Table 2 – Characteristics of 49 reliable systematic reviews on interventions for glaucoma conditions -.

sorted by intervention type and in reverse chronological order of publication.

Study ID [PMID] Title	Objective(s)	Participants	Intervention Comparisons	# of Studies; Participants (or eyes) [Study Types]	Conclusion(s)
Medical Interventions
Rennie 2019 [30880485] Topical medical therapy and ocular perfusion pressure in open angle glaucoma	“[To compare] the benefits and harms of topical interventions for ocular perfusion pressure in open angle glaucoma.”	Open angle glaucoma	Latanoprost; timolol; brimonidine; bimatoprost; dorzolamide; timogel; tafluprost; travaprost	10; 416 [RCT, CCT]	“We identified low to moderate quality evidence describing post-intervention mean ocular perfusion pressure in open angle glaucoma. Bimatoprost increases mean ocular perfusion pressure when compared to timolol. As a class, prostaglandins increase mean ocular perfusion pressure. Prostaglandins may provide beneficial ocular perfusion pressure profiles compared to alternative agents.”
Loskutova 2018 [30296451] Nutritional supplementation in the treatment of glaucoma	“To determine whether nutritional interventions intended to prevent or delay the progression of glaucoma could prove to be a valuable addition to the mainstay of glaucoma therapy.”	Non-specific glaucoma	Nutritional supplementation; placebo	21; 1935 [RCT, CCT, Cohort, Uncontrolled trial]	“Flavinoids [are suggested to] exert a beneficial effect in glaucoma, particularly in terms of improving ocular blood flow and potentially slowing progression of visual field loss. In addition, supplements containing forskolin have consistently demonstrated the capacity to reduce intraocular pressure beyond the levels achieved with traditional therapy alone; however, despite the strong theoretical rationale and initial clinical evidence for the beneficial effect of dietary supplementation as an adjunct therapy for glaucoma, the evidence is not conclusive.” “…the data from RCTs attempting to investigate the link between nutrition and glaucoma in humans are scarce, lacking in quality, and mostly inconclusive.”
Li 2018 [29144028] Efficacy and safety of different regimens for primary open-angle glaucoma or ocular hypertension	“To assess the efficacy and safety of different treatment regimes for glaucoma.”	Open angle glaucoma, ocular hypertension	Latanoprost; timolol; brimonidine; brinzolamide; travoprost; dorzolamide; bimaprost; pilocarpine; tafluprost; betaxolol; cartelol; unoprostone;	72; 19916 [RCT]	“Our network meta-analysis showed that prostaglandin analogues (PGAs) provide best intraocular pressure (IOP) lowering effect among all the monotherapy regimen.”
Huang 2018 [30142821] Safety of antivascular endothelial growth factor administration in the ocular anterior segment in pterygium and neovascular glaucoma treatment	“To compare anti-VEGF treatment in the ocular anterior segment in pterygium and neovascular glaucoma treatment with placebo/sham treatment for eye diseases.”	Neovascular glaucoma	Anti-VEGF; placebo	18 (5 for glaucoma); 955 eyes (266 for glaucoma) [RCT]	“The administration of anti-VEGF agents in the ocular anterior segment for patients with pterygium and glaucoma was tolerable in tolerance and cornea, but was the risk factor of conjunctival disorders. The healing of corneal epithelium may be delayed in patients with primary corneal epithelial defects after anti-VEGF application.” “However, due to the limited evidence, further research should be performed on the safety of anti-VEGF administration in patients with different corneal disorders”
Diaconita 2018 [30363694] Washout duration of prostaglandin analogues	“To investigate the long term effects on intraocular pressure (IOP) after discontinuation of topical prostaglandin analogues (PGAs) primary open angle glaucoma (POAG) and ocular hypertension (OHT) patients.”	Open angle glaucoma, ocular hypertension	Discontinuation of PGAs (latanoprost, unoprostone, travoprost, bimatoprost); continuing PGAs	8; 307 [RCT, CCT, Case series/report]	“A significant IOP-lowering effect of latanoprost was not observed beyond 4 weeks, suggesting this may be an appropriate washout period for latanoprost. We could not identify appropriate washout periods for either travoprost or bimatoprost, although a majority of articles had 4-week washout durations for the two drugs.”
Xu 2017 [28218404] Topical medication instillation techniques for glaucoma	“To investigate the effectiveness of topical medication instillation techniques compared with usual care or another method of instillation of topical medication in the management of glaucoma or ocular hypertension.”	Primary angle closure glaucoma, secondary glaucoma	Topical medication instillation; other methods of instillation of topical medication; usual care	2; 61 [RCT]	“Evidence to evaluate the effectiveness of topical medication instillation techniques for treatment of glaucoma is lacking. It is unclear what, if any, effects instillation techniques have on topical medical therapy for glaucoma.”
