Minimally Invasive Glaucoma Surgery: Is It Here to Stay?

ABSTRACT

The advent of minimally invasive glaucoma surgery (MIGS) has expanded the treatment options available for glaucoma by providing options for reducing intraocular pressure without the serious complication profile associated with incisional glaucoma surgery. MIGS devices aim to enhance aqueous outflow through the trabecular pathway or to bypass this pathway with drainage of fluid into the suprachoroidal or subconjunctival spaces. Having a wide range of glaucoma treatment options available helps tailor treatment to patients' individual intraocular pressure targets and aetiologies of glaucoma. This review will describe the categories and mechanisms of MIGS, comment on their relative efficacies, safety data, advantages and limitations and explore potential future changes in the glaucoma treatment paradigm in relation to MIGS.

1. Introduction

Despite the rapid advances in diagnostic and treatment modalities and the deepening understanding of the molecular mechanisms underlying ophthalmic diseases in recent decades, glaucoma remains the leading cause of irreversible blindness worldwide. Seventy‐six million individuals are estimated to be affected and its prevalence is expected to increase to exceed 111 million cases by 2040 [1]. Patients are typically asymptomatic in the early stages of disease and may present only when advanced field loss has already occurred [2]. Key goals in glaucoma management are to slow the rate of visual decline while minimising treatment side effects in order to optimise quality of life. Patients' current disease state and estimated rate of progression are considered when formulating treatment plans.

The only established way of slowing glaucoma progression is by lowering intraocular pressure (IOP). This can be achieved through medications, laser procedures and surgery. Medications, whilst generally safer, have the disadvantages of common local and systemic side effects, expense and patient challenges with drop administration and adherence [3]. Laser treatment has been demonstrated to be safe, effective and economical; however, it is not accessible to all patients due to the expense of the laser systems. Incisional surgical procedures including trabeculectomies and glaucoma drainage device surgery are generally reserved for advanced disease due to their serious potential complication profiles. These risks include blebitis and endophthalmitis, hypotony, choroidal effusions, exposure with tubes and diplopia [4].

There is a gap in the treatment algorithm for glaucoma patients with mild to moderate disease, who have already trialled maximal tolerated medical therapy and in whom laser has been ineffective or is otherwise not suitable. The risk of vision loss from glaucoma progression for patients with mild disease may not justify the risks and potential surgical morbidity of undertaking incisional glaucoma surgery [5].

Minimally invasive glaucoma surgery (MIGS) has been developed in response to this gap in the treatment paradigm and refers to a varied group of surgical techniques which aim to lower IOP while minimising disruption to the conjunctiva and sclera [6]. Potential advantages of MIGS include generally fewer postoperative visits, an improved safety profile and quicker visual rehabilitation due to less tissue disruption. While pressure reduction with MIGS is usually less than with traditional glaucoma surgery, surgical morbidity is usually also reduced, leading to their widespread uptake within the glaucoma treatment paradigm [7].

2. Overview of MIGS

2.1. Aqueous Drainage Pathways

IOP is determined by the balance between production of aqueous by the ciliary body and drainage via the trabecular and uveoscleral pathways. Within the trabecular pathway, aqueous fluid drains through the trabecular meshwork and Schlemm's canal to reach the episcleral veins; the juxtacanalicular part of the trabecular meshwork is the major element of outflow resistance within this pathway [8]. Within the uveoscleral pathway, the aqueous flows into the suprachoroidal space through the ciliary muscle due to the pressure gradient between the anterior chamber and suprachoroidal space [9]. Flow through this pathway decreases with age [10]. MIGS devices aim to enhance either these existing trabecular and uveoscleral pathways, or create an alternate pathway of aqueous flow from the anterior chamber into a subconjunctival bleb. MIGS devices are therefore divided by their site of action into (1) Schlemm's canal devices, (2) suprachoroidal devices and (3) subconjunctival devices (Figure 1).

FIGURE 1.

MIGS devices categorised by site of action.

Of note, the definitions of what constitutes a MIGS device can be varied. While the Food and Drug Administration (FDA) defines MIGS as ‘devices which enhance outflow with minimal conjunctival or scleral dissection’, the European Glaucoma Society Guidelines in their definition of MIGS specifically exclude bleb‐forming procedures and/or devices requiring conjunctival dissection for implantation (i.e., performed via an external or ‘ab externo’ approach) [6, 11]. The term ‘Minimally Invasive Bleb‐forming Surgery’ (MIBS) has been coined to describe this group of devices that form blebs [12].

3. Types of MIGS Devices (Table 1)

TABLE 1.

Categories of MIGS [13, 14, 15].

