Device modified trabeculectomy for glaucoma

  • Protocol
  • Intervention

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

The primary objective of this systematic review of modified trabeculectomy for glaucoma is to assess the effectiveness of the use of different devices with standard trabeculectomy on IOP control in patients with glaucoma. We will also assess the safety of the interventions by a review of all adverse events occurring during and after the intervention.

Background

Description of the condition

Glaucoma is an optic neuropathy that leads to vision loss and blindness (Foster 2002). Among the many known and unknown factors that contribute to the damage to the optic nerve, elevated intraocular pressure (IOP) is the only modifiable risk factor (Coleman 2012). Normally, the IOP is maintained in balance when the rate of aqueous production by the ciliary body is equal to the rate of its outflow from the posterior to the anterior chamber through the trabecular meshwork and the canal of Schlemm in the anterior chamber angle (Small 1986). When excess aqueous humor is produced or when part or all of the drainage system of aqueous humor is blocked, the result is an increase in IOP, which has been shown to be associated with progressive glaucomatous optic nerve damage (Pan 2011; Turkoski 2012).

There are several types of glaucoma, of which open angle glaucoma (OAG) and angle closure glaucoma (ACG) are the two major types.

Epidemiology

The World Health Organization (WHO) has estimated that glaucoma is the second leading cause of blindness worldwide (Quigley 2011). It has been estimated that there were 60.5 million people with OAG and ACG in 2010, and the number will increase globally to 79.6 million by 2020. The most common type of glaucoma is OAG, accounting for 74% of glaucoma cases worldwide. ACG is less common and its cause is often genetic. Women comprise 55% of OAG, 70% of ACG, and 59% of all glaucoma cases. Asians represent 47% of those with glaucoma and 87% of those with ACG (Quigley 2006).

Symptoms and diagnosis

OAG is often asymptomatic initially. There is no pain and affected patients tend not to notice loss of visual field until the central vision area is affected in the later stage of the disease; by then optic nerve damage is often already severe (Boland 2008; Quigley 2011; Small 1986). The symptoms for ACG vary. It may occur without warning or with gradual deterioration; patients may have signs including severe pain and red eye, decreased or cloudy vision, nausea, vomiting, and bradycardia (Boland 2008; Douglas 1975; Small 1986). Clinical examinations for diagnosing glaucoma include, but are not limited to, tonometry, gonioscopy, optic nerve imaging, visual acuity, and visual field assessment.

Description of the intervention

Trabeculectomy, first introduced by John Cairns in 1968 and then modified by Watson in 1972, remains the gold standard and the most common incisional surgical procedure for the treatment of glaucoma (Cairns 1968; Watson 1972; Watson 1981). It includes lifting the conjunctiva and dissecting a partial thickness scleral flap and then a perforating scleral entrance into the anterior chamber to allow aqueous drainage, and it may also include removing part of the eye's trabecular meshwork and adjacent structures. This can lower IOP effectively by allowing aqueous fluid to percolate through the scleral hole or the cut ends of the trabecular meshwork into the subconjunctival space. Over the years trabeculectomy has been modified in various ways, including the use of 5-fluorouracil (5-FU) (Wormald 2001) and mitomycin C (MMC) (Wilkins 2005), and a fornix-based rather than a traditional limbus-based conjunctival flap. Most recently, the modifications have included devices in a standard trabeculectomy. They either use a tube without a reservoir (for example, Ex-PRESS) or a space-holder or reservoir (for example, OloGen) to enhance outflow or modify healing and promote continued drainage from the anterior chamber through a standard partial thickness scleral flap used in a standard trabeculectomy.

How the intervention might work

Antimetabolites and biodegradable implant (OloGen)

Wound healing and scar formation are the main problems of a standard trabeculectomy. They may lead to fibrosis of the bleb (bubble-like blister of the conjunctiva) and obstruction of the drainage fistula, and finally cause bleb failure (Skuta 1987). Antifibrotic agents, such as 5-FU and MMC, have been demonstrated to be effective in delaying wound healing and thus improving the success rate of trabeculectomy (Azuara-Blanco 1998; Fraser 2004). Therefore, 5-FU and MMC have become widely utilized as adjuncts with glaucoma filtering surgery. However, although 5-FU and MMC improve the success of trabeculectomy, there has been increased concern about the complications associated with antimetabolites, for example bleb-related infections, bleb leaks, and bleb dysesthesia (defined as burning, foreign body sensation, tearing, pain, or ocular discomfort in an eye with a filtering bleb) (Bell 1997; Jampel 1992; Lama 2003).