Sena 2017 [28122126] Neuroprotection for treatment of glaucoma in adults	“To systematically examine the evidence regarding the effectiveness of neuroprotective agents for slowing the progression of open-angle glaucoma in adults compared with no neuroprotective agent, placebo, or other glaucoma treatment.”	Open angle glaucoma	Brimonidine; timolol	1; 190 [RCT]	“Although the only trial we included in this review found less visual field loss in the brimonidine-treated group, the evidence was of such low certainty that we can draw no conclusions from this finding. Further clinical research is needed to determine whether neuroprotective agents may be beneficial for individuals with OAG.”
Li 2016 [26526633] Comparative effectiveness of first-line medications for primary open angle glaucoma	“To assess the comparative effectiveness of first line medical treatments in patients with Primary Open Angle Glaucoma (POAG) or ocular hypertension (OHT) through a systematic review and network meta-analysis, and to provide relative rankings of these treatments.”	Open angle glaucoma	Brimonidine; betaxolol; levobunolol; timolol; levobetaxolol; brinzolamide; dorzolamide; bimatoprost; unoprostone; latanoprost; travoprost; tafluprost; apraclonidine; carteolol; placebo	114; 20275 [RCT]	“All active first-line drugs are effective compared to placebo in reducing intraocular pressure (IOP) at 3 months. Bimatoprost, latanoprost, and travoprost are among the most efficacious drugs, although the within class differences were small and may not be clinically meaningful. All factors, including adverse effects, patient preferences, and cost should be considered in selecting a drug for a given patient.”
Liu 2016 [27275435] Long-term assessment of prostaglandin analogs and timolol fixed combinations prostaglandin analogs monotherapy	“To draw a Meta-analysis over the comparison of the intraocular pressure (IOP) lowering efficacy and safety between the commonly used fixed-combinations of prostaglandin analogs and 0.5% timolol with prostaglandin analogs (PGAs) monotherapy.”	Open angle glaucoma, ocular hypertension, primary angle closure glaucoma	Fixed combination latanoprost and timolol (morning); fixed combination latanoprost (morning); latanoprost (morning); bimatroprost (evening); fixed combination tafluprost and timolol (morning); tafluprost (morning)	5; 1981 [RCT]	“The long-term efficacy of the fixed combination of PGAs/timolol therapy (FCs) overweighed the PGAs monotherapy in lowering IOP, but in the incidence of hyperemia and eye irritation syndromes, the differences are not statically significant. More RCTs with detailed and authentic data over the assessments of visual functions and morphology of optic nerve heads are hoped to be conducted.”
Whiting 2015 [26103030] Cannabinoids for medical use	“To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids.”	Ocular pressure glaucoma	Medical cannabinoids; placebo	1; 6 [RCT]	“There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.”
Xing 2014 [25349811] Fixed combination of latanoprost and timolol the individual components for primary open angle glaucoma and ocular hypertension	“To assess the effects of the fixed combination of 0.005% latanoprost and 0.5% timolol (FCLT) their individual components for primary open angle glaucoma (POAG) and ocular hypertension (OHT).”	Open angle glaucoma, ocular hypertension	Fixed combination (latanoprost and timolol); timolol; latanoprost; unfixed combination (latanoprost and timolol)	14; 4135 [RCT, CCT]	“A better intraocular pressure (IOP) lowering effect has been demonstrated for FCLT compared to the monotherapy of components. The IOP lowering effect was worse for FCLT morning dose and almost same for FCLT evening dose compared to the unfixed combination of 0.005% latanoprost and 0.5% timolol (UFCLT). We need more long-term high quality RCTs to demonstrate the outcomes of visual field defect and optic atrophy.”
Lin 2014 [25184309] Comparative efficacy and tolerability of topical prostaglandin analogues for primary open-angle glaucoma and ocular hypertension	“To systematically review the efficacy and tolerability of 4 prostaglandin analogues (PGAs) as first-line monotherapies for intraocular pressure (IOP) lowering in adult patients with primary open-angle glaucoma or ocular hypertension.”	Open angle glaucoma, ocular hypertension	Bimatoprost; latanoprost; tafluprost; travoprost	32; 6565 [RCT]	“Bimatoprost achieved the highest efficacy in terms of IOP reduction, whereas latanoprost had the most favorable tolerability profile. This review serves to guide selection of the optimal PGA agent for individual patient care in clinical practice.”
Waterman 2013 [23633333] Interventions for improving adherence to ocular hypotensive therapy.	“To summarise the effects of interventions for improving adherence to ocular hypotensive therapy in people with ocular hypertension (OHT) or glaucoma.”	Ocular hypertension, non-specific glaucoma	Education; education with behavioural change; any intervention to improve adherence; brimonidine; dorzolamide; latanoprost; timolol; pilocarpine; usual care	16; 1565 [RCT, CCT]	“Although complex interventions consisting of patient education combined with personalised behavioural change interventions, including tailoring daily routines to promote adherence to eye drops, may improve adherence to glaucoma medication, overall there is insufficient evidence to recommend a particular intervention.”
