Micro-invasive glaucoma surgery (MIGS): a review of surgical procedures using stents

Figures & data

Table 1 Implants used during micro-invasive glaucoma surgery procedures – overview and status

Device	iStent^®	iStent^® inject	Hydrus	CyPass^®	iStent^® supra	XEN
Outflow pathway	Trabecular			Suprachoroidal		Subconjunctival
Manufacturer	Glaukos Inc., Laguna Hills, CA, USA	Glaukos Inc., Laguna Hills, CA, USA	Ivantis Inc., Irvine, CA, USA	Alcon Inc., Fort Worth, TX, USA	Glaukos Inc., Laguna Hills, CA, USA	Allergan plc, Dublin, Ireland
Mode of action	Penetration of the trabecular meshwork and insertion into Schlemm’s canal	Penetration of the trabecular meshwork and insertion into Schlemm’s canal	Intracanalicular scaffold is inserted into Schlemm’s canal to maintain patency and establish outflow	Creation of a controlled cyclodialysis with stented outflow to the suprachoroidal space	Transport of aqueous humor from the anterior chamber to the suprachoroidal space via stent	Outflow path from the anterior chamber to the subconjunctival space
Material	Heparin-coated non-ferromagnetic titanium	Heparin-coated non-ferromagnetic titanium	Nickel-titanium alloy (nitinol)	Polyamide	Polyethersulfone and titanium	Collagen-derived porcine gelatin cross-linked with glutaraldehyde
Size	Length: 0.3 mm in height and 1 mm in length	Length: 360 μm Diameter: 230 μm	Length: 8 mm	Length: 6.35 mm Outer diameter: 510 μm	Length: 4 mm Lumen: 0.16–0.17 mm	Length: 6 mm; Lumen: 45 μm
Specifics	Pre-loaded injector	Pre-loaded injector with two devices	Shape memory function	Lumen: 0.3 mm Stent must be loaded on injector by surgeon	Pre-loaded injector	Pre-loaded injector; 45 μm lumen size commercially available
Status	CE-mark granted in 2004: FDA approved since 2012	CE-mark granted in 2010	FDA approval for Phase IV clinical trials; CE-mark in Europe	CE-mark granted in 2008; FDA approval 2016	CE-mark granted in 2010: under FDA review	CE-mark granted 2013; FDA approved for refractory glaucoma where previous surgical treatment has failed and patient is unresponsive to maximum tolerated medical therapy; in 2016

Abbreviation: FDA, US Food and Drug Administration.

Figure 1 iStent^® and iStent^® inject.

Notes: The first generation iStent (A) has a self-trephining tip which is inserted into Schlemm’s canal. The device is maintained by the three retention arches. The lumen is directed toward the anterior chamber. (B) iStent inject possesses four side holes opening toward Schlemm’s canal. The central lumen is directed toward the anterior chamber.
Abbreviation: AH, aqueous humour.

Figure 2 Development of mean IOP after the implantation of iStent^® during combined procedures (implantation with phacoemulsification and IOL implantation).

Notes: Reduction of mean intraocular pressure compared to medicated and/or unmedicated baseline visit. In the study of Belovay et al³⁵ the results were reported separately for patients with the implantation of two or three iStents (*one iStent, **two iStents implanted). In the study by Patel et al³³ no standard deviations were given. Numbers on the horizontal axis indicate the month of visit.
Abbreviations: IOP, intraocular pressure; IOL, intraocular lens; BM, medicated baseline IOP; BU, unmedicated baseline IOP; U, unmedicated; M, medicated.

Figure 3 Development of mean IOP after the implantation of iStent^® during stand alone procedures.

Notes: Reduction of mean intraocular pressure at last visit compared to medicated and/or unmedicated baseline visit. In the study of Katz et al³⁶ the results were reported separately for patients with the implantation of one, two or three iStents. In the study of Ahmed et al³⁹ IOP lowering medication (travoprost) was re-established at month 13. Month 18 represents the IOP data including travoprost as a medical therapy. Numbers on the horizontal axis indicate the month of visit.
Abbreviations: IOP, intraocular pressure; BM, medicated baseline IOP; BU, unmedicated baseline IOP; U, unmedicated; M, medicated.

