In Ting 2018, several outcomes of our review were not analysed, but we have been able to calculate the outcomes from the data presented in the article. See summary of findings Table 1. The study included 19 participants (10 phaco‐AIT and 9 phaco‐Trab). One participant was lost to follow‐up after three months.
Proportion of participants who were medication‐free (not using eye drops)
The following table presents the proportion of participants who were medication‐free at baseline and during follow‐up. At 12 months, we found no evidence of a difference between phaco‐AIT and phaco‐Trab at 12 months (Analysis 1.1), but estimates were very imprecise (OR: 2.33, 95% confidence interval (CI) 0.34 to 16.2; very low‐certainty of evidence, downgraded (‐1) for risk of bias and (‐2) for imprecision).
| phaco‐AIT | phaco‐Trab | |||
|---|---|---|---|---|
| Time point | n (%) | Total | n (%) | Total |
| baseline | 2 (20%) | 10 | 2 (22%) | 9 |
| 6 months | 6 (67%) | 9 | 6 (75%) | 8 |
| 12 months | 7 (70%) | 10 | 4 (50%) | 8 |
Mean change in IOP measured using Goldmann applanation tonometry
Both techniques reduced IOP compared to baseline (Analysis 1.2). At 12 months, the MD in the mean IOP change was 3.70 mmHg (95% CI ‐1.44 to 8.84), favouring phaco‐Trab, but this evidence was very uncertain (very low‐certainty of evidence, downgraded (‐1) for risk of bias and (‐2) for imprecision). In this analysis, the SD of the difference in IOP change was not available, and we computed it using SDs of baseline and final values, assuming a correlation of 0.7 between these measures.
Mean change in number of IOP‐lowering drops taken per day
At 12 months, there was no evidence of a difference in the mean change in IOP‐lowering drops at 12 months for phaco‐AIT versus phaco‐Trab (MD ‐0.41, 95% CI ‐1.22 to 0.40; Analysis 1.3; very low‐certainty of evidence, downgraded (‐1) for risk of bias and (‐2) for imprecision).
Proportion of participants who achieved an IOP of 21 mmHg, 17 mmHg, 14 mmHg, or less
The following table presents the proportion of participants achieving different targets of IOP at baseline and during follow‐up. At 12 months, the OR (95% CI) of the proportion of participants with IOP of 21, 17, 14 mmHg or less were 1.29 (0.07 to 24.38; Analysis 1.4), 0.90 (0.13 to 6.08; Analysis 1.5), and 0.19 (0.01 to 2.29; Analysis 1.6), meaning that no evidence of a difference was found, but estimates were very imprecise due to the limited sample size (very low‐certainty of evidence, downgraded (‐1) for risk of bias and (‐2) for imprecision). Moreover, one participant in the phaco‐AIT group received glaucoma surgery at 10 months.
| Intervention | ≤ 21 mmHg | ≤ 17 mmHg | ≤ 14 mmHg | Total | |
|---|---|---|---|---|---|
| baseline | phaco‐AIT | 6 (60%) | 5 (50%) | 0 | 10 |
| phaco‐Trab | 5 (56%) | 1 (11%) | 0 | 9 | |
| 6 months | phaco‐AIT | 7 (78%) | 5 (56%) | 2 (22%) | 9 |
| phaco‐Trab | 7 (88%) | 6 (75%) | 1 (13%) | 8 | |
| 12 months | phaco‐AIT | 9 (90%) | 6 (60%) | 1 (10%) | 10 |
| phaco‐Trab | 7 (88%) | 5 (63%) | 3 (38%) | 8 |
Proportion of participants who required further glaucoma surgery, including laser, as recorded by the investigators of the included trial
One of 10 participants (10%) in the Phaco‐AIT group required further glaucoma surgery (Ahmed valve at 10 months postoperative). None of the nine participants (0%) in the Phaco‐Trab group remaining under follow‐up required further glaucoma surgery. At 12 months, data were sparse and the evidence was very uncertain (OR 3.00, 95% CI 0.11 to 83.4; Analysis 1.7; very low‐certainty of evidence, downgraded (‐1) for risk of bias and (‐2) for imprecision).
Mean change in HRQoL
The study protocol declared that this outcome was measured, but it was not reported.