	Mechanism	Dimensions	Approval status	MRI safety
Schlemm's canal—Trabecular meshwork bypass
iStent (Glaukos Corporation)	Trabecular bypass	1 × 0.3 mm2	CE mark 2004, FDA approved 2012	MR‐Conditional
iStent inject (Glaukos Corporation)	Trabecular bypass	0.36 × 0.23 mm2	CE mark 2010, FDA approved 2018	MR‐Conditional
iStent W (Glaukos Corporation)	Trabecular bypass	0.36 × 0.36 mm2	CE mark, FDA approved 2020, iStent infinite FDA approved 2022	MR‐Conditional
Hydrus (Ivantis Inc.)	Trabecular bypass and canal dilatation	8 × 0.3 mm2	CE mark 2011, FDA approved 2018	MR‐Conditional
Schlemm's canal—Trabecular meshwork excision
Trabectome (NeoMedix Corporation)	Removes trabecular meshwork	(no device implanted)	CE mark 2005, FDA approved 2004	NA
Kahook Dual Blade (New World Medical)	Removes trabecular meshwork	(no device implanted)	CE mark 2016, FDA approved 2015	NA
TRAB360 (Sight Sciences)	Canal dilation and removes trabecular meshwork	(no device implanted)	CE mark 2015, FDA approved 2013	NA
OMNI Surgical System (Sight Sciences)	Removes trabecular meshwork and canal dilation	(no device implanted)	CE mark 2017, FDA approved 2017	NA
Gonioscopy‐assisted transluminal trabeculotomy (GATT)	Removes trabecular meshwork	(no device implanted)	NA	NA
Streamline Surgical system (New World Medical)	Removes trabecular meshwork and canal dilation	(no device implanted)	CE mark 2021, FDA approval 2021	NA
Schlemm's canal—Canal dilation only
Ab interno canaloplasty (ABiC) (Ellex iScience) with iTRACK or iTRACK advance	Canal dilation	(no device implanted)	CE mark 2008, FDA approval 2023	NA
Suprachoroidal space
CyPass Micro‐Stent (Alcon Laboratories Inc.)	Suprachoroidal bypass	6.4 mm × 510 μm	Withdrawn from market 2018	MR‐Safe
IStent Supra (Glaukos Corporation)	Suprachoroidal bypass	4 × 0.2 mm2	CE mark 2010
MINIject (iSTAR Medical)	Suprachoroidal bypass	5 × 1.1 × 0.6 mm3	CE mark 2021	MR‐Safe
Subconjunctival space
EX‐PRESS Glaucoma filtration device (Alcon laboratories Inc.)	Aqueous flow diversion	2.64 × 0.4 mm2	CE mark 2021, FDA approved 2002	MR‐Safe for 3‐Tesla or less
XEN Gel Stent (Allergan, inc.)	Aqueous flow diversion	6 × 0.5 mm2 45 μm lumen commercially available	CE mark 2013, FDA approved 2016
Preserflo MicroShunt (Santen Pharmaceutical Co.)	Aqueous flow diversion	8.5 × 0.4 mm2 70 μm lumen	CE mark 2012, FDA approved 2021	MR‐Safe
Targeting ciliary processes
Endocyclodiode laser	Targets the ciliary processes		FDA approved 1991	NA

Note: MR Conditional: the device is safe for use in a specified MR environment under specific conditions.

3.1. Canal‐Based MIGS

Canal‐based MIGS devices enhance aqueous outflow through the canal of Schlemm, an existing aqueous drainage pathway. A gonioscopic view is obtained with a prism to allow insertion of the device through the trabecular meshwork via a clear corneal incision (i.e., via an internal or ‘ab interno’ approach). The nasal part of the trabecular meshwork is usually targeted due to accessibility from a temporal incision and it also has the greatest density of aqueous collection channels [16]. These procedures can be performed at the time of cataract surgery or as a stand‐alone procedure.

3.1.1. iStent

The first trabecular‐bypass device approved was the first‐generation iStent, a heparin‐coated L‐shaped device made of titanium which was placed into the trabecular meshwork via an injector device approved by the FDA in 2012 [17]. Since then, there have been three further iterations of the device. The second‐generation ‘iStent Inject’ is smaller than the original iStent; the ‘head’, which embeds through the trabecular meshwork, is conical in shape and has four side ports to allow aqueous flow into Schlemm's canal [18]. It connects via a neck/thorax to the flange which faces the anterior chamber. Two devices, rather than one device with the original iStent, are available on the preloaded injector and are intended to be placed two to three clock hours apart. Multiple stents compared to one stent have been demonstrated to enhance pressure reduction [19]; however, each iStent has been designed to drain aqueous at the same rate as the normal physiological rate of production (2.5 μL/min) [18]. The iStent Inject W was next developed, and has a larger flange (360 μm) than the iStent Inject (230 μm) to facilitate easier placement with less chance of over‐implantation [20]. The latest model is the iStent Infinite, which has 3 preloaded iStent Inject W stents and are intended to be inserted each two clock hours apart over a span of four clock hours [21].

3.1.2. Hydrus

The Hydrus device is composed of nitinol, a nickel titanium alloy, and is a curved crescent‐shaped stent with embedded windows designed to dilate and scaffold Schlemm's canal over three clock hours [22]. It is inserted with the aid of a preloaded injector and 1 mm of its length remains within the anterior chamber as an inlet [23]. Its posterior surface is open to avoid blocking flow through the collector channels in the canal of Schlemm's external wall. Its insertion has been described as more technically difficult than other Schlemm's canal‐based devices [24].

3.2. Goniotomy

Several techniques have been developed to remove a portion or all the trabecular meshwork in order to allow direct aqueous flow into Schlemm's canal. Goniotomy techniques include gonioscopy‐assisted transluminal trabeculotomy (GATT), in which a microcatheter with an illuminated tip or a suture such as 6–0 polypropylene monofilament is used to enter and tear Schlemm's canal [25].

Goniotomy can also be performed using a Kahook Dual Blade (KDB), which uses a double‐bevelled blade to incise and remove a strip of the trabecular meshwork, or via electrocautery with the Trabectome [26].

3.3. Visco‐Dilatation of Schlemm's Canal

Outflow via Schlemm's canal can similarly be targeted by dilation of the canal with an ophthalmic viscosurgical device (OVD). Ab Interno Canaloplasy (ABiC) involves the ‘iTrack’ microcatheter with an illuminated tip being passed 360° around Schlemm's canal then slowly withdrawn while an OVD is injected in order to dilate the canal [27]. The long‐term effect of viscodilation of Schlemm's canal is unclear [12]. The TRAB360 works similarly to the iTrack but also includes a 360° trabeculotomy after viscodilation. The OMNI surgical system has a similar two‐step viscodilation and trabeculotomy procedure and has replaced the TRAB 360 [28]. Streamline (New World Medical) is another MIGS procedure approved by the FDA in 2021 that performs canal viscodilation and trabeculotomy simultaneously [29].

3.4. Suprachoroidal‐Based MIGS Devices

Suprachoroidal‐based MIGS devices enhance the existing uveoscleral pathway of aqueous outflow to lower IOP. Aqueous flow through the uveoscleral pathway is relatively independent of IOP, meaning there is not a floor effect for drainage, unlike Schlemm canal‐dependent drainage devices which are limited by the floor of the episcleral venous pressure [30]. Suprachoroidal devices are inserted via an ab interno pathway across the anterior chamber. The suprachoroidal space is a potential space with a volume that varies depending on choroidal volume, so devices within it can be susceptible to obstruction [13]. Suprachoroidal devices also face difficulties with fibrosis around the devices; due to the site of implantation, antimetabolites cannot be safely applied to prevent this complication [12].