Simha 2013 [24089293] Anti-vascular endothelial growth factor for neovascular glaucoma.	“To compare the intraocular pressure (IOP) lowering effects of intraocular anti-VEGF agents to no anti-VEGF treatment, as an adjunct to existing modalities for the treatment of Neovascular Glaucoma (NVG).”	Neovascular glaucoma	Anti-VEGF agents alone; anti-VEGF agents combined with any type of conventional therapy	0; 0 [NA]	“Currently available evidence is insufficient to evaluate the effectiveness of anti-VEGF treatments, such as intravitreal ranibizumab or bevacizumab, as an adjunct to conventional treatment in lowering IOP in NVG.”
Law 2013 [23728656] Acupuncture for glaucoma.	“To assess the effectiveness and safety of acupuncture in people with glaucoma.”	Non-specific glaucoma	Acupuncture; sham acupuncture	1; 33 [RCT, CCT]	“At this time, it is impossible to draw reliable conclusions from available data to support the use of acupuncture for the treatment of glaucoma. Because of ethical considerations, RCTs comparing acupuncture alone with standard glaucoma treatment or placebo are unlikely to be justified in countries where the standard of care has already been established. Because most glaucoma patients currently cared for by ophthalmologists do not use nontraditional therapy, clinical practice decisions will have to be based on physician judgments and patient preferences, given this lack of data in the literature.”
Burr 2012 [22972069] Medical versus surgical interventions for open angle glaucoma.	“To assess the effects of medication compared with initial surgery in adults with Open Angle Glaucoma (OAG).”	Open angle glaucoma	Medical treatment; trabeculectomy	4; 888 [RCT, CCT]	“Primary surgery lowers intraocular pressure more than primary medication but is associated with more eye discomfort. One trial suggests that visual field restriction at five years is not significantly different whether initial treatment is medication or trabeculectomy. There is some evidence from two small trials in more severe OAG, that initial medication (pilocarpine, now rarely used as first line medication) is associated with more glaucoma progression than surgery. Beyond five years, there is no evidence of a difference in the need for cataract surgery according to initial treatment. The clinical and cost-effectiveness of contemporary medication (prostaglandin analogues, alpha2-agonists and topical carbonic anhydrase inhibitors) compared with primary surgery is not known.”
Vass 2007 [17943780] Medical interventions for primary open angle glaucoma and ocular hypertension.	“To assess and compare the effectiveness of topical pharmacological treatment for Primary Open Angle Glaucoma (POAG) or ocular hypertension (OHT) to prevent progression or onset of glaucomatous optic neuropathy.”	Primary open angle glaucoma, ocular hypertension	Topical antiglaucomatous drugs (timolol, levobunolol, betaxolol, dorzolamide, carteolol, brimonidine, pilocarpine, epinephrine); unspecified topical antiglaucomatous drug; placebo; no treatment	26; 4979 [RCT]	“The results of this review support the current practice of intraocular pressure (IOP) lowering treatment of OHT. A visual field protective effect has been clearly demonstrated for medical IOP lowering treatment. Positive but weak evidence for a beneficial effect of the class of beta-blockers has been shown. Direct comparisons of prostaglandins or brimonidine to placebo are not available and the comparison of dorzolamide to placebo failed to demonstrate a protective effect. However, absence of data or failure to prove effectiveness should not be interpreted as proof of absence of any effect. The decision to treat a patient or not, as well as the decision regarding the drug with which to start treatment, should remain individualised, taking in to account the amount of damage, the level of IOP, age and other patient characteristics.”
Surgical interventions
Altmatlouh 2019 [30242968] Steroids and nonsteroidal anti-inflammatory drugs in the postoperative regime after trabeculectomy - which provides the better outcome?	“To compare the effectiveness of different formulations of steroids (topical, systemic and depot) and nonsteroidal anti-inflammatory drugs (NSAIDs) in achieving long-term pressure control with fewer antiglaucomatous medications, preserving visual acuity and visual fields while considering surgical and postoperative complications.”	Non-specific glaucoma patients undergoing trabeculectomy	Topical steroid; combined topical and oral steroid; combined topical and depot steroid; combined topical steroid and topical NSAID; topical NSAID; placebo	7; 437 (mix of participants and eyes in studies) [RCT]	“There is a low level of evidence to support the clinician in deciding which postoperative regime provides a more favourable outcome because of inconsistency in the reported outcomes between studies and a low number of patients for each comparable intervention and outcome. It does seem that topical steroids are better than no anti-inflammatory treatment after glaucoma surgery, but further research is recommended.”