The OloGen implant is a plate-shaped, tissue bioengineered, biodegradable porous collagen-glycosaminoglycan matrix used during trabeculectomy. The device can randomly reorganize the regeneration of myofibroblasts, fibroblasts, and the secreted extracellular matrix, and consequently reduce the postoperative scar formation (Dietlein 2008). Recently, studies in animal models and several randomized clinical trials have reported that OloGen implanted in the subconjunctival space can provide an alternative method for controlling the wound-healing process and to avoid the complications of using antifibrotic agents (Chen 2006; Cillino 2011; Hsu 2008; Papaconstanitinou 2010; Rosentreter 2010).

Tube implant

1. Ex-PRESS mini glaucoma implant

Aiming at promoting continued aqueous drainage, the Ex-PRESS implant is a miniature stainless steel shunt developed recently as an alternative to trabeculectomy. The device is implanted under a partial thickness scleral flap to allow aqueous humor to flow from the anterior chamber to the subconjunctival space and leads to the formation of a thin-walled filtration bleb, similar to the process in a standard trabeculectomy. It has been reported in recent years, in both retrospective studies and randomized clinical trials, that the Ex-PRESS shunt provides better or similar IOP control as a trabeculectomy, and results in a lower rate of complications, fewer postoperative surgical interventions, and less need for glaucoma medications (Dahan 2012; de Jong 2009; de Jong 2011; Francis 2011; Gallego-Pinazo 2009; Maris 2007).

2. Silicon tube implant

Jordan et al reported the use of a silicon tube implant for the suprachoroidal drainage during a standard trabeculectomy approach (Jordan 2006). The tube was inserted as a junction connecting the anterior chamber and the suprachoroidal space, and it proved to be a new effective surgical technique option to treat intractable glaucoma. However, randomized controlled trials on the effectiveness and safety of a silicon tube have not been reported to date.

Other implants

Other than the most recent widely used OloGen and ExPRESS devices, there are other new devices being developed or being studied, including the SKgel and T-flux for non-penetrating glaucoma surgeries. Below are the devices reported to have been used in a trabeculectomy approach.

1. Expanded polytetrafluoroethylene (E-PTFE) membrane implant

E-PTFE is an expanded polytetrafluoroethylene implant made up of solid nodes inter-connected by a thin fibril matrix. Its use has been reported in several animal studies and human trials in the form of either a membrane patch or implant placed beneath the partial thickness scleral flap (Bae 1988; Cillino 2008; Jacob 2001) or combined with a silicone tube (Choi 2003; Kim 2003) shunt. Similarly, data from randomized controlled trials were scarce.

2. SOLX Gold Shunt

The SOLX Gold Shunt is a new biocompatible device made of pure gold (24-carat) that can reduce IOP utilizing the eye's natural pressure difference (http://www.solx.com/content/solx-gold-shunt). Through a special corneal or scleral incision, the device is inserted into the anterior chamber with the posterior end left in the suprachoroidal space. The device is currently approved for use in Canada and a few countries in Europe, and is under a multi-center clinical trial in the United States. No trial data have been published to date.

Why it is important to do this review

The purpose of this review is to compare the effectiveness and safety of modified trabeculectomy procedures versus standard trabeculectomy in the surgical treatment of glaucoma. We will also consider the use of antifibrotic agents and compare the surgical procedures when 5-FU or MMC is used by patients. Modified trabeculectomy is a relatively new procedure; therefore, individual studies do not report a large sample size or the study designs do not provide enough evidence of the effectiveness and safety of modified trabeculectomy procedures. In addition, there are no known systematic reviews assessing the effectiveness and safety of modified trabeculectomy devices in surgical therapy for glaucoma. Therefore, it becomes important to seek evidence across studies and to analyze effects of different devices in trabeculectomy on IOP control.