3.4.1. CyPass

The CyPass device is made of polyimide stent with fenestrations and is inserted via a guidewire into the suprachoroidal space where it is held in place via retention rings [31]. While studies have demonstrated its efficacy in reducing IOP and usage of glaucoma medications, trials including the COMPASS‐XT have demonstrated safety concerns with an unacceptably high rate of endothelial cell loss detected in patients following phacoemulsification with CyPass compared to phacoemulsification alone [32, 33]. The device was withdrawn voluntarily from the market by the manufacturer in 2018.

3.4.2. iStent SUPRA

The iStent SUPRA is made of polyethersulfone and titanium. It is slightly curved compared with the classical iStent and has retention rings to aid its retention within the suprachoroidal space [34]. It has not been made commercially available.

3.4.3. Miniject

The Miniject is composed of a specialised silicone multi‐porous material which promotes integration with tissue. It is currently the only commercially available MIGS device to target the suprachoroidal space and is accessible in Europe and Australia; it is undergoing a pivotal trial to demonstrate safety and efficacy under the FDA. It is made of the same material as the STARflo device, a pre‐existing suprachoroidal device which had not been shown to maintain efficacy in the long‐term and was never made commercially available [35].

3.5. Subconjunctival MIGS Devices

Subconjunctival MIGS devices, or MIBS, facilitate aqueous humour drainage from the anterior chamber into the subconjunctival space where it is absorbed into the subconjunctival capillaries and lymphatics; this is an artificial route as aqueous does not usually enter the subconjunctival space [36]. Much like conventional glaucoma filtration surgery, the efficacy and longevity of these devices require the off‐label use of antimetabolites to prevent conjunctival fibrosis. However, these devices minimise the number of steps in the operation and are less operator‐dependent. These devices can be used for patients who require more significant IOP reductions than other MIGS devices, including those with more moderate to severe glaucoma.

3.5.1. XEN

The XEN gel‐stent is a 6 mm tube made of porcine gelatin cross‐linked with glutaraldehyde [37]. It was designed to be inserted ab interno through an injector across the anterior chamber into the subconjunctival space to form a bleb; off‐label Mitomycin C (MMC) is used [38]. It can alternatively be inserted through an ab externo technique. The stent is hydrophilic and swells when in contact with water, holding the stent in place. The stent comes with lumens sized 45, 63 and 140 μm; however, only the XEN‐45 is commercially available. The XEN‐45 provides around 6–8 mmHg of internal resistance, decreasing the risk of hypotony [38].

3.5.2. Preserflo MicroShunt

The Preserflo MicroShunt is a flexible tube made of poly(styrene‐block‐isobutylene‐block‐styrene) (SIBS), a biocompatible material previously used in coronary stenting that incites minimal inflammation or fibrosis [39]. The device is inserted via an ab externo technique involving a conjunctival incision and construction of a scleral pocket into which the two wings of the device sit to help prevent tube migration and minimise peri‐tubular leak. Enhanced efficacy was found with the use of the 0.04% rather than the 0.02% concentration of mitomycin C [40].

3.5.3. EX‐PRESS

The EX‐PRESS glaucoma filtration device is a stainless‐steel device with either a 50 μm lumen or a 200 μm lumen that is inserted under a partial‐thickness scleral flap to drain fluid from the anterior chamber into the subconjunctival space [41]. The smaller lumen device can be chosen for patients with a higher risk of hypotony. Similar to a trabeculectomy, the partial thickness scleral flap is tied with sutures titrated to adjust flow. The pressure reduction seen with the EX‐PRESS is similar to a trabeculectomy; however, fewer complications such as hypotony and choroidal effusions are reported with the EX‐PRESS device [42]. The device is at risk of malposition or extrusion.

3.6. Laser Ablation of Ciliary Processes

3.6.1. Endoscopic Cyclophotocoagulation

Endoscopic cyclophotocoagulation (ECP) laser is performed through an ab interno approach and involves ablating ciliary processes with diode laser under endoscopic visualisation to reduce the production of aqueous humor [43]. Targeting aqueous production comes with a potential risk of long‐term hypotony, although this is generally reported to be less common than with transscleral cyclophotocoagulation [44].

3.7. Intracameral Drug‐Eluting Delivery Devices

Drug‐eluting devices have been developed to overcome treatment barriers of non‐adherence and side effects associated with topical medications. The iDose TR is a small (1.8 × 0.5 mm²) biocompatible titanium device implanted into the trabecular meshwork that continuously releases travoprost into the anterior chamber [45]. The implant has a scleral anchor portion, a body which acts as a reservoir for the drug and a membrane over which the drug is eluted. The device has been shown to be non‐inferior to topical timolol in pressure reduction at 12 months in randomised controlled trials [46]. A bimatoprost implant (Durysta), approved by the FDA in 2020, contains the drug as a biodegradable polymer to be released over a 90‐day period and is designed to rest in the inferior anterior chamber angle. The implant has demonstrated non‐inferiority to topical timolol in IOP reduction over 12 weeks in randomised studies [47, 48].

4. Clinical Outcomes and Efficacy

Devices with prospective randomised data are focussed on in the subsequent discussion. Of note, the study populations for these MIGS trials were limited to patients with hypertensive mild to moderate OAG. Studies either assessed washed‐out IOP reduction (ocular hypotensive medications ceased prior to, or at the time of, surgery) (Table 2) or IOP reduction without medication washout (Table 3).

TABLE 2.

Randomised studies without preoperative washout.