Chen 2018 [29533959] Efficacy and safety of bevacizumab combined with mitomycin C or 5-fluorouracil in primary trabeculectomy	“To evaluate the efficacy and safety of bevacizumab combined with antimetabolite as an adjunctive therapy in primary trabeculectomy for glaucoma.”	Non-specific glaucoma patients undergoing primary trabeculectomy, excluding pediatric glaucoma	Trabeculectomy with mitomycin C (MMC) + bevacizumab; trabeculectomy with 5-Flourouracil (FU)+ bevacizumab; trabeculectomy with MMC; trabeculectomy with 5-FU	3; 141 [RCT]	“The systematic review demonstrated that the combination of bevacizumab (1.25 mg/mL) with a regular concentration of antimetabolite did not show more benefit or harm compared with using anti-metabolite alone.”
Cheng 2016 [26769010] Anti-vascular endothelial growth factor for control of wound healing in glaucoma surgery	“To assess the effectiveness of anti-vascular endothelial growth factor (VEGF) therapies administered by subconjunctival injection for the outcome of trabeculectomy at 12 months follow-up and to examine the balance of benefit and harms when compared to any other anti-scarring agents or no additional anti-scarring agents.”	Non-specific glaucoma patients undergoing trabeculectomy	Trabeculectomy with subconjunctival anti-VEGF; trabeculectomy with anti-scarring agents; trabeculectomy with no additional anti-scarring agents	5; 175 [RCT]	“The evidence is currently of low quality which is insufficient to refute or support anti-VEGF subconjunctival injection for control of wound healing in glaucoma surgery. The effect on intraocular pressure (IOP) control of anti-VEGF agents in glaucoma patients undergoing trabeculectomy is still uncertain, compared to mitomycin C (MMC).”
Zhang 2015 [26171900] Combined surgery versus cataract surgery alone for eyes with cataract and glaucoma	“To assess the relative effectiveness and safety of combined surgery versus cataract surgery (phacoemulsification) alone for co-existing cataract and glaucoma. The secondary objectives include cost analyses for different surgical techniques for co-existing cataract and glaucoma.”	Open angle glaucoma, pseudoexfoliative glaucoma, pigmentary glaucoma	Phacoemulsification; phacoemulsification and trabeculectomy; phacoemulsification and iStent; phacoemulsification and 2 iStents; phacoemulsification and trabecular aspiration; phacoemulsification and ab externo trabeculotomy	9; 655 [RCT]	“There is low quality evidence that combined cataract and glaucoma surgery may result in better intraocular pressure (IOP) control at one year compared with cataract surgery alone. The evidence was uncertain in terms of complications from the surgeries. Furthermore, this Cochrane review has highlighted the lack of data regarding important measures of the patient experience, such as visual field tests, quality of life measurements, and economic outcomes after surgery, and long-term outcomes (five years or more). Additional high-quality RCTs measuring clinically meaningful and patient-important outcomes are required to provide evidence to support treatment recommendations.”
Wang 2015 [26625212] Device-modified trabeculectomy for glaucoma	“To assess the relative effectiveness, primarily with respect to intraocular pressure (IOP) control and safety, of the use of different devices as adjuncts to trabeculectomy compared with standard trabeculectomy in eyes with glaucoma.”	Non-specific glaucoma	Trabeculectomy + MMC; trabeculectomy + MMC + ExPRESS; trabeculectomy + express under sclera; trabeculectomy + ExPRESS under conjunctiva; trabeculectomy + ExPPRESS; trabeculectomy + Ologen implant; trabeculectomy + amniotic membrane; trabeculectomy + MMC + amniotic membrane; trabeculectomy + EPTFE; trabeculectomy + MMC + EPTFE; trabeculectomy + Gelfilm; trabeculectomy + MMC + Gelfilm	33; 1542 [RCT]	“The use of devices with standard trabeculectomy may help with greater IOP reduction at one-year follow-up than trabeculectomy alone; however, due to potential biases and imprecision in effect estimates, the quality of evidence is low. When we examined outcomes within subgroups based on the type of device used, our findings suggested that the use of an Ex-PRESS device or an amniotic membrane as an adjunct to trabeculectomy may be slightly more effective in reducing IOP at one year after surgery compared with trabeculectomy alone. The evidence that these devices are as safe as trabeculectomy alone is unclear. Due to various limitations in the design and conduct of the included studies, the applicability of this evidence synthesis to other populations or settings is uncertain. Further research is needed to determine the effectiveness and safety of other devices and in subgroup populations, such as people with different types of glaucoma, of various races and ethnicity, and with different lens types (e.g. phakic, pseudophakic).”
Ghate 2015 [25636153] Surgical interventions for primary congenital glaucoma	“To compare the effectiveness and safety of different surgical techniques for primary congenital glaucoma.”	Primary congenital glaucoma	Trabeculotomy-trabeculectomy; trabeculectomy; viscocanalostomy; one goniotomy; two goniotomies; surgical goniotomy under general anesthesia; neodymium-YAG laser goniotomy under oral chloral hydrate sedation; combined trabeculectomy-trabeculotomy with MMC (CTTM); CTTM with deep sclerotomy	6; 61 [RCT]	“No conclusions could be drawn from the trials included in this review due to paucity of data. More research is needed to determine which of the many surgeries performed for primary congenital glaucoma are effective.”