Objectives

The primary objective of this systematic review of modified trabeculectomy for glaucoma is to assess the effectiveness of the use of different devices with standard trabeculectomy on IOP control in patients with glaucoma. We will also assess the safety of the interventions by a review of all adverse events occurring during and after the intervention.

Methods

Criteria for considering studies for this review

Types of studies

We will include only randomized controlled trials in this review.

Types of participants

We will include trials in which the participants were older than 18 years of age and were diagnosed with glaucoma, irrespective of their lens status. We will include all types of glaucoma (for example, primary open angle glaucoma, angle-closure glaucoma, pigmentary glaucoma, exfoliation glaucoma, and secondary glaucoma such as neovascular glaucoma) except pediatric and congenital glaucoma. There will be no restrictions with regard to patient gender, ethnicity, co-morbidities, use of adjunctive medications, or the numbers of participants enrolled. Studies with participants all under 18 years of age will be excluded as pediatric glaucoma and congenital glaucoma are not the purpose of this review.

Types of interventions

All trials that compared a modified trabeculectomy device (with or without the use of antimetabolites) with a standard trabeculectomy will be included. The devices we intend to assess in this review include the: Ex-PRESS, OloGen, Silicone tube implant, e-PTFE, and SOLX Gold Shunt, which are all the major devices popularly used in glaucoma surgeries and can be employed under a standard trabeculectomy flap. We will also include other devices when any new implants are developed and utilized in a trabeculectomy. In summary, we will include the following comparisons:

  1. trabeculectomy + device (any of the above described) versus trabeculectomy;

  2. trabeculectomy + device (Ologen) versus trabeculectomy + antimetabolites (MMC or 5-FU, or both);

  3. trabeculectomy + device (any of the above described) + antimetabolites (MMC or 5-FU, or both) versus trabeculectomy + antimetabolites (MMC or 5-FU, or both).

There are two pairs of comparisons that we will not include in this review as there are other Cochrane reviews covering these topics:

  1. the adjudication of MMC and 5-FU compared to a standard trabeculectomy (Clarke 2006);

  2. the comparison of fornix-based (the modification) and traditional limbus-based trabeculectomy (Al-Haddad 2011).

In addition, studies in which combined trabeculectomy and cataract surgery was performed or was permitted will not be included as this is not the scope of this review.

Types of outcome measures

Primary outcomes

The primary outcomes of this review will be as follows.

  1. Change of IOP, measured as a mean decrease (or percentage decrease, as data are available) from baseline (immediate preoperative IOP) at one year after the intervention and measured using Goldmann tonometry, TonoPen, or other standard device.

  2. IOP fluctuation, assessed as a standard deviation or range of IOP before or one year after the procedure, if it is available.

Secondary outcomes
  1. Mean change of IOP from baseline, measured on day one, during weeks one to 12, at four to six months, seven to 12 months, as available throughout follow up, and at last follow up.

  2. Best corrected visual acuity (BCVA), measured by Snellen chart or Snellen equivalent and assessed at one year post-intervention. We will consider BCVA measured as a continuous outcome or a dichotomous outcome defined as loss of vision of more than two lines from the preoperative level, as data are available.

  3. Visual field change, measured in units of mean deviation or mean defect (MD) at one year post-intervention, the average pointwise difference between a given test result and the normal age matched reference value.

  4. Quality of life, measured by the National Eye Institute Visual Function Questionnaire (NEI VFQ) or any other available validated measurements at one year post-intervention.

  5. Frequency of the following complications: loss of vision more than two lines, IOP < 5 mmHg (hypotony), surgical revision within three months and one year after surgery, endophthalmitis or blebitis, retinal detachment, corneal transplant, cataract extraction (in those who have not had prior cataract extraction), choroidal hemorrhage, and others as available in the included studies.

Search methods for identification of studies

Electronic searches

We will search the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, EMBASE, Latin American and Caribbean Literature on Health Sciences (LILACS), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We will not use any date or language restrictions in the electronic search for trials.

See: Appendices for details of search strategies for CENTRAL (Appendix 1), MEDLINE (Appendix 2), EMBASE (Appendix 3), LILACS (Appendix 4), mRCT (Appendix 5), ClinicalTrials.gov (Appendix 6) and the ICTRP (Appendix 7).