	Groups (n)	Follow up	Starting IOP (mmHg)	IOP mean reduction (mmHg)	Percentage reduction	Medicine reduction
Fea, 2010 [49]	iStent +CE/IOL (12) CE/IOL (24)	15 months	17.9 ± 2.6 17.3 ± 3.0	3.2 ± 3.0 1.6 ± 3.2	17.3% 9.2%	1.6 (80%) 0.6 (32%)
Samuelson, 2011 (US iStent study) [17]	iStent/CE/IOL (117) CE/IOL (110)	1 year	18.7 ± 3.3 18.0 ± 3.0	1.5 ± 3.0 1.0 ± 3.3	8% 5.5%	1.4 ± 0.8 (87%) 1.0 ± 0.8 (73%)
Craven, 2012 (US iStent study) [50]	iStent+CE/IOL (116) CE/IOL (117)	1 year 2 years	18.6 ± 3.4 17.9 ± 3.0 17.1 ± 2.9 17.8 ± 3.3	1.6 0.9 1.5 0.9	8.6% 5.0% 8.1% 0.6%	1.4 (88%) 1.1 (73%) 1.3 (81%) 1.1 (73%)
Pfeiffer, 2015 (Hydrus II study) [51]	Hydrus+CE/IOL (50) CE/IOL (50)	2 years	18.9 ± 3.3 18.6 ± 3.8			1.5 (75%) 1.0 (50%)
Falkenberry, 2020 [52]	KDB + CE/IOL iStent+CE/IOL	1 year	18.5 18.5	3.1 2.4	15% 11.4%	1.0 (79%) 1.0 (71%)
Jones, 2019 (US cohort HORIZON) [53]	Hydrus+CE/IOL (219) CE/IOL (112)	2 years	18.3 ± 3.4 16.9 ± 3.5			1.2 (75%) 0.8 (59%)
Samuelson, 2019 (HORIZON International) [54]	Hydrus+CE/IOL (369) CE/IOL (187)	2 years	17.9 ± 3.1 18.1 ± 3.1	1.1 0.7	6.1% 3.9%	1.4 (82%) 1.0 (59%)
Samuelson, 2019 (iStent inject) [18]	iStent inject+CE/IOL (387) CE/IOL (118)	2 years	17.5 ± 3 17.5 ± 2.8			1.2 (75%) 0.8 (53%)
Ahmed 2022 (Horizon international) [55]	Hydrus+CE/IOL (308) CE/IOL (134)	5 years	17.9 ± 3.1 18.1 ± 3.1	1.1 0.9	6.1% 5%	1.2 (71%) 0.8 (47%)
Fan Gaskin 2024 [56]	iStent Inject (56) CE/IOL (48)	2 years	17.7 ± 4.0 17.1 ± 3.1	2.3 1.5	13% 9%	1 (59%) 0.3 (17%)
Panarelli, 2024 [57]	Preserflo (395) Trabeculectomy (132)	2 years	21.1 ± 4.9 21.1 ± 5.0	7.2 10.4	34% 49%	2.2 (71%) 2.5 (86%)

Abbreviations: CE, cataract extraction; IOL, intraocular lens; IOP, intraocular pressure.

TABLE 3.

Randomised studies with preoperative/postoperative washout.

	Groups (n)	Follow up	Starting IOP (mmHg)	IOP mean reduction (mmHg)	Percentage reduction
Samuelson, 2019 (iStent inject) [18]	iStent inject+CE/IOL (387) CE/IOL (118)	2 years	24.8 ± 3.3 24.5 ± 3.1	7.0 ± 4.0 5.4 ± 3.7	31.1% 27.3%
Pfeiffer, 2015 (HYDRUS II Study) [51]	Hydrus+CE/IOL (50) CE/IOL (50)	1 year 2 years	26.3 ± 4.4 26.6 ± 4.2	9.7 9.2 9.4 7.4	36.9% 34.6% 36.5% 27.8%
Jones, 2019 (US cohort of Horizon) [53]	Hydrus+CE/IOL (219) CE/IOL (112)	2 years	25.6 ± 3.2 25.3 ± 2.9	8.1 6	31.6% 23.7%
Samuelson, 2019 (HORIZON international) [54]	Hydrus+CE/IOL (369) CE/IOL (187)	1 year 2 years	25.5 ± 3.0 25.4 ± 2.9	8.5 6.3 7.6 ± 4.1 5.3 ± 3.9	33.3% 24.8% 29.8% 20.9%

Abbreviations: CE, cataract extraction; IOL, intraocular lens; IOP, intraocular pressure.

4.1. iStent

Data for the iStent (first generation) comes from the randomised controlled trial (RCT) the ‘US iStent study’ [17]. No medication washout was performed for this cohort. Samuelson et al. reported that at 1 year, implantation of a single iStent combined with cataract surgery (n = 117) compared to cataract surgery alone (n = 110) demonstrated an 8% (1.5 ± 3) vs. a 5.5% (1.0 ± 3.3) reduction in IOP and 87% vs. 73% medication reduction [17]. The same cohort was followed up over 2 years and reported to have an ongoing IOP reduction with the combined group (8.1%, 1.5 mmHg) and only 0.6% (0.1 mmHg) with cataract surgery alone, with a similar mean medication reduction of 81% vs. 73% [50].

For iStent inject, the ‘iStent Inject Study’ authored by Samuelson et al. demonstrated an IOP reduction post‐medication wash out of 31.1% (7.0 ± 4.0 mmHg) with an iStent inject and cataract surgery (n = 387) compared to 27.3% (5.4 ± 3.7 mmHg) in the cataract surgery alone group (n = 118) at 2 years (p < 0.001) [18]. A greater proportion of patients with the iStent Inject and cataract surgery reached a > 20% unmedicated IOP reduction (75.8% vs. 61.9%, p = 0.005). The only other RCT comparing combined cataract surgery and iStent Inject (n = 56) with cataract surgery alone (n = 48) comes from Australia [56], and identified that the combined surgery group achieved fewer ocular hypotensive medications at 2 years compared to the cataract surgery alone group (0.7 ± 0.9 vs. 1.5 ± 1.9; p = 0.008); in the combined group, 57% of eyes were on no glaucoma medications compared to 36% in the cataract surgery alone group. This study did not perform pre‐surgery medication washout and did not identify a significant difference in IOP between the two groups at 2 years.