Table 2 iStent^® and iStent^® inject – overview of published study results

Authors	Study design	Eyes at baseline (n)	Diagnoses	Procedure (number of stents)	Follow-up in months	Mean IOP at baseline (mmHg) medicated (M) or unmedicated (U)	Decrease of mean IOP mmHg (%) [month]	Reduction of number of medications (mean) [month]	Wash-out phase for medication	Study details/remarks
iStent
iStent + CE (combined procedure)
Fea^Citation28	R	36	POAG	iStent (1) + CE	15	17.9 (M)	3.2 (17.3) [15]	1.6 [15]	Yes	Primary efficacy outcome: IOP. Secondary outcome measure: Number and type of glaucoma medications
Samuelson et al^Citation29	R	233	POAG; PG; PEX	iStent (1) + CE	12	18.4 (M); 25.4 (U)	8.4 (33.0) [12]	1.4 [12]	Yes	Primary efficacy endpoint: % subjects with IOP ≤21 mmHg
Craven et al^Citation30	R	240	POAG; PG; PEX	iStent (1) + CE	24	18.6 (M); 25.4 (U)	8.4 (33.1) [12] 8.5 (33.5) [24]	1.4 [12] 1.3 [24]	Yes	Primary efficacy endpoint: % subjects with IOP ≤21 mmHg at month 12. Secondary efficacy endpoint: % subjects with IOP reduction ≥20% without medication at month 12
Arriola-Villalobos et al^Citation31	NR	19	POAG; PEX; PG	iStent (l) + CE	60	19.42 (M)	3.34 (17.2) [60]	1.15 [12]; 1.0 [24]; 0.76 [36]; 0.82 [48]; 0.17 [60]	No	Primary efficacy outcome: IOP. Secondary outcome measure: Number and type of glaucoma medications
Neuhann^Citation32	NR	62	OAG; OH	iStent (1) + CE	36	24.1 (M)	9.3 (38.6) [12] 9.6 (39.8) [24] 9.2 (38.2) [36]	1.3 [12]; 1.6 [24]; 1.5 [36]	No	Efficacy outcome measures: IOP and number of glaucoma medications
Patel et al^Citation33	NR	44	POAG; PEX; other	iStent (1) + CE (n=40); iStent only (n=4)	6	21.5 (M)	5.0 (23.3) [6]	1.71 [12]	No	Efficacy outcome measures: IOP and number of glaucoma medications
Fernández-Barrientos et al^Citation34	R	33	POAG; OH	iStent (2) + CE	12	24.2 (U)	8.6 (35.5) [6] 6.6 (27.3) [12]	1.1 [12]	Yes	Efficacy outcome measures: IOP and number of glaucoma medications; Aqueous flow rate, trabecular outflow facility
Belovay et al^Citation35	NR	53	POAG; PEX; other	iStent (2 or 3) + CE	12	Two-stent: 17.3 (M) Three-stent: 18.6 (M)	Two-stent: 3.5 (20.2%) [12] Three-stent: 3.8 (20.4) [12]	Two-stent: 1.8 Three-stent: 2.2	No	Efficacy outcome measures: IOP and number of glaucoma medications
Ferguson et al^Citation39	CS	350	OAG (mild to moderate)	iStent (1) + CE	24	19.13 (M)	3.54 (18.5) [12] 3.96 (20.7) [24]	0.61 [12] 0.58 [24]	No	Primary efficacy endpoint: Development of IOP. Secondary endpoint: Number and type of ocular hypotensive medications
Seibold et al^Citation40	CS	64	POAG; other	iStent (1) + CE	12	14.7 (M)	1.5 (10.2) [12]	0.4 [12]	No	Efficacy outcome measures: IOP and number of glaucoma medications, success and failure
iStent (stand-alone procedure)
Katz et al^Citation36	R	119	OAG including; PEX and PG	iStent (1–3) (1): n=38; (2): n=41; (3): n=40	18	One-stent: 19.8 (M); 25.0 (U) Two-stent: 20.1 (M); 25.0 (U) Three-stent: 20.4 (M); 25.1 (U)	10.1 (40.4) [12–13]; 11.4 (45.6) [12–13]; 12.4 (49.4) [12–13]	Decrease of mean IOP shown for patients without medication at month 18	Yes	Primary efficacy endpoint: % subjects with IOP reduction ≥20% without medication at month 12. Secondary efficacy endpoints: % subjects with IOP ≤18 mmHg Further additional efficacy measure: mean IOP and mean IOP reduction
Ahmed et al^Citation37	NR	^Citation39	OAG	iStent (2)	18	22.2 (M); 25.3 (U)	8.2 (32.4) [13]	1.0	Yes	Pnmary efficacy endpoint: % subjects with IOP reduction ≥20% with reduction of one medication at month 12. Secondary efficacy endpoint: % subjects with IOP reduction ≤18 mmHg with reduction of one medication at month 12
Donnenfeld et al^Citation38	NR	76	OAG including; PEX and PG	iStent (2)	36	20.6 (M); 24.1 (U)	10.6 (44.0) [12] 10.6 (44.0) [24] 8.9 (36.9) [36]	35/39 eyes (89.7%) did not require ocular hypotensive medications	Yes	Primary efficacy endpoint: Month 12 IOP reduction ≥20% without medication. Secondary efficacy endpoint: Month 12 IOP reduction ≤18 mmHg
iStent inject
Voskanyan et al^Citation17	NR	99	POAG; PG; PEX	iStent inject (2)	12	26.3 (U) 22.1 (M)	10.6 (40.3) [12] 6.4 (29.0) [12]	No medication: 71.7% [12]; 15.2% with reduction on one medication [12]; 53.5% with reduction on two medications [12]; 17.2% with reduction on three medications [12]; 1%	Yes	Primary efficacy endpoint: Month 12 IOP ≤18 mmHg without medication; Secondary efficacy endpoint: Month 12 IOP ≤18 mmHg regardless of medications
Klamann et al^Citation41	CS	35	POAG; PEX; PG	iStent inject (2)	6	POAG: 21.19 (M); PEX: 23.75 (M)	POAG: 7.0 (33.0) [6]; PEX: 8.42 (35.5) [6]	POAG: 1.31; PEX: 1.29	No	Primary efficacy endpoint: % decrease from medicated baseline IOP at month 6 in subgroups of patients with POAG, PEX and PG
Fea et al^Citation42	R	94	OAG	iStent inject (2) versus FC PGA/TIM	12	iStent inject arm: 21.1 (M) 25.2 (U) Two medication arm: 20.7 (M) 24.8 (U)	iStent inject arm: 12.2 (48.4) [12] Two medication arm: 11.6 (53.2) [12]	Four patients on medication at month 12 in iStent inject arm	Yes	Patients enrolled uncontrolled on one medication Primary efficacy endpoint: % subjects with IOP reduction ≥20% without medication. Secondary efficacy endpoints: % subjects with IOP ≤18 mmHg; mean IOP and mean IOP reduction