Searching other resources

We will search the references of included studies for additional relevant studies, without restrictions regarding language or date of publication.

Data collection and analysis

Selection of studies

Two authors will independently review the titles and abstracts of all reports identified through the electronic and manual searches. The titles and abstracts will be classified as 'definitely include', 'unsure', or 'definitely exclude'. We will retrieve full text articles for those classified as 'definitely include' or 'unsure', and two authors will re-assess them as 'definitely include' or 'definitely exclude'. We will resolve disagreements by discussion. When resolution is not possible, we will consult a third review author. All publications from studies meeting the inclusion criteria will then undergo assessment of risk of bias and data extraction. We will exclude studies classified as 'definitely exclude', and will record the reason for exclusion in the 'Characteristics of excluded studies' table.

Data extraction and management

Two review authors will independently extract the data for the primary and secondary outcomes onto paper data collection forms developed in collaboration with the Cochrane Eyes and Vision Group. We will resolve discrepancies by discussion. If consensus is not reached, we will consult a third review author. One review author will enter data into RevMan 5.2 (RevMan 2012) and a second review author will verify the data.

Assessment of risk of bias in included studies

Two review authors will independently assess the risk of bias of included studies as part of the data extraction process. We will follow the tools for assessing risk of bias set forth in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a).

We will apply seven main quality criteria:

  1. sequence generation;

  2. allocation concealment;

  3. masking of participants, personnel, and outcome assessors;

  4. incomplete outcome data;

  5. selective outcome reporting;

  6. funding source;

  7. other sources of bias.

We will assess the trials for each quality criterion, as high risk of bias, low risk of bias, or unclear risk of bias (lack of information or uncertainty over the potential for bias).

Measures of treatment effect

Dichotomous outcome

We will analyze visual acuity (loss of vision of more than two lines from preoperative level) using summary risk ratios with 95% confidence intervals, as data are available.

Continuous outcomes

We plan to estimate mean change from baseline to follow up with 95% confidence intervals (IOP, quality of life, and visual field change). We will calculate standardized mean differences (SMDs) when continuous outcomes are measured using different scales. We will also record IOP fluctuation and visual acuity as continuous outcomes when data are available.

Unit of analysis issues

For change of IOP, IOP fluctuation, and visual field the unit of analysis will be the eye. If any trial randomizes eyes in participants to a modified trabeculectomy (paired) versus a standard trabeculectomy, we will refer to Chapter 16 of the Cochrane Handbook for Systematic Reviews of Interventions as a guide for any intra-person correlation between eyes (Higgins 2011b). For data on quality of life and potential complications of therapy, the unit of analysis will be the individual.

Dealing with missing data

We will contact study investigators to request missing data or information, including but not limited to study methods, effect estimates, and standard deviations of the interventions. When the investigators do not respond within six weeks or with three attempts to contact, we will use the data as available. We will also refer to guidelines in Chapter 16 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011b) for handling missing data.

Assessment of heterogeneity

We will use the I2 statistic (%) to determine the proportion of variation due to heterogeneity, with a value above 50% suggesting substantial statistical heterogeneity. We will also examine both clinical and methodological heterogeneity of included studies and present the variability in the text.

Assessment of reporting biases

We plan to investigate whether our review is subject to reporting biases. We will use funnel plots to examine signs of asymmetry, in RevMan.

Data synthesis

We will determine whether data synthesis in meta-analyses can be done depending on the heterogeneity calculated. Whenever the I2 statistic suggests a substantial statistical heterogeneity, we will present results in a narrative summary. If the I2 statistic is less than 50% (indicating there is no substantial heterogeneity), we will combine the study results. If the number of included studies is small (three or fewer), we will use a fixed-effect model, otherwise we will use a random-effects model.

Subgroup analysis and investigation of heterogeneity

When studies stratify participants based on the status of the lens (that is, eyes that possess their natural lens (phakic), eyes without the crystalline lens (aphakic, as after cataract extraction), or eyes with an intraocular lens implanted that replaced the eye's natural lens (pseudophakic)), we will examine the results of these subgroups (phakic versus aphakic or pseudophakic). We also will examine subgroup findings by ethnicity, baseline IOP, and type of glaucoma if there are sufficient data.  