Rate of visual field progression (dB/time) or proportion of participants whose field loss progressed in the follow‐up period
The study protocol declared that this outcome was measured, but it was not reported.
Proportion of participants experiencing intra‐ and postoperative complications
Overall, 8 of 10 participants (80%) experienced any complication in the phaco‐AIT groups versus 8 of 8 (100%) in the phaco‐Trab group. Because of sparse data, estimates were very imprecise (OR 0.20, 95% CI 0.01 to 4.82; Analysis 1.8; very low‐certainty of evidence, downgraded (‐1) for risk of bias and (‐2) for imprecision).
We report the following details on early complications (within 30 days postoperative) and late complications (> 30 days postoperative), and more than one complication is possible for each participant based on available cases.
Early complications
Phaco‐AIT: 8 of 10 participants (80%): peripheral anterior synechiae (5), day 1 IOP spike (5), hyphema (4), steroid response (1) as mild or moderate early complications (more than one complication is possible for each participant).
Phaco‐Trab: 8 of 8 participants (100%): peripheral anterior synechiae (1), day 1 IOP spike (3), hypotony (3), bleb leak (2), which were mild or moderate complications; and hypotony maculopathy (2) and choroidal effusion (2) as severe early complications (more than one complication is possible for each participant).
There was no evidence of a difference in the proportion of participants with early complications for phaco‐AIT vs phaco‐Trab, but estimates were very imprecise (OR 0.50, 95% CI 0.04 to 6.68; Analysis 1.9; very low‐certainty of evidence, downgraded (‐1) for risk of bias and (‐2) for imprecision).
Late complications
Phaco‐AIT: 6 of 10 participants (60%): peripheral anterior synechiae (5), chronic‐recurrent uveitis (2) as mild or moderate early complications (more than one complication is possible for each participant).
Phaco‐Trab: 3 of 8 participants (38%): peripheral anterior synechiae (2), chronic‐recurrent uveitis (2), encapsulated bleb (1) as mild or moderate complications (more than one complication is possible for each participant).
There was no evidence of a difference in the proportion of participants with late complications for phaco‐AIT vs phaco‐Trab, but estimates were very imprecise (OR 2.50, 95% CI 0.37 to 16.9; Analysis 1.10; very low‐certainty of evidence, downgraded (‐1) for risk of bias and (‐2) for imprecision).
Discussion
We found one RCT reporting the outcomes of ab interno trabecular bypass surgery with Trabectome for open‐angle glaucoma (Ting 2018) and one RCT that is in progress (JPRN‐UMIN000030167).
Summary of main results
All efficacy and safety estimates obtained in this study were unreliable because of risk of bias and a very small sample size.
Overall completeness and applicability of evidence
We believe that our conclusions are supported by a thorough search of available evidence, as outlined in the published protocol (Hu 2015).
Quality of the evidence
The included study was terminated before the intended sample size was reached 'due to slow recruitment and increasing lack of clinical equipoise over time'. This reduces the power of the study to detect statistically significant differences. We assessed the trial as being at high risk of attrition, reporting, and other biases. The risks of performance and detection bias are unclear. Overall, we judged the evidence to be of very low‐certainty.
Potential biases in the review process
The review authors may not be aware of individuals or organisations that have conducted or may be conducting relevant RCTs, therefore it is possible that relevant RCTs have not been identified.
Agreements and disagreements with other studies or reviews
A review examining IOP and glaucoma medications following ab interno trabecular bypass surgery with Trabectome was published recently (Kaplowitz 2016). This review included only prospective or retrospective case series or cohorts, so the results are not comparable with our review.