Cabourne 2015 [26545176] Mitomycin C versus 5-fluorouracil for wound healing in glaucoma surgery	“To assess the effects of mitomycin compared to 5-Fluorouracil as an antimetabolite adjunct in trabeculectomy surgery.”	Non-specific glaucoma	Trabeculectomy with intraoperative MMC; trabeculectomy with intraoperative 5-FU; trabeculectomy with postoperative 5-FU; trabeculectomy with intraoperative and postoperative 5-FU; trabeculectomy with intraoperative and postoperative MMC	11; 679 [RCT]	“Low-quality evidence exists that mitomycin may be more effective in achieving long-term lower intraocular pressure than 5-Fluorouracil.”
Al-Haddad 2015 [26599668] Fornix-based versus limbal-based conjunctival trabeculectomy flaps for glaucoma	“To assess the comparative effectiveness of fornix-versus limbal-based conjunctival flaps in trabeculectomy for adult glaucoma, with a specific focus on intraocular pressure (IOP) control and complications (adverse effects).”	Non-specific glaucoma	Fornix-based trabeculectomy; limbal-based trabeculectomy	6; 361 [RCT]	“The main result of this review was that there was uncertainty as to the difference between fornix- and limbal-based trabeculectomy surgeries due to the small number of events and confidence intervals that cross the null. This also applied to postoperative complications, but without any impact on long-term failure rate between the two surgical techniques.”
Thomas 2014 [25066789] Antimetabolites in cataract surgery to prevent failure of a previous trabeculectomy	“To assess the effects of antimetabolites with cataract surgery on functioning of a previous trabeculectomy.”	Non-specific glaucoma	Lens extraction with antimetabolites (5-FU or MMC); lens extraction with no antimetabolites	0; 0 [NA]	“There are no RCTs of antimetabolites with cataract surgery in people with a functioning trabeculectomy. Appropriately powered RCTs are needed of antimetabolites during cataract surgery in patients with a functioning trabeculectomy.”
Green 2014 [24554410] 5-Fluorouracil for glaucoma surgery	“To assess the effects of both intraoperative application and postoperative injections of 5-Flouracil (FU) in eyes of people undergoing surgery for glaucoma at one year.”	Non-specific glaucoma	Glaucoma surgery with mitomycin C; glaucoma surgery with 5-Fluorouracil	12; 1319 [RCT]	“We concluded that the main benefit is for people at high risk of problems. There may be a smaller benefit for people at low risk of problems if 5-FU is given either as injections after surgery or during the operation. However, 5-FU was found to increase the risk of serious complications and so may not be worthwhile for the small benefit gained.” “The small but statistically significant reduction in surgical failures and intraocular pressure at one year in the primary trabeculectomy group and high-risk group must be weighed against the increased risk of complications and patient preference.”
Eldaly 2014 [24532137] Non-penetrating filtration surgery versus trabeculectomy for open-angle glaucoma	“To compare the effectiveness of non-penetrating trabecular surgery compared with conventional trabeculectomy in people with glaucoma.”	Open angle glaucoma	Trabeculectomy; viscocanalostomy; deep sclerotomy	5; 311 eyes [RCT, CCT]	“This review provides some limited evidence that control of intraocular pressure (IOP) is better with trabeculectomy than viscocanalostomy. For deep sclerectomy, we cannot draw any useful conclusions.”
Kirwan 2012 [22696336] Beta radiation for glaucoma surgery.	“To assess the effectiveness of beta radiation during glaucoma surgery (trabeculectomy).”	Non-specific glaucoma patients undergoing trabeculectomy	Trabeculectomy with beta radiation; trabeculectomy	4; 551 [RCT]	“Trabeculectomy with beta irradiation has a lower risk of surgical failure compared to trabeculectomy alone.”
Waboso 2012 [22895936] Needling for encapsulated trabeculectomy filtering blebs.	“The objective of this review was to assess the effects of needling encapsulated blebs on intraocular pressure.”	People with encapsulated trabeculectomy blebs	Bleb needling; digital massage and non-specific betablockers, with or without systemic carbonic anhydrase inhibitor	1; 25 [RCT, CCT]	“Evidence from one small trial suggests that needling of encapsulated trabeculectomy blebs is not better than medical treatment in reducing intraocular pressure.”