Sensitivity analysis

We will conduct sensitivity analyses to determine the impact of excluding studies with lower methodological quality, including exclusion of industry-funded studies and unpublished studies.

Acknowledgements

We acknowledge Lori Rosman, Trials Search Co-ordinator for the US Satellite of the Cochrane Eyes and Vision Group (CEVG), for developing the search strategy and executing the electronic searches. We also acknowledge the CEVG editorial team and the peer reviewers Barbara Hawkins and Steve Mansberger for their support and insightful comments during the preparation of this protocol.

Richard Wormald (Co-ordinating Editor for CEVG) acknowledges financial support for his CEVG research sessions from the Department of Health through the award made by the National Institute for Health Research to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Specialist Biomedical Research Centre for Ophthalmology. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health.

Appendices

Appendix 1. CENTRAL search strategy

#1 MeSH descriptor: [Trabeculectomy] explode all trees
#2 MeSH descriptor: [Glaucoma] explode all trees and with qualifiers: [Surgery - SU]
#3 MeSH descriptor: [Trabecular Meshwork] explode all trees and with qualifiers: [Surgery - SU]
#4 MeSH descriptor: [Filtering Surgery] explode all trees
#5 Trabeculectom* or Trabeculoplast* or Trabeculotom* or Goniotom* or Microtrabeculectom*
#6 (Glaucoma* near/5 (surg* or filter* or filtrate*))
#7 #1 or #2 or #3 or #4 or #5 or #6
#8 MeSH descriptor: [Glaucoma Drainage Implants] explode all trees
#9 (modif* near/5 (Trabeculectom* or Trabeculoplast* or Trabeculotom* or Goniotom* or Microtrabeculectom*))
#10 MeSH descriptor: [Polytetrafluoroethylene] explode all trees
#11 (Polytef or Politef or "E PTFE" or EPTFE or PTFE or TFE or FEP or SOLX or polytetrafluoroethylen* or polytetrafluorethylen* or polytetrafluoroethen* or Fluoroflex or Fluoroplast or Ftoroplast or Halon or Polyfene or Tetron or Tarflen or "GORE TEX" or Goretex or gortex or Teflon or Fluon or Ex-press or ologen or Baerveldt or Krupin or Ahmed or Molteno or ExPress or collagen matrix or collagen-GAG or collagen-glycosaminoglycan copolymer matrix)
#12 Device* or implant* or shunt* or valve* or tube*
#13 #8 or #9 or #10 or #11 or #12
#14 MeSH descriptor: [Fluorouracil] explode all trees
#15 5FU or 5-FU or Fluorouracil* or Fluoruracil* or 5-HU or Adrucil or Carac or Efudix or Fluoro Uracile or Fluoro-Uracile or Efudex or Fluoroplex or Flurodex or Fluracedyl or Haemato-fu or Neofluor or Onkofluor or Ribofluor or 5-Fluorouracil
#16 MeSH descriptor: [Mitomycin] explode all trees
#17 Mitomycin* or NSC-26980 or NSC 26980 or NSC26980 or Mutamycin or Ametycine or Mitocin-C or MitocinC or mytomycin* or mitomicin* or mytomicin* or MMC
#18 MeSH descriptor: [Mitomycins] explode all trees
#19 #18 from 1966 to 1991
#20 MeSH descriptor: [Antimetabolites] explode all trees
#21 MeSH descriptor: [Antimetabolites, Antineoplastic] explode all trees
#22 MeSH descriptor: [Nucleic Acid Synthesis Inhibitors] explode all trees
#23 Antimetabolite* or anti-metabolite*
#24 Antifibrotic* or anti-fibrotic*
#25 #14 or #15 or #16 or #17 or #19 or #20 or #21 or #22 or #23 or #24
#26 #7 and (#13 or #25)