For the iStent Infinite, a prospective, single‐arm trial looking at stand‐alone implantation of iStent Infinite in patients with OAG found a mean IOP reduction at 12 months of 5.9 (± 0.6) mmHg [21].

4.2. Hydrus

The major RCTs for the Hydrus are the Hydrus II study and the HORIZON trial. The Hydrus II study, published in 2015, reported that at 1 year with a Hydrus stent and cataract surgery (n = 50) compared to cataract surgery alone (n = 50) there was a similar washed‐out pressure reduction of 36.9% vs. 34.6%. This difference had increased at 2 years, to become 36.5% (9.4 mmHg) with the Hydrus and cataract surgery and 27.8% (7.4 mmHg) with cataract surgery alone. A greater proportion of patients with the Hydrus and cataract surgery reached a > 20% unmedicated IOP reduction (80% vs. 46%, p < 0.0008) [51].

The HORIZON trial, first published in 2019, reported that at 1 year the Hydrus stent with cataract surgery (n = 369) compared to cataract surgery alone (n = 187) had a washed‐out pressure reduction of 33.3% vs. 24.8%. This difference remained significant at 2 years, with the Hydrus stent and cataract surgery group having a pressure reduction of 29.8% (7.6 ± 4.1 mmHg) vs. 20.9% (5.3 ± 4.2 mmHg) (mean difference −2.3, 95% confidence interval −3 to −1.6 mmHg). A greater proportion of patients with the Hydrus and cataract surgery reached a > 20% unmedicated IOP reduction (77.3% vs. 57.8%, p < 0.001) [54]. This was consistent with the independent reporting of the US cohort of the HORIZON trial in 2019, which demonstrated a washed‐out pressure reduction of 31.6% vs. 23.7% comparing Hydrus and cataract surgery with cataract surgery alone at 2 years [53].

Ahmed et al. published the five‐year outcomes of HORIZON in 2022 (n = 442). No medication washout was performed at this time [55]. For the Hydrus and cataract surgery group (n = 308) compared to the cataract surgery alone group (n = 134), there was only a small difference of 6.1% compared to a 5.0% in IOP reduction (not statistically significant) but a larger 70.6% compared to 47.1% medication reduction. This final medication usage in the Hydrus and cataract surgery group compared to the cataract surgery alone group was 0.5 ± 0.9 drops versus 0.9 ± 0.9 drops (p < 0.001). A post hoc analysis also demonstrated a slower rate of visual field progression in the combined group compared to cataract surgery alone (−0.26 dB/year vs. −0.49 dB/year, p = 0.01). There was further a decreased risk of future glaucoma surgery in the Hydrus and cataract surgery group (2.4%) compared with the cataract surgery group alone (6.2%, p = 0.027) [55]. There was no increased risk of adverse events; in particular, there was no difference in the corneal endothelium counts.

4.3. Miniject

In a meta‐analysis of prospective non‐randomised studies (STAR I, II, III trials) (n = 66), mean IOP reduced from 23.8 ± 3.3 with 2.4 medications to 14.4 ± 4.5 with 1.4 medications (39% reduction). An IOP reduction > 20% occurred in 89.4% of patients. Endothelial cell density decreased by 6% over the 2 years [58]. There is currently no published level 1 evidence for this device.

4.4. GATT and Non‐GATT Goniotomy

A meta‐analysis pooled 11 cohorts of patients undergoing GATT with cataract surgery (379 eyes, prospective and retrospective cohorts included); no study included compared GATT to a control arm [59]. Patients who underwent GATT had a baseline IOP of 21.8 mmHg (range 19.5 mmHg—24.1 mmHg) on 2.9 (range 2.36–3.44) medications and it reduced to 12.5 mmHg (range 10.0 mmHg‐15.0 mmHg) on 0.83 (range 0.37–1.09) medications at 1 year post‐surgery. For patients undergoing non‐GATT goniotomy such as KDB, Trabectome or Excimer Laser Trabeculostomy combined with cataract surgery, the baseline IOP was 20 mmHg (5198 eyes, 95% CI 19.2–20.8) on 2.3 medications (95% CI 2.09–2.53 medications) and reduced to 14.6 mmHg (95% CI 14.3–15.0) on 1.41 (95% CI 1.22–1.62) medications. This meta‐analysis demonstrated a greater IOP and medication reduction for GATT and non‐GATT goniotomy combined with cataract surgery compared to combined trabecular bypass procedures with cataract surgery. However, it should be noted that the goniotomy groups had higher baseline pressures with a capacity for larger potential drops, which could have confounded the results. An RCT comparing KDB combined with cataract surgery (n = 21) vs. cataract surgery alone (n = 21) with POAG demonstrated no significant difference in IOP or drop burden at 12 months [60].

4.5. Xen

In a RCT, surgical success at 12 months (defined as a > 20% IOP reduction without increasing medication, clinical hypotony or surgical intervention) was similar with a Xen (n = 95) vs. a trabeculectomy (n = 44) (62% vs. 68%, no statistical difference). IOP‐related change, however, was improved with a trabeculectomy (2.8 mmHg, p = 0.024) [61]. There were no changes in endothelial cell density noticed compared to baseline 5 years after Xen implantation [62].

A prospective study over 5 years (n = 80) found an IOP reduction of 19.6 ± 7.1 mmHg to 12.6 ± 3.1 mmHg at 5 years in the standalone Xen group (n = 16) and a reduction of 19.8 ± 7.0 mmHg to 12.6 ± 3.1 mmHg in the combined Xen and phacoemulsification group (n = 64). Medication with both groups reduced from 2.0 ± 1.3 to 0.8 ± 1.1. There was a high rate of 49% requiring needling [63].

