Glaucoma is a progressive optic neuropathy that can result in irreversible visual field loss and eventual blindness. It affects an estimated 64.3 million people, or 3.5% of the world’s population ages 40 to 80. This number is projected to increase to 111.8 million by 2040.1 Major risk factors for glaucomatous progression include high intraocular pressure (IOP),2–4 exfoliation syndrome,2 African ancestry,3–5 family history,6 increasing age,2,4,5,7,8 and thin central corneal thickness.4 IOP remains the only modifiable risk factor, and this is the reason why treatment patterns continue to evolve.
Traditionally, glaucoma is first managed with topical medications, such as prostaglandin analogues, beta-blockers, alpha-2 agonists, carbonic anhydrase inhibitors, and miotics. These medications lower IOP by inhibiting aqueous humor production and/or increasing aqueous outflow. In some cases, laser trabeculoplasty can be performed to increase outflow, in lieu of a topical medication. When patients continue to progress or are deemed likely to progress despite maximally tolerated medical therapy, incisional surgery such as trabeculectomy or tube shunt implantation is typically performed. Glaucoma surgery is known to be highly effective but can be fraught with complications. In the tube versus trabeculectomy study,6 the average IOP decreased from 25.1±5.3 to 14.4±6.9 mm Hg in the tube group and from 25.6±5.3 to 12.6±5.9 mm Hg in the trabeculectomy group at 5 years. However, 34% of patients in the tube group and 36% patients in the trabeculectomy group developed late postoperative complications, the common of which were: persistent corneal edema, dysesthesia, persistent diplopia, encapsulated bleb, bleb leak (trabeculectomy group only), choroidal effusion, cystoid macular edema, hypotony maculopathy, and tube erosion (tube group only).9 Thus, there remains a need to develop safer, less invasive surgery for the management of glaucoma.
In the early 2000s, a variety of procedures were developed so that pressure-lowering surgery could be performed through a microincisional approach without disturbing the conjunctiva. These procedures were termed “microinvasive glaucoma surgery” (MIGS), and they work in 1 of 3 ways: by decreasing resistance to outflow at the level of the trabecular meshwork (TM), inserting a shunt into the suprachoroidal space, or creating a shunt into the subconjunctival space. These surgical procedures are ideal for patients with mild to moderate glaucomatous disease, as they have shown to reduce IOP by a modest amount and have a very reasonable safety profile. Most (except possibly those that are bleb forming) are not suitable for patients with advanced disease as they cannot produce very low IOPs needed for this patient population. This review provides an update on what MIGS devices are available and how they fare in recent clinical studies.
The majority of aqueous humor outflow occurs through the TM, a circumferential band of tissue in the angle between iris and cornea. After exiting the TM, aqueous fluid travels through the endothelium-lined Schlemm’s canal and out through one of the radial collector channels. There, fluid is absorbed by episcleral veins, which drain into the anterior ciliary and superior ophthalmic veins. The juxtacanalicular TM, which is adjacent to Schlemm’s canal, is thought to be responsible for the majority of trabecular outflow resistance; therefore, devices were developed to target this resistance point.
Trabectome (NeoMedix, Tustin, CA)
Approved by the Food and Drug Administration (FDA) in 2004, this is an electrocautery device that removes a strip of TM, exposing Schlemm’s canal to the anterior chamber. The trabectome handpiece consists of irrigation and aspiration ports, a bipolar 550 kHz electrode, and a footplate at the end of tip. The surgeon makes a 1.6 mm uniplanar clear corneal incision 2 mm anterior to the limbus, tilts the patient’s head and the scope to allow for visualization of iridocorneal angle with a gonioprism, inserts the trabectome, engages the TM, and advances the device along the meshwork as irrigation, aspiration, and cautery are activated. A strip of TM is cauterized and removed as the device is advanced. The footplate is placed against the outer wall of Schlemm’s canal to protect it from thermal damage. After removing 90 degrees of meshwork, the procedure is then repeated with the device going in the opposite direction. Trabectome can be performed as a stand-alone procedure or combined with cataract extraction.