Appendix 2. MEDLINE (OvidSP) search strategy

1. Randomized Controlled Trial.pt.
2. Controlled Clinical Trial.pt.
3. (randomized or randomised).ab,ti.
4. placebo.ab,ti.
5. drug therapy.fs.
6. randomly.ab,ti.
7. trial.ab,ti.
8. groups.ab,ti.
9. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8
10. exp animals/ not humans.sh.
11. 9 not 10
12. exp Trabeculectomy/
13. exp Glaucoma/su [Surgery]
14. exp Trabecular Meshwork/su [Surgery]
15. (Trabeculectom* or Trabeculoplast* or Trabeculotom* or Goniotom* or Microtrabeculectomy).tw.
16. (Glaucoma$ adj5 (surg$ or filter$ or filtrat$)).tw.
17. exp filtering surgery/
18. 12 or 13 or 14 or 15 or 16 or 17
19. exp Glaucoma Drainage Implants/
20. (modif* adj5 (Trabeculectom* or Trabeculoplast* or Trabeculotom* or Goniotom* or Microtrabeculectomy)).tw.
21. exp Polytetrafluoroethylene/
22. (Polytef or Politef or "E PTFE" or EPTFE or PTFE or TFE or FEP or SOLX or polytetrafluoroethylen* or polytetrafluorethylen* or polytetrafluoroethen* or Fluoroflex or Fluoroplast or Ftoroplast or Halon or Polyfene or Tetron or Tarflen or "GORE TEX" or Goretex or gortex or Teflon or Fluon or Ex-press or ologen or Baerveldt or Krupin or Ahmed or Molteno or ExPress or collagen matrix or collagen-GAG or collagen-glycosaminoglycan copolymer matrix).tw.
23. (Device* or implant* or shunt* or valve* or tube*).tw.
24. 19 or 20 or 21 or 22 or 23
25. exp Fluorouracil/
26. (5FU or 5-FU or Fluorouracil* or Fluoruracil* or 5-HU or Adrucil or Carac or Efudix or Fluoro Uracile or Fluoro-Uracile or Efudex or Fluoroplex or Flurodex or Fluracedyl or Haemato-fu or Neofluor or Onkofluor or Ribofluor or 5-Fluorouracil).tw.
27. exp Mitomycin/
28. (Mitomycin* or NSC-26980 or NSC 26980 or NSC26980 or Mutamycin or Ametycine or Mitocin-C or MitocinC or mytomycin* or mitomicin* or mytomicin* or MMC).tw.
29. exp Mitomycins/
30. limit 29 to yr="1966 - 1991"
31. antimetabolites/
32. Antimetabolites, Antineoplastic/
33. Nucleic Acid Synthesis Inhibitors/
34. (Antimetabolite* or anti-metabolite*).tw.
35. (Antifibrotic* or anti-fibrotic*).tw.
36. 25 or 26 or 27 or 28 or 30 or 31 or 32 or 33 or 34 or 35
37. 11 and 18 and (24 or 36)

The search filter for trials at the beginning of the MEDLINE strategy is from the published paper by Glanville et al (Glanville 2006).