4.6. Preserflo

There has been one RCT comparing Preserflo with MMC 0.2 mg/mL (n = 395) to trabeculectomy also with MMC 0.2 mg/mL (n = 132) [64]. Starting at a similar preoperative IOP (21.1 ± 4.9 mmHg and 21.1 ± 5.0 mmHg, respectively), the postoperative IOP was 14.3 ± 4.3 mmHg (−29%) with a Preserflo compared to 11.1 ± 4.3 mmHg (−45%) for a trabeculectomy at 1 year (−1.2 mmHg difference, 95% CI −2.3–0.09) and 13.9 ± 3.9 mmHg versus 10.7 ± 3.7 mmHg in the trabeculectomy group at 2 years. Mean medication use decreased from 3.1 and 2.9 for the Microshunt and trabeculectomy groups respectively to 0.9 and 0.4 (p < 0.001). Hypotony was more common with trabeculectomy (51% vs. 31%, p < 0.001) [57].

A meta‐analysis analysing seven studies including prospective and retrospective data for 1353 eyes suggested a mean IOP reduction for Preserflo vs. trabeculectomy of 7.82 vs. 10.4 mmHg. This represented a reduction from a mean pre‐operative IOP of 20.9 and 21.5 mmHg to a mean post‐operative IOP of 13.3 and 11.3 mmHg, respectively [39]. There was greater reduction in topical glaucoma drops with a trabeculectomy (−0.32 [−0.58, −0.07], p = 0.014). There were no differences in hypotony, choroidal effusions or flat anterior chambers between the groups; however, patients in the trabeculectomy group did have more bleb‐related complications and had higher re‐intervention rates. Another 2‐year multicentre study of 81 patients who received Preserflo reported a success rate (> 20% IOP reduction in IOP and IOP < 21 with or without medication) in years 1 and 2 of 74.1% [65]. There was a mean IOP decrease from 21.7 ± 3.4 mmHg on 2.1 medications to 14.1 ± 3.2 mmHg on 0.5 medications at 2 years. Higher success rates were seen with the 0.4 mg/mL compared to the 0.2 mg/mL MMC concentration.

The study on Preserflo with the longest follow‐up observed 23 Hispanic patients and reported a mean IOP reduction from 23.8 mmHg on 2.4 medications at baseline to 12.4 mmHg on 0.8 medication 5 years after surgery (n = 21 maintained follow‐up) [66]. Based on two studies [67, 68], the mean surgical time was 54 min for Preserflo and 73 min for a trabeculectomy, and the mean number of follow‐up visits was 9.85 for Preserflo and 14.25 visits for trabeculectomy over 18 months of follow‐up in two retrospective cohort studies [67, 68].

4.7. Comparative Trials of MIGS

A RCT called COMPARE compared the Hydrus (n = 75) to the implantation of two iStents (first generation) as stand‐alone surgery (n = 77) [23]. A greater proportion of Hydrus patients (46.6%) compared to iStent patients (24%) were medication‐free at 12 months. There was a decrease in medicated IOP found with the Hydrus group (−1.7 ± 4.0 mmHg) but not with the iStent group (−1.0 ± 4.0); however, no statistical difference was found when the two groups were compared (−0.7 mmHg, p = 0.3). The proportion that reached an unmedicated reduction of > 20% at 24 months was 40% for patients with Hydrus and cataract surgery and 13% for the iStent and cataract surgery group (p < 0.001).

A randomised trial was reported in 2020 by Falkenberry et al. comparing KDB combined with cataract surgery (n = 164) with single iStent with cataract surgery (n = 164) [52]. At 1 year, in the KDB group compared to the iStent group, there was an increased IOP reduction of 15% vs. 11.4% and medication reduction of 79% vs. 70.5%; however, these were not statistically significant.

A randomised trial compared the implantation of stand‐alone iStent (n = 38), two iStents (n = 41) and three iStents (n = 40) (generation one) and found a washed‐out IOP reduction of 7.6, 9.2 and 10.9 mmHg at 42 months [19]. A greater proportion of patients with more iStents reached a > 20% unmedicated IOP reduction at 42 months (61%, 91% and 91%, p < 0.0008).

5. Aggregated Reviews

Looking at aggregated randomised controlled trials of MIGS devices including medication washout (iStent Inject trial, the Hydrus II study and the HORIZON trial), cataract surgery alone for hypertensive open angle glaucoma patients has been reported to provide an IOP reduction of approximately 5.4 to 7.6 mmHg (equivalent around 21% to 28%) [69]. In addition to cataract surgery alone, the combination g in the iStent Inject study led to an additional 3.8% (1.6 mmHg) IOP reduction, the Hydrus in the Hydrus II study led to an additional 8.7% (2 mmHg) IOP reduction and the Hydrus in HORIZON led to a similar additional 8.9% (2.3 mmHg) IOP reduction. At 2 years, the iStent Inject group had a 1.8% lower rate of requiring surgical interventions and the Hydrus had a 1.6% lower rate compared to cataract surgery alone [69].

A meta‐analysis using random‐effects network meta‐analyses, which indirectly compare multiple interventions, suggested a greater unmedicated glaucoma control with the Hydrus compared with the iStent [70]. However, only data regarding the first‐generation iStent was available at the time of the analysis. Across the devices, there was a modest absolute medication reduction of around half a medication (iStent 0.42, Hydrus 0.41, CyPass 0.5).

6. Safety and Adverse Outcomes

The safety of MIGS devices is benchmarked against that of incisional glaucoma surgery. In the Primary Tube vs. Trabeculectomy study, there was a complication rate after 1 year of 29% for tube surgery and 41% for trabeculectomy [71]. Serious complications that resulted in a loss of two or more Snellen lines or required repeat surgery occurred in 1% of tube patients and 7% of trabeculectomy patients. In a systematic review of MIGS studies involving trabecular meshwork bypass and goniotomies, all MIGS groups had equal or fewer sight‐threatening events or further glaucoma surgery than the control (cataract surgery) [59]. Aggregating data from prospective and retrospective cohorts across the MIGS devices, the most common adverse events in MIGS groups vs. the control groups were stent obstruction (14.5% vs. 0%), inflammation (13.5% vs. 16.7%), surgical reintervention (10.7% vs. 13%) and diminished visual field (5.1% vs. 7.7%) [59].