Bochmann 2012 [22972097] Interventions for late trabeculectomy bleb leak.	“To assess the effects of interventions for late trabeculectomy bleb leak.”	Patients with a late-onset (i.e. more than three months after glaucoma surgery) bleb leak after trabeculectomy, patients with a history of blebitis or endophthalmitis in whom the infection has been controlled	Amniotic membrane transplant; conjunctival advancement; any intervention to close a bleb leak	1; 30 [RCT, CCT]	“Although a variety of treatments have been proposed for bleb leaks, there is no evidence of their comparative effectiveness. The evidence in this review was provided by a single trial that compared two surgical procedures (conjunctival advancement and amniotic membrane transplant). The trial did show a superiority of conjunctival advancement, which was regarded as standard treatment, to amniotic membrane transplantation.”
Friedman 2006 [16856103] Lens extraction for chronic angle-closure glaucoma.	“To assess the effectiveness of lens extraction for chronic primary angle-closure glaucoma compared with other interventions for the condition in people without past history of acute-angle closure attacks.”	Primary angle closure glaucoma	Extracapsular cataract extraction (ECCE) with posterior chamber intraocular lens (PCIOL) implantation; limbal-based trabeculectomy; extracapsular cataract extraction (ECCE) with posterior chamber intraocular lens (PCIOL) implantation and additional goniosynechialysis	2; 49 [RCT, CCT, Cohort]	“There is no evidence from good quality randomized trials or non-randomized studies of the effectiveness of lens extraction for chronic primary angle-closure glaucoma.”
Wilkans 2005 [16235305] Intra-operative mitomycin C for glaucoma surgery.	“To assess the effects of intraoperative mitomycin C (MMC) compared to placebo or no adjunct in trabeculectomy.”	Neovascular glaucoma; congenital glaucoma; glaucoma secondary to intraocular inflammation; people with previous glaucoma drainage surgery, previous surgery involving anything more than trivial conjunctival incision, undergoing trabeculectomy with extra-capsular cataract extraction and intraocular lens implant, or undergoing primary trabeculectomy	Trabeculectomy with intraoperative MMC; trabeculectomy with no antimetabolite; trabeculectomy with placebo	11; 698 [RCT]	“Intraoperative MMC reduces the risk of surgical failure in eyes that have undergone no previous surgery and in eyes at high risk of failure. Compared to placebo it reduces mean intraocular pressure at 12 months in all groups of participants in this review. Apart from an increase in cataract formation following MMC, there was insufficient power to detect any increase in other serious side effects such as endophthalmitis.”
Laser interventions
Toth 2019 [30801132] Endoscopic cyclophotocoagulation (ECP) for open angle glaucoma and primary angle closure	“To evaluate the efficacy and safety of ECP in people with open angle glaucoma (OAG) and primary angle closure whose condition is inadequately controlled with drops.”	Open angle glaucoma, primary angle closure glaucoma	Endoscopic cyclophotocoagulation (ECP)	0; 0 [NA]	“There is currently no high-quality evidence for the effects of ECP for OAG and primary angle closure. Properly designed RCTs are needed to assess the medium and long-term efficacy and safety of this technique.”
Chen 2019 [30852841] Cyclodestructive procedures for refractory glaucoma	“To assess the relative effectiveness and safety of cyclodestructive procedures compared with other procedures in people with refractory glaucoma of any type and to assess the relative effectiveness and safety of individual cyclodestructive procedures compared with each other.”	Refractory glaucoma	Cyclodestructive procedures; aqueous shunts; any laser treatments	5; 326 [RCT, CCT]	“Evidence from five studies included in this review was inconclusive as to whether cyclodestructive procedures for refractory glaucoma result in better outcomes and fewer complications than other glaucoma treatments, and whether one type of cyclodestructive procedure is better than another. The most commonly reported adverse events across all five studies were hypotony and phthisis bulbi.”
Michelessi 2018 [29694684] Cyclodestructive procedures for non-refractory glaucoma	“To assess the effectiveness and safety of cyclodestructive procedures for the management of non-refractory glaucoma (i.e., glaucoma in an eye that has not undergone incisional glaucoma surgery). We also aimed to compare the effect of different routes of administration, laser delivery instruments, and parameters of cyclophotocoagulation with respect to intraocular pressure (IOP) control, visual acuity, pain control, and adverse events.”	Non-refractory glaucoma (eye that has not undergone incisional glaucoma surgery)	High energy cyclophotocoagulation (CPC); low energy CPC	1; 92 [RCT]	“There is insufficient evidence to evaluate the relative effectiveness and safety of cyclodestructive procedures for the primary procedural management of non-refractory glaucoma. Results from the one included trial did not compare cyclophotocoagulation to other procedural interventions and yielded uncertainty about any different in outcomes when comparing low-energy versus high-energy diode transscleral cyclophotocoagulation (TSCPC). Overall, the effect of laser treatment on IOP control was modest and the number of eyes experiencing vision loss was limited. More research is needed specific to the management of non-refractory glaucoma.”