Appendix 3. EMBASE.com search strategy

1. 'randomized controlled trial'/exp
2. 'randomization'/exp
3. 'double blind procedure'/exp
4. 'single blind procedure'/exp
5. random*:ab,ti
6. 1 OR 2 OR 3 OR 4 OR 5
7. 'animal'/exp OR 'animal experiment'/exp
8. 'human'/exp
9. 7 AND 8
10. 7 NOT 9
11. 6 NOT 10
12. 'clinical trial'/exp
13. (clin* NEAR/3 trial*):ab,ti
14. ((singl* OR doubl* OR trebl* OR tripl*) NEAR/3 (blind* OR mask*)):ab,ti
15. 'placebo'/exp
16. placebo*:ab,ti
17. random*:ab,ti
18. 'experimental design'/exp
19. 'crossover procedure'/exp
20. 'control group'/exp
21. 'latin square design'/exp
22. 12 OR 13 OR 14 OR 15 OR 16 OR 17 OR 18 OR 19 OR 20 OR 21
23. 22 NOT 10
24. 23 NOT 11
25. 'comparative study'/exp
26. 'evaluation'/exp
27. 'prospective study'/exp
28. control*:ab,ti OR prospectiv*:ab,ti OR volunteer*:ab,ti
29. 25 OR 26 OR 27 OR 28
30. 29 NOT 10
31. 30 NOT (11 OR 23)
32. 11 OR 24 OR 31
33. 'trabeculectomy'/exp
34. 'trabeculoplasty'/exp
35. 'trabeculotomy'/exp
36. trabeculectom*:ab,ti OR trabeculoplast*:ab,ti OR trabeculotom*:ab,ti OR goniotom*:ab,ti OR microtrabeculectom*:ab,ti
37. 'glaucoma surgery'/de
38. 'trabecular meshwork'/exp
39. (glaucoma* NEAR/5 (surg* OR filter* OR filtrate*)):ab,ti
40. 'filtering operation'/de
41. 33 OR 34 OR 35 OR 36 OR 37 OR 38 OR 39 OR 40
42. 'glaucoma drainage implant'/exp
43. (modif* NEAR/5 (trabeculectom* OR trabeculoplast* OR trabeculotom* OR goniotom* OR microtrabeculectom*)):ab,ti
44. 'politef'/exp
45. (Polytef or Politef or 'E PTFE' or EPTFE or PTFE or TFE or FEP or SOLX or polytetrafluoroethylen* or polytetrafluorethylen* or polytetrafluoroethen* or Fluoroflex or Fluoroplast or Ftoroplast or Halon or Polyfene or Tetron or Tarflen or 'GORE TEX' or Goretex or gortex or Teflon or Fluon or Ex-press or ologen or Baerveldt or Krupin or Ahmed or Molteno or ExPress or 'collagen matrix' or 'collagen-GAG' or 'collagen-glycosaminoglycan copolymer matrix'):ab,ti
46. device*:ab,ti OR implant*:ab,ti OR shunt*:ab,ti OR valve*:ab,ti OR tube*:ab,ti
47. 42 OR 43 OR 44 OR 45
48. 'fluorouracil'/exp
49. 5fu:ab,ti OR '5 fu':ab,ti OR fluorouracil*:ab,ti OR fluoruracil*:ab,ti OR '5 hu':ab,ti OR adrucil:ab,ti OR carac:ab,ti OR efudix:ab,ti OR fluoro:ab,ti AND uracile:ab,ti OR 'fluoro uracile':ab,ti OR efudex:ab,ti OR fluoroplex:ab,ti OR flurodex:ab,ti OR fluracedyl:ab,ti OR 'haemato fu':ab,ti OR neofluor:ab,ti OR onkofluor:ab,ti OR ribofluor:ab,ti OR '5 fluorouracil':ab,ti OR '5 fluoro 2':ab,ti OR '4 pyrimidinedione':ab,ti OR '5 fu':ab,ti OR accusite:ab,ti OR 'actino hermal':ab,ti OR effluderm:ab,ti OR efurix:ab,ti OR f6627:ab,ti OR fivoflu:ab,ti OR fluoroblastin:ab,ti OR fluouracil:ab,ti OR fluoxan:ab,ti OR fluracil:ab,ti OR fluracilium:ab,ti OR fluril:ab,ti OR 'fluro uracil':ab,ti OR fluroblastin:ab,ti OR ifacil:ab,ti OR 'nsc 18913':ab,ti OR 'nsc 19893':ab,ti OR 'nsc18913':ab,ti OR nsc19893:ab,ti OR 'oncofu':ab,ti OR 'ro 2-9757':ab,ti OR 'ro 2 9757':ab,ti OR 'ro2-9757':ab,ti OR 'ro2 9757':ab,ti OR uflahex:ab,ti OR utoral:ab,ti OR verrumal:ab,ti OR '51 21 8':ab,ti
50. 'mitomycin'/exp
51. mitomycin*:ab,ti OR 'nsc 26980':ab,ti OR nsc:ab,ti AND 26980:ab,ti OR nsc26980:ab,ti OR mutamycin:ab,ti OR ametycine:ab,ti OR 'mitocin c':ab,ti OR mitocinc:ab,ti OR mytomycin*:ab,ti OR mitomicin*:ab,ti OR mytomicin*:ab,ti OR mmc:ab,ti OR datisan:ab,ti OR metomit:ab,ti OR mitocyna:ab,ti OR mitosol:ab,ti OR mixandex:ab,ti OR mytocine:ab,ti OR mytozytrex:ab,ti OR vetio:ab,ti OR '1404 00 8':ab,ti
52. 'antimetabolite'/de
53. 'antineoplastic antimetabolite'/de
54. 'nucleic acid synthesis inhibitor'/de
55. antimetabolite*:ab,ti OR (anti NEAR/1 ametabolite*):ab,ti
56. antifibrotic*:ab,ti OR (anti NEAR/1 fibrotic*):ab,ti
57. 48 OR 49 OR 50 OR 51 OR 52 OR 53 OR 54 OR 55 OR 56
58. 32 AND 41 AND (47 OR 57)