The safety data for MIGs study is reported inconsistently between studies, with many studies not including the rate of common complications such as IOP spikes and hyphaema [59, 69]. For the iStent Inject study, there was no statistical difference in complication profiles in the group with combined surgery vs. cataract surgery alone, except for foreign body sensation, which occurred more frequently in the iStent Inject group (2.3% vs. 0%) [18]. Obstruction of the iStent inject was reported in 6% (n = 24) of eyes with the iStent inject. Although uveitis occurred more frequently in the iStent inject group, this difference was not statistically significant. There were no large hyphaemas (> 10% of the anterior chamber) reported. At 2 years, there was no difference in endothelial cell loss between the combined group and cataract surgery alone group (−13.1% vs. −12.3%). Serious complications such as hypotony, choroidal effusions, or endophthalmitis have not been reported in association with iStents [18]. Schlemm‐canal‐based devices have the advantage of negligible risk of hypotony as intraocular pressure is limited by episcleral venous pressure, generally around 7.5–9 mmHg [72].

For the Horizon study, complications were not reported in terms of statistically significant differences between the two groups [54]. Uveitis occurred more frequently in Hydrus eyes compared with cataract surgery alone (5.6% vs. 3.7%). Corneal oedema was also more frequent in the Hydrus group (1.4% vs. 0%). The Hydrus device could not be placed in 2.9% of cases (e.g., due to canal narrowing) and 1.6% of devices were not ideally placed (e.g., the inlet was > 1 mm outside of canal). Obstructive peripheral anterior synechiae (PAS) occurred in 3.8% of the Hydrus group and non‐obstructive PAS in 14.9%; however, this did not tend to affect IOP control.

KDB was more likely to have hyphaema than the iStent cataract surgery group (3.7% vs. 1.2%) [52]. Patients undergoing GATT were found to have a higher rate of hyphaema than non‐GATT goniotomies such as KDB or trabecular bypass [59]. Trabectome can be associated with a higher frequency of blood reflux and hyphaema than other goniotomy techniques [73]. There is a risk of closure from the leaflets left after goniotomy.

For the CyPass microstent, 27.2% of patients experienced endothelial cell loss greater than 30% compared to 10% of cataract surgery only eyes at 5 years in the COMPASS XT CyPass study, leading to the withdrawal of the device from the market [32]. The degree of endothelial loss was correlated with the length of the device in the anterior chamber. This difference in endothelial cell loss was not apparent at 2 years, highlighting the importance of post‐market surveillance [59]. Unsurprisingly, a meta‐analysis has suggested endothelial cell loss may be greater with implanted devices compared to techniques in which no device is left [74]. Endothelial cell loss at 5 years was greater in the Hydrus group (1.96×) and CyPass group (2.72×) compared to the iStent Inject group (1.49×), which was not significantly different from the cataract surgery alone group [75].

MIBS are vulnerable to the same complications as traditional glaucoma filtration surgeries due to the presence of the bleb, including conjunctival fibrosis, bleb leak, blebitis and bleb‐related endophthalmitis [76]. They may also produce hypotony as they do not have the floor effect inherent with Schlemm's canal‐based MIGS devices. The Xen gel stent has been reported to have a high rate of bleb encapsulation requiring post‐operative intervention (up to 50%) [63]. Bleb‐related complications such as blebitis and endophthalmitis can also occur [77].

7. Factors Involved in Device Selection

Device selection may depend on surgeon factors, such as experience and access to a particular device, and patient factors, including glaucoma severity and type, medical comorbidities including those that would increase bleeding risk and ability to follow up, as well as affordability [14]. Surgeons will often decide first if there is a visually significant cataract in a glaucoma patient and next if a concurrent MIGS operation might be suitable in that patient's circumstances; approval of stand‐alone MIGS procedures varies across different countries and health systems. Particular MIGS devices may be contra‐indicated in settings of a history of metal allergy, Schlemm's canal narrowing, bleeding tendencies and uveitis [69].

Patients with angle abnormalities such as PAS or neovascularisation of the angle are generally precluded from angle‐based surgery [78]. For patients with uveitic glaucoma, an excisional goniotomy procedure could be more suitable than leaving an implanted device that could act as a foreign body [69]. Patients with elevated episcleral pressure such as those with Sturge‐Weber syndrome, a tight scleral buckle, or Graves' disease may not be suitable for a Schlemm's canal targeting procedure.

In patients with a high‐bleeding risk, excisional goniotomy may not be suitable due to the high risk of bleeding with removing trabecular meshwork and the direct communication created between collector channels and the anterior chamber. The iStent inject, which is associated with less disruption to the trabecular meshwork and only a small passage to the collector channels, could be more appropriate. Whether patients were on anticoagulants was not reported generally in trial data [69]. It remains unclear if patients with certain subtypes of glaucoma such as pseudoexfoliation do better with one intervention compared to another [79].

8. Recent Advances and Innovations

Adoption of new devices has often been industry‐led before robust randomised control data had been available [12].

More recently, Femtosecond laser image‐guided precision trabeculotomy (FLIGHT) has been used to create pathways with a laser through the trabecular meshwork, guided by optical coherence tomography. A pilot study which was prospective and single‐armed (n = 18) demonstrated no serious adverse outcomes, patency of the channels on OCT at 24 months and a 35% mean IOP reduction [80].

9. Advantages of MIGS

MIGS devices have several advantages. MIGS devices may provide an option for patients who have not reached ideal IOP control with medications and/or laser, or who are intolerant of or non‐adherent with their topical eye drops. Compared to medical therapy, MIGS avoid the side effects from topical drops, difficulties with patient adherence and fluctuations that can occur in pressure [81]. A report on patients within the iStent Inject clinical trial demonstrated enhanced patient‐reported outcomes in patients who had received iStents compared to cataract surgery alone, likely due to not requiring drops [82]. Most MIGS devices can be performed at the time of cataract surgery, potentially reducing the number of surgeries a patient might undergo [13].

The surgical techniques compared to incisional surgery are generally described as easier, quicker and safer [12]. United Kingdom Glaucoma specialists anticipated an increase in the use of Preserflos compared to trabeculectomies for this reason [83]. Post‐operative recovery is usually quick due to the limited conjunctival and scleral dissection required for most MIGS devices. While complications such as device obstruction, malposition, hyphaema and IOP spikes can occur with MIGS devices, the complication profiles particularly of the non‐bleb forming MIGS devices are only marginally increased compared to cataract surgery and the serious complications associated with blebs, such as blebitis and hypotony, are largely avoided [24, 76].