Le 2018 [29897635] Iridotomy to slow progression of visual field loss in angle closure glaucoma	“To assess the effects of iridotomy compared with no iridotomy for primary angle-closure glaucoma, primary angle closure, and primary angle-closure suspects.”	Primary angle closure glaucoma	Laser peripheral iridotomy; no laser peripheral iridotomy	2; 1251 [RCT, CCT]	“The available studies that directly compared iridotomy to no iridotomy have not yet published full trial reports. At present, we cannot draw reliable conclusions based on randomized controlled trials as to whether iridotomy slows progression of visual field loss at one year compared to no iridotomy. Full publication of the results from the studies may clarify the benefits of iridotomy.”
Zhang 2017 [28231380] Perioperative medications for preventing temporarily increased intraocular pressure after laser trabeculoplasty	“To assess the effectiveness of medications administered perioperatively to prevent temporarily increased intraocular pressure (IOP) after laser trabeculoplasty (LTP) in people with open-angle glaucoma (OAG).”	Open angle glaucoma	Brimonidine; apraclonidine; acetazolamide; pilocarpine; latanoprost; apraclonidine or brimonidine given before laser trabeculoplasty; apraclonidine or brimonidine given after laser trabeculoplasty; placebo	22; 2112 [RCT]	“Perioperative medications are superior to no medication or placebo to prevent IOP spikes during the first two hours and up to 24 hours after LTP, but some medications can cause temporary conjunctival blanching, a short-term cosmetic effect. Overall, perioperative treatment was well tolerated and safe. Alpha-2 agonists are useful in helping to prevent IOP increases after LTP, but it is unclear whether one medication in this class of drugs is better than another. There was no notable difference between apraclonidine and pilocarpine in the outcomes we were able to assess.”
Michelessi 2016 [26871761] Peripheral iridotomy for pigmentary glaucoma	“To assess the effects of peripheral laser iridotomy compared with other interventions, including medication, trabeculoplasty, and trabeculectomy, or no treatment, for pigment dispersion syndrome and pigmentary glaucoma.”	Open angle glaucoma, ocular hypertension	Iridotomy with laser; combination antihypertensive medication; placebo	5; 210 [RCT]	“We found insufficient evidence of high quality on the effectiveness of peripheral iridotomy for pigmentary glaucoma or pigment dispersion syndrome. Although adverse events associated with peripheral iridotomy may be minimal, the long-term effects on visual function and other patient-important outcomes have not been established. Future research on this topic should focus on outcomes that are important to patients and the optimal timing of treatment in the disease process (eg, pigment dispersion syndrome with normal IOP, pigment dispersion syndrome with established ocular hypertension, pigmentary glaucoma).”
Li 2015 [26286384] Meta-analysis of selective laser trabeculoplasty versus topical medication in the treatment of open-angle glaucoma	“[To perform] meta-analysis of selective laser trabeculoplasty versus topical medication in the treatment of open-angle glaucoma.”	Open angle glaucoma, ocular hypertension	Selective laser trabeculoplasty; medical treatment	5; 366 [RCT, CCT]	“Both selective laser trabeculoplasty and topical medication demonstrate similar success rates and effectiveness in lowering intraocular pressure in patients with open-angle glaucoma.”
Wong 2015 [25113610] Systematic review and meta-analysis on the efficacy of selective laser trabeculoplasty in open-angle glaucoma	“[To] summarize available evidence for considering selective laser trabeculoplasty as an alternative treatment in open-angle glaucoma through systematic review and meta-analysis.”	Open angle glaucoma	Selective laser trabeculoplasty (SLT); argon laser trabeculoplasty (ALT)	10; NR [RCT]	“Meta-analysis of randomized, controlled trials shows that selective laser trabeculoplasty is non-inferior to argon laser trabeculoplasty and medication in intraocular pressure reduction and also in achieving treatment success. Number of medications reduction is similar between selective laser trabeculoplasty and argon laser trabeculoplasty. More robust evidence is needed to determine its efficacy as a repeated procedure.”
McAlinden 2014 [24310236] Selective laser trabeculoplasty (SLT) vs other treatment modalities for glaucoma	“To compare selective laser trabeculoplasty to other glaucoma treatment options in terms of their intraocular pressure lowering effect.”	Non-specific glaucoma	90º selective laser trabeculoplasty (SLT); 180º SLT; 360º SLT; 90º argon laser trabeculoplasty (ALT); 180º ALT; 360º ALT; excimer laser trabeculotomy (ELT); medical therapy	17; NR [RCT]	“In terms of the intraocular pressure lowering effect, there is no difference between selective laser trabeculoplasty and argon laser trabeculoplasty.”
Ng 2012 [22336823] Laser peripheral iridoplasty for angle-closure.	“To assess the effectiveness of laser peripheral iridoplasty in the treatment of narrow angles (i.e. primary angle-closure suspect), primary angle-closure (PAC) or primary angle-closure glaucoma (PACG) in non-acute situations when compared with any other intervention.”	Primary angle closure glaucoma, narrow angles (primary angle-closure suspect), primary angle-closure	Laser peripheral iridotomy with adjunctive laser peripheral iridoplasty; laser peripheral iridotomy alone; laser peripheral iridoplasty; any intervention to treat angle closure	1; 158 [RCT]	“There is currently no strong evidence for laser peripheral iridoplasty’s use in treating angle-closure.”