Study flow diagram.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1: phaco‐AIT versus phaco‐Trab, Outcome 1: Proportion of participants who were medication‐free at 12 months
Comparison 1: phaco‐AIT versus phaco‐Trab, Outcome 2: Mean change in IOP at 12 months
Comparison 1: phaco‐AIT versus phaco‐Trab, Outcome 3: Mean change in number of IOP‐lowering medications per day
Comparison 1: phaco‐AIT versus phaco‐Trab, Outcome 4: Proportion of participants who achieved an IOP of 14 mmHg or less at 12 months
Comparison 1: phaco‐AIT versus phaco‐Trab, Outcome 5: Proportion of participants who achieved an IOP of 17 mmHg or less at 12 months
Comparison 1: phaco‐AIT versus phaco‐Trab, Outcome 6: Proportion of participants who achieved an IOP of 21 mmHg or less at 12 months
Comparison 1: phaco‐AIT versus phaco‐Trab, Outcome 7: Proportion of participants who required further glaucoma surgery, including laser, at 12 months
Comparison 1: phaco‐AIT versus phaco‐Trab, Outcome 8: Proportion of participants experiencing any intra‐ and postoperative complications
Comparison 1: phaco‐AIT versus phaco‐Trab, Outcome 9: Proportion of participants experiencing intra‐ and postoperative complications within 30 days postoperative
Comparison 1: phaco‐AIT versus phaco‐Trab, Outcome 10: Proportion of participants experiencing intra‐ and postoperative complications > 30 days postoperative
| Phaco‐AIT compared with Phaco‐Trab for open‐angle glaucoma | ||||||
| Patient or population: participants 40 to 85 years of age with open‐angle glaucoma Settings: eye service Intervention: phaco‐AIT: combined Trabectome and cataract extraction with intraocular lens insertion Comparison: phaco‐Trab: combined trabeculectomy with mitomycin C and cataract extraction with intraocular lens insertion | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Assumed risk (phaco‐Trab) | Corresponding risk (phaco‐AIT) | |||||
| Proportion of participants who were medication‐free (not using drops) at 12 months | 500 per 1000 | 700 per 1000 | OR 2.33 | 18 (1 RCT) | ⊕⊝⊝⊝ | |
| Mean change in IOP (mmHg) at 12 months | The mean change in IOP in the phaco‐Trab group was ‐6.4 (SD 8.7) mmHg | MD: 3.70 (95% CI ‐1.44 to 8.84) | 18 (1 RCT) | ⊕⊝⊝⊝ | ||
| Mean change in number of IOP‐lowering drops taken per day at 12 months | The mean change in the number of IOP‐lowering medications in the phaco‐Trab group was ‐0.51 SD 0.81) | MD: ‐0.41 (95% CI ‐1.22 to 0.40) | 18 (1 RCT) | ⊕⊝⊝⊝ | ||
| Proportion of participants who required further glaucoma surgery at 12 months | 1 participant required further glaucoma surgery in the phaco‐AIT group vs. none in the phaco‐Trab group (approximate OR 3.00, 95% CI 0.11 to 83.36) | 18 (1 RCT) | ⊕⊝⊝⊝ | |||
| Rate of visual field progression | The study protocol declared that this outcome was measured, but it was not reported | |||||
| Mean change in health‐related quality of life | The study protocol declared that this outcome was measured, but it was not reported | |||||
| Proportion of participants experiencing intra‐ and postoperative complications | Overall, 8 of 10 participants (80%) experienced any complication in the phaco‐AIT groups vs. 8 of 8 (100%) in the phaco‐Trab group. Data are sparse and effect estimates are extremely imprecise. Early and late postoperative complications are presented in the Effects of interventions. | ⊕⊝⊝⊝ | ||||
| *The assumed risk is the median risk in control groups in the included studies (rounded to nearest 10 per 1000). The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; IOP: intraocular pressure; MD: mean difference; OR: odds ratio; RCT: randomised controlled trial | ||||||
| GRADE Working Group grades of evidence High‐certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate‐certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low‐certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low‐certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | ||||||
| 1) downgraded ‐1 level for serious limitations in study design 2) downgraded ‐2 level for imprecision | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Proportion of participants who were medication‐free at 12 months Show forest plot | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.2 Mean change in IOP at 12 months Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.3 Mean change in number of IOP‐lowering medications per day Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.4 Proportion of participants who achieved an IOP of 14 mmHg or less at 12 months Show forest plot | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.5 Proportion of participants who achieved an IOP of 17 mmHg or less at 12 months Show forest plot | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.6 Proportion of participants who achieved an IOP of 21 mmHg or less at 12 months Show forest plot | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.7 Proportion of participants who required further glaucoma surgery, including laser, at 12 months Show forest plot | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.8 Proportion of participants experiencing any intra‐ and postoperative complications Show forest plot | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.9 Proportion of participants experiencing intra‐ and postoperative complications within 30 days postoperative Show forest plot | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.10 Proportion of participants experiencing intra‐ and postoperative complications > 30 days postoperative Show forest plot | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