The IOP reduction, while modest with many MIGS devices compared with incisional glaucoma surgery, may be adequate for mild to moderate glaucoma. Schlemm's canal based MIGS and suprachoroidal‐based MIGS additionally preserve the conjunctiva so future bleb‐based surgeries can be performed if required.

10. Limitations of MIGS

There are several limitations of MIGS. MIBS may disrupt the conjunctiva and decrease the success rate of a future trabeculectomy if required [12]. They also share the serious complications of trabeculectomies, including the potential for blebitis and endophthalmitis, even years after the original surgery. MIGS devices also collectively tend to have small lumens that help to prevent hypotony; however, this can also make the devices vulnerable to blockage by materials such as fibrin, haem, or lens matter.

The IOP lowering effect of MIGS tends not to be as pronounced as incisional glaucoma surgery, so MIGS may not be effective for patients who require low target intraocular pressures, such as patients with normal tension glaucoma [13]. Patients selected for most of the MIGS trials had hypertensive mild–moderate open angle glaucoma and there is limited evidence on the effectiveness of Schlemm's canal procedures in patients with a starting pressure of 21 mmHg or less (NTG), which accounts for up to half of open angle glaucoma across the world [84]. It is likely that trabecular‐based procedures are less likely to work well in patients with lower baseline pressures due to the floor effect of the episcleral venous pressure. A multi‐centre consecutive case series involving 62 eyes did suggest that iStent Inject was effective at lowering intraocular pressure in patients with normal tension glaucoma (22% reduction, 15.8 ± 3.0 mmHg to 12.3 ± 2.6 mmHg) and reducing their medication burden (by 70%) [81].

There are certain populations in which MIGS are usually not appropriate, including glaucoma with severe visual field loss, secondary glaucomas such as neovascular glaucoma or active uveitic glaucoma [13]. Angle‐based interventions may not be possible in angle closure glaucoma with persisting PAS. Suprachoroidal devices may not be as successful in patients with a history of scleritis. Patients with pseudoexfoliation and pigmentary glaucoma were not included in the HORIZON and iStent Inject trials, but were included in some other trials [18, 49, 52].

There is limited data about the long‐term effectiveness of MIGS and limited evidence about different devices comparative performances [13]. A significant number of patients are lost to follow‐up with time and there is limited data for the 5‐year effectiveness for most MIGS [59]. Patients lost to follow‐up could include patients that went on to have incisional surgery due to failure of the MIGS device.

Many MIGS devices have been implanted at the time of cataract surgery and it can be difficult to quantify the additional contribution of the MIGS device compared to cataract surgery alone [12]. Virtually all RCTs performed involving MIGS were industry‐sponsored and are at risk of industry sponsorship bias [69]. The expense of MIGS devices makes them inaccessible in most lower‐income countries [12].

11. Future Directions

The world of MIGS is a constantly evolving space. However, there is a lack of standardised randomised control trial data about MIGS with varying outcome measures used [24, 76]. Much of the literature are non‐comparative, non‐randomised studies and include varying interventions such as cataract surgery which make comparisons difficult. Many studies are retrospective, and so can be confounded by selection bias, inadequate frequency of IOP measurements and loss to follow‐up [85]. Most studies did not measure washed‐out IOP due to safety concerns. The interpretation of medicated IOP levels and medication burden pre‐ and post‐operatively can be confounded by the medication adjustments being performed at the investigators' discretion [59]. Different classes of IOP‐lowering medications have different efficacies which confound measures of mean medication reduction, a common metric cited in studies. There is limited data on long‐term data with the various MIGS, an important consideration given the results with CyPass.

Well‐designed studies are essential to establish a robust evidence base for the use of MIGS. The US FDA has recommended that RCTs cover a MIGS' efficacy, QOL outcomes and safety reports up to 24‐months [70]. The World Glaucoma Association has also published guidelines with regard to study design and reporting of outcomes; however, these guidelines have been inconsistently followed (< 50% of trials) [86].

Effectiveness outcomes would ideally use measures of function such as visual field results, as included in a RCT examining the Hydrus [55]. It is important to examine the cost‐effectiveness of MIGS for the individual patient and broader health system [70]. MIGS devices tend to be more expensive than traditional glaucoma surgery and it remains to be seen whether their cost justifies their benefits in terms of drop reduction, quality of life and clinical outcomes. A study performed by Fea et al. based on the iStent trial suggested that combined iStent and cataract surgery compared to cataract surgery was cost‐effective within the Italian National Healthcare Service [87]. There have been conflicting reports on the cost–benefit of Preserflo vs. trabeculectomy [68, 88].

12. Conclusions

There has never been such a diverse range of treatment options for the reduction of IOP in the history of ophthalmology. MIGS tends to have a better safety profile than incisional glaucoma surgery; however, this is balanced against a more modest IOP lowering effect [13]. MIGS devices tend to have a quicker recovery time, preserve tissue for further future incisional surgeries if required and can be performed at the time of cataract surgery [81]. MIGS provide a surgical option for patients with modest IOP reduction targets and/or a need to reduce medication burden, for whom incisional surgery would have too high a risk. There are limitations in the literature supporting MIGS, including heterogeneity of reporting outcomes, potential biases from industry sponsorship, restricted long‐term data on safety, and inadequate randomised control data for several of the devices. Future trials which are run in accordance with recommended reporting guidelines and consider cost‐effectiveness will be useful in expanding the evidence‐base surrounding the use of MIGS.

Conflicts of Interest

The authors declare no conflicts of interest.

Jain N. and Fan Gaskin J. C., “Minimally Invasive Glaucoma Surgery: Is It Here to Stay?,” Clinical & Experimental Ophthalmology 53, no. 8 (2025): 1025–1038, 10.1111/ceo.14571.

Data Availability Statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.