Rolim 2007 [17943806] Laser trabeculoplasty for open angle glaucoma.	“To study the effects of laser trabeculoplasty for Open Angle Glaucoma (OAG).”	Open angle glaucoma	Laser trabeculoplasty and topical beta-blocker; laser trabeculoplasty (diode laser, Nd:Yag laser); argon laser trabeculoplasty (argon laser at different power levels, argon laser at 0.1 seconds, argon laser at 0.2 seconds); trabeculoplasty (monochrome wavelength, bichromatic wavelength, two stage, one stage, superior, inferior); medication in newly diagnosed patients; medication in participants on maximal medical therapy	19; 2137 [RCT]	“Evidence suggests that, in people with newly diagnosed OAG, the risk of uncontrolled intraocular pressure (IOP) is higher in people treated with medication used before the 1990s when compared to laser trabeculoplasty at two years follow up. Trabeculoplasty is less effective than trabeculectomy in controlling IOP at six months and two years follow up. Different laser technology and protocol modalities were compared to the traditional laser trabeculoplasty and more evidence is necessary to determine if they are equivalent or not.”
Devices
Le 2019 [30919929] Ab interno trabecular bypass surgery with iStent for open angle glaucoma	“To assess the effectiveness and safety of ab interno trabecular bypass surgery with iStent (or iStent inject) for open-angle glaucoma in comparison to conventional medical, laser, or surgical treatment.”	Open angle glaucoma, ocular hypertension	Lens extraction with iStent; lens extraction alone; iStent; medical therapy	7; 764 [RCT]	“To assess the effectiveness and safety of ab interno trabecular bypass surgery with iStent (or iStent inject) for open-angle glaucoma in comparison to conventional medical, laser, or surgical treatment.” “There is very low-quality evidence that treatment with iStent may result in higher proportions of participants who are drop-free or achieving better IOP control, in the short, medium, or long-term.”
Foo 2019 [30999387] Aqueous shunts with mitomycin C versus aqueous shunts alone for glaucoma	“To evaluate the effectiveness and safety of mitomycin C (MMC) versus no MMC used during aqueous shunt surgery for reducing intraocular pressure (IOP) in primary and secondary glaucoma.”	Non-specific glaucoma patients undergoing surgery	Aqueous shunt with mitomycin C; aqueous shunt alone	5; 333 eyes [RCT]	“We found insufficient evidence in this review to suggest MMC provides any postoperative benefit for glaucoma patients who undergo aqueous shunt surgery.”
King 2018 [30554418] Subconjunctival draining minimally-invasive glaucoma devices for medically uncontrolled glaucoma	“To evaluate the efficacy and safety of subconjunctival draining minimally-invasive glaucoma devices in treating people with open angle glaucoma and ocular hypertension whose condition is inadequately controlled with drops.”	Open angle glaucoma, ocular hypertension	Xen gelatin ab interno implant; InnFocus Microshunt ab externo implant	0; 0 [NA]	“There is currently no high-quality evidence for the effects of subconjunctival draining minimally-invasive glaucoma devices for medically uncontrolled open angle glaucoma. Properly designed RCTs are needed to assess the medium- and long-term efficacy and safety of this technique.”
Tseng 2017 [28750481] Aqueous shunts for glaucoma	“To assess the effectiveness and safety of aqueous shunts for reducing intraocular pressure (IOP) in glaucoma compared with standard surgery, another type of aqueous shunt, or modification to the aqueous shunt procedure.”	Non-specific glaucoma	Aqueous shunts with modification; aqueous shunts without modification; trabeculectomy	27; 2099 [RCT]	“Information was insufficient to conclude whether there are differences between aqueous shunts and trabeculectomy for glaucoma treatment. While the Baerveldt implant may lower IOP more than the Ahmed implant, the evidence was of moderate-certainty and it is unclear whether the difference in IOP reduction is clinically significant. Overall, methodology and data quality among existing randomized controlled trials of aqueous shunts was heterogeneous across studies, and there are no well-justified or widely accepted generalizations about the superiority of one surgical procedure or device over another.”
Chow 2017 [28740733] A systematic review and meta-analysis of the trabectome as a solo procedure in patients with primary open-angle glaucoma	“To examine the availability of evidence for one of the earliest available minimally invasive glaucoma surgery (MIGS) procedures, the Trabectome.”	Open angle glaucoma	Trabectome; combination anti-hypotensive medication	4; NR [Cohort]	“Although, the Trabectome as a solo procedure appears to lower intraocular pressure (IOP) and reduces the number of glaucoma medications, more high-quality studies are required to make definitive conclusions.”