The device is designed to prevent collateral damage to surrounding tissue. When applied to human cadaver eyes, trabectome was shown to disrupt the TM and inner wall of Schlemm’s canal without damage to neighboring structures on histologic examination. In contrast, specimens that underwent goniotomy with a knife had damage to the outer wall of Schlemm’s canal and surrounding sclera.10
Minckler et al11 performed a prospective pilot study in Tijuana, Mexico, to study the effect of ab interno trabeculectomy using the trabectome. Thirty-seven patients with open-angle glaucoma were recruited. After 1 week of medication washout, the mean preoperative IOP was 28.2±4.4 mm Hg. At postoperative month 12, the mean IOP was 16.3±2.0 mm Hg. The number of glaucoma medications reduced from 1.2±0.6 preoperatively among patients on medications (n=34) to 0.4±0.6 at 6 months (n=25). Blood reflux occurred in all eyes intraoperatively and cleared on an average of 6.4±4.1 days postoperatively. All eyes had visual acuity return to within 2 lines of preoperative levels except for 1, which developed late hyphema attributed to corneal wound gape after accidental blunt trauma.
The study was then expanded to recruit a total of 101 patients with extended follow-up. The mean IOP lowered from 27.6±7.2 to 16.3±3.3 mm Hg at 30 months postoperatively (n=11). Success rate (IOP ≤21 mm Hg and no subsequent glaucoma surgery regardless of medication use) was 84%. Nine eyes underwent subsequent trabeculectomy. Intraoperative reflux bleeding was observed in all eyes but was not vision-threatening.12
There were then a number of manuscripts published by the Trabectome Study Group further evaluating the safety and efficacy of this device. A large retrospective case series13 published in 2008 evaluated 738 trabectome-only procedures. Mean IOP was reduced from 25.7±7.7 to 16.6±4.0 mm Hg at postoperative 24 months (n=46), whereas the mean number of glaucoma medications decreased from 2.9±1.30 to 1.24±0.92. Aqueous tube shunt was subsequently placed in 1.9% of eyes and trabeculectomy performed in 8.1% of eyes. There were no serious complications such as persistent hypotony, choroidal effusion, suprachoroidal hemorrhage, or infection. The Trabectome Study Group also published a prospective, nonrandomized, cohort study14 on the efficacy of trabectome (ab interno trabeculectomy) in exfoliation glaucoma (XFG) and primary open-angle glaucoma (POAG). In POAG eyes, mean IOP decreased from 25.5±7.9 to 16.8±3.9 mm Hg at 1 year. In XFG eyes, mean IOP decreased from 29.0±7.5 to 16.1±4.0 mm Hg at 1 year. The cumulative success rate was 62.9% for POAG eyes and 79.1% for XFG eyes (P=0.04). Given the pathology of XFG, it is not surprising that this procedure was more effective. Patients with POAG likely have more significant pathology in the downstream collector channels and, therefore, do not respond as well to this type of procedure.
Trabectome With Phacoemulsification (PE)
The Trabectome Study Group also published results on trabectome combined with PE. A prospective study15 on 304 eyes reported a drop in mean IOP from 20.0±6.3 to 15.5±2.9 mm Hg at 1 year postoperatively, with a simultaneous drop in glaucoma medications from 2.65±1.13 to 1.44±1.29. Blood reflux occurred in 78.4% of eyes and resolved in several days. Nine eyes required additional glaucoma surgery. This study did not have a control group of PE only.
In the study by Ting et al,14 combined surgery was performed in both POAG (n=263) and pseudoexfoliation glaucoma (PXG) (n=45) eyes. In the POAG group, mean IOP was reduced from 19.9±5.4 to 15.6±3.2 mm Hg at 1 year, whereas those in the PXG group were found to have a reduction in IOP from 21.7±8.4 to 14.2±3.2 mm Hg at 1 year. The cumulative success rate was 91.0% for the POAG group and 86.7% for those with PXG (P=0.73). Six percent of eyes with POAG and 6.4% of PXG eyes required additional glaucoma surgery. Similar to other studies, the majority of eyes (>80%) had intraoperative blood reflux but no devastating complications causing loss of >2 lines of visual acuity.
iStent (Glaukos, Laguna Hills, CA)
This iStent is a heparin-coated, titanium stent that is 1 mm in length and 0.3 mm in height. It consists of a 120 μm lumen bent ∼90 degrees with retention arches and a trephining tip at the distal end. Because the juxtacanalicular TM is thought to be a major resistance point in aqueous outflow, the iStent was designed as a trabecular bypass that allows unrestricted outflow into a portion of Schlemm’s canal.