Notes: Numbers in square brackets indicate months of follow-up. iStent, iStent inject – Glaukos Inc., Laguna Hills, CA, USA.

Abbreviations: IOP, intraocular pressure; OAG, open-angle glaucoma; POAG, primary open-angle glaucoma; PG, pigmentary glaucoma; PEX, exfoliative glaucoma; OH, ocular hypertension; R, randomized study; NR, non-randomized study; CS, case series; CE, cataract extraction; FC PGA/TIM, fixed combination prostaglandin-analog/timolol.

Table 3 iStent^® and iStent^® inject: proportion of patients achieving target IOP levels of ≤18 mmHg or ≤21 mmHg and/or an IOP reduction of ≥20% versus baseline IOP levels

Authors	Number of iStents implanted	% subjects with IOP ≤18 mmHg or ≤21 mmHg without ocular hypertensive medication	P-value or 95% CI	% subjects with IOP reduction ≥20% without ocular hypertensive medication	P-value or 95% CI
iStent
iStent + CE (combined procedure)
Samuelson et al^Citation29	1	≤21 mmHg: iStent + CE: 72% [12] ≤21 mmHg: CE alone: 50% [12]	P<0.001	iStent + CE: 66% [12] CE: 48% [12]	P=0.003
Craven et al^Citation30	1	≤21 mmHg: iStent + CE: 71% [24] ≤21 mmHg: CE: 61% [24]	P=0.036	iStent + CE: 61% [24] CE: 54% [24]	P=0.090
Arriola-Villalobos et al^Citation31	1	≤21 mmHg: iStent + CE: 42.1% [60]* ≤21 mmHg: iStent + CE: 89.5% [60]**	na	na	na
Ferguson et al^Citation39	1	≤18 mmHg: iStent + CE: 52.0% [24]	na	na	na
Seibold et al^Citation40	1	na	na	iStent + CE: 76.1% [12]	62.4%–90.0%
iStent (stand-alone procedure)
Katz et al^Citation36	1	≤18 mmHg: 89.2% [12]	74.6%–97.0%	89.2% [12]	74.6%–97.0%
	2	≤18 mmHg: 90.2% [12]	76.9%–97.3%	90.2% [12]	76.9%–97.3%
	3	≤18 mmHg: 92.1% [12]	78.6%–98.3%	92.1% [12]	78.6%–98.3%
Ahmed et al^Citation37	2	≤18 mmHg: 100.0% [12]***	na	100.0% [12]*	na
Donnenfeld et al^Citation38	2	≤18 mmHg: 92.3% [12]	79.1%–98.4%	92.3% [12]	79.1%–98.4%
		≤18 mmHg: 89.7% [36]	72.6%–97.8%	86.2% [36]	68.3%–96.1%
iStent inject
Voskanyan et al^Citation17	2	≤18 mmHg: 66.0% [12]*	55%–76%	72% [12]	61%–81%
		≤18 mmHg: 81.0% [12]**	71%–88%	93% [12]	86%–97%
Fea et al^Citation42	2	iStent: ≤18 mmHg: 92.6%[12]	85.3%–97.0%	iStent: 94.7%[12]	88.0%–98.3%
		PGA/TIM: ≤18 mmHg: 89.7%[12]	82.0%–95.0%	PGA/TIM: 91.8[12]	84.5%–96.4%