Appendix 4. LILACS search strategy

Trabeculectom$ or Trabeculoplast$  or Trabeculotom$ or Goniotom$ or Microtrabeculectom$ or "trabecular meshwork" or "filtering surgery" or glaucoma$
AND
Polytef or Politef or "E PTFE"or EPTFE or PTFE or TFE or FEP or SOLX or polytetrafluoroethylen$ or polytetrafluorethylen$ or polytetrafluoroethen$ or Fluoroflex or Fluoroplast or Ftoroplast or Halon or Polyfene or Tetron or Tarflen or "GORE TEX" or Goretex or gortex or Teflon or Fluon or Ex-press or ologen or Baerveldt or Krupin or Ahmed or Molteno or ExPress or "collagen matrix" or "collagen-GAG" or "collagen-glycosaminoglycan copolymer matrix" or Device$ or implant$ or shunt$ or valve$ or tube$ or (modif$ and Trabeculectom$ or Trabeculoplast$ or Trabeculotom$ or Goniotom$ or Microtrabeculectom$) or Fluorouracil$ or 5FU or 5-FU or Fluoruracil$ or 5-HU or Adrucil or Carac or Efudix or Fluoro Uracile or Fluoro-Uracile or Efudex or Fluoroplex or Flurodex or Fluracedyl or Haemato-fu or Neofluor or Onkofluor or Ribofluor or  5-Fluorouracil or Mitomycin$ or NSC-26980 or NSC 26980 or NSC26980 or Mutamycin or Ametycine or Mitocin-C or MitocinC or mytomycin$ or mitomicin$ or mytomicin$ or MMC  or Antimetabolite$ or anti-metabolite$ or Antifibrotic$ or anti-fibrotic$

Appendix 5. metaRegister of Controlled Trials search strategy

(Trabeculectomy OR (glaucoma surgery)) AND (device OR implant OR implants OR shunt OR valve OR tube OR 5FU OR 5-FU OR Fluorouracil OR Fluoruracil OR Fluoro Uracile OR 5-Fluorouracil OR Mitomycin OR MMC OR Antimetabolite OR Antimetabolites OR Antifibrotic)

Appendix 6. ClinicalTrials.gov search strategy

(search terms) Trabeculectomy OR Trabeculoplasty OR Trabeculotomy OR Goniotomy OR Microtrabeculectomy OR glaucoma

(intervention) Device OR implant OR implants OR shunt OR valve OR tube OR Fluorouracil OR 5- Fluorouracil OR 5-FU OR Fluoruracil OR Mitomycin OR mytomycin OR mitomicin OR mytomicin OR MMC OR Antimetabolite OR Antifibrotic

Appendix 7. ICTRP search strategy

(condition) Trabeculectomy OR Trabeculoplasty OR Trabeculotomy OR Goniotomy OR Microtrabeculectomy OR Goniotomy OR Microtrabeculectomy OR glaucoma

(intervention) Device OR implant OR implants OR shunt OR valve OR tube OR Fluorouracil OR 5- Fluorouracil OR 5-FU OR Fluoruracil OR Mitomycin OR mytomycin OR mitomicin OR mytomicin OR MMC OR Antimetabolite OR Antifibrotic

Contributions of authors

XW and AC conceived and designed the review. XW, AC, and RW wrote the protocol.

Declarations of interest

None known

Sources of support

Internal sources

  • No sources of support supplied

External sources

  • National Eye Institute, National Institutes of Health, USA.

    Xue Wang is funded by the Cochrane Eyes and Vision - US Project through the National Eye Institute Grant 1 U01 EY020522-01

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