Notes: iStent, iStent inject – Glaukos Inc., Laguna Hills, CA, USA. Numbers in square brackets indicate months of follow-up. In the studies of Arriola-Villalobos et al³¹ and Voskanyan et al¹⁷ the proportion of patients with IOP values of ≤18 mmHg is given separately at final visit for 38 patients regardless of patients medication:

* without medication,

** all patients, irrespective of medication at final visit.

*** In the study of Ahmed et al³⁷ the proportion of subjects with a maximum of one medication at final visit is shown.

Abbreviations: IOP, intraocular pressure; CE, cataract extraction; PGA/TIM, fixed combination prostaglandin-analog/timolol; na., not available.

Figure 4 Development of mean IOP after the implantation of iStent inject^® during stand alone procedures.

Notes: Reduction of mean intraocular pressure at last visit compared to medicated and/or unmedicated baseline visit. iStent inject was implanted in all studies as a stand-alone procedure. In the study of Klamann et al⁴¹ the results were reported separately for patients with POAG and PEX. Numbers on the horizontal axis indicate the month of visit.
Abbreviations: IOP, intraocular pressure; POAG, primary open-angle glaucoma; PEX, exfoliative glaucoma; BM, medicated baseline IOP; BU, unmedicated baseline IOP; U, unmedicated; M, medicated.

Figure 5 The Hydrus^® micro-stent.

Figure 6 The CyPass^® micro-stent placed on a guidewire.

Figure 7 Mean IOP ± SD at baseline and 12 months after the implantation of CyPass.

Notes: In the studies of Hoeh et al¹⁹ and Vold et al⁴⁴ the implantation of CyPass was performed as a combined procedure during a cataract extraction with phacoemulsification and the implantation of an intraocular lens. In the study of García-Feijoo et al⁴³ CyPass was implanted in a stand-alone procedure in phakic and pseudophakic eyes. Numbers on horizontal axis indicate the month of visit.
Abbreviations: IOP, intraocular pressure; BM, medicated baseline IOP; BU, unmedicated baseline IOP; M, medicated; U, unmedicated.

Table 4 Implants used during micro-invasive glaucoma surgery procedures – summary of mode of action, possible risks, and potential use

Outflow pathway	Trabecular			Suprachoroidal	Subconjunctival
Devices	iStent^®	iStent^® inject	Hydrus	CyPass^®	XEN
Mode of action	Improvement of aqueous humor outflow into Schlemm’s canal			Creation of an artificial outflow for the aqueous humor into the suprachoroidal space	Formation of an artificial aqueous humor outflow path to the subconjunctival space
Possible risks	• Lower risk for hypotony • Peripheral anterior synechiae (Hydrus)			• Higher risk for (transient) hypotony • (Transient) hyphema	• Higher risk for (transient) hypotony • Bleb formation and use of MMC • Subconjunctival hemorrhage
Potential use	• Mild to moderate glaucoma • Patients with lower baseline IOP levels • Patients with multiple glaucoma medications, intolerance to glaucoma medications, and/or adherence issues			• Mild to moderate glaucoma • Patients with higher baseline IOP levels	• More severe/advanced glaucoma • Patients with higher baseline IOP levels • Need for lower target IOP levels • Patients in whom target IOP is not achieved by trabecular stents

Notes: iStent, iStent inject – Glaukos Inc., Laguna Hills, CA, USA; Hydrus – Ivantis Inc., Irvine, CA, USA; CyPass – Alcon Inc., Fort Worth, TX, USA; XEN – Allergan plc, Dublin, Ireland.

Abbreviations: IOP, intraocular pressure; MMC, mitomycin C.

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