The surgeon makes a 1.7 mm clear corneal incision and injects ophthalmic viscoelastic device (OVD) into the anterior chamber. The patient’s head and the operating microscope are tilted to allow visualization of the iridocorneal angle with a gonioprism. The iStent, attached at the end an inserter, is then inserted through the anterior third of the TM at a ∼15-degree angle (toward the sclera) and parallel to the TM. Once the retention arches are snug within Schlemm’s canal, a button on the inserter is pushed to release the device. The inserter can then be used to nudge the device into the Schlemm’s canal to ensure that the stent is secure. Blood reflux out of the stent may be observed. The iStent should ideally be placed in the inferonasal angle, as this is where most collector channels are typically located. In 2012, the FDA approved this device for use when combined with cataract surgery.
In 2010, Fea published the results of the first prospective, randomized clinical trial comparing combined iStent and PE (n=12) with PE alone (n=33). The mean preoperative IOPs were 17.9±2.6 mm Hg in the combined group and 17.3±3.0 mm Hg (P=0.51) in the control group, with no statistical significant difference between groups. The average number of preoperative glaucoma medications was 2.0±0.9 and 1.9±0.7, respectively. At postoperative month 15, mean IOP was significantly lower in the combined group (14.8±1.2 mm Hg) versus the control group (15.7±1.1 mm Hg; P=0.03). The number of glaucoma medications was also significantly lower in the combined group: 0.4±0.7 versus 1.3±1.0. However, the study was limited by its small sample size.16
Samuelson and colleagues and the US iStent Study Group performed a larger prospective, randomized clinical trial involving 240 eyes with mild to moderate open-angle glaucoma and an IOP of 22 to 36 mm Hg after medication washout. The primary endpoint was achieving IOP ≤ 21 mm Hg at 1 year, without medications. The iStent-PE (treatment) group had 72% of eyes achieve the endpoint, whereas the PE-only (control) group had 50% of eyes achieve the endpoint (P<0.001). The average reduction in IOP from preoperative to postoperative 12 months was 8.4±3.6 mm Hg in the treatment group versus 8.5±4.3 mm Hg in the control group; there was no statistical difference between groups. However, the mean decrease in glaucoma medications was higher in the treatment group (1.4±0.8) than in the control group (1.0±0.8; P=0.005). Complications unique to the treatment group were stent obstruction (4%) and stent malposition (3%). Other complications such as IOP rise and macular edema were similar to the control group.17
In 2012, Craven and colleagues published the 2-year follow-up results on the same iStent Study Group clinical trial. The primary endpoint of IOP ≤21 mm Hg without medications was achieved in 61% of eyes in the treatment group and 50% of eyes in the control group (P=0.036). For the treatment group, mean IOP was 17.0±2.8 mm Hg at 12 months and 17.1±2.9 mm Hg at 24 months. For the control group, mean IOP was 17.0±3.1 mm Hg at 12 months and 17.8±3.3 mm Hg at 24 months. The number of glaucoma medications was statistically lower in the treatment group at 12 months but not at 24 months. Complications mostly occurred during the early postoperative period with no difference between groups. Stent obstruction and malposition were managed with neodymium:YAG laser, stent repositioning, or stent replacement. As for subsequent surgeries that may affect IOP, 1 patient in the treatment group had trabeculoplasty.18
Because the iStent provided modest IOP reduction, there was interest in investigating whether placement of multiple iStents would increase efficacy. Belovay and colleagues reported a nonrandomized, prospective case series comparing the implantation of 2 iStents with cataract surgery versus 3 iStents with cataract surgery by a single surgeon. The stents were placed in the nasal TM separated by 1 to 2 clock hours. The surgeon chose to put 3 stents in eyes he deemed required more IOP control. At postoperative 1 year, the mean IOP was 14.3 mm Hg overall. The 2-stent group had a mean IOP reduction of 3.5 mm Hg and the 3-stent group 3.9 mm Hg, with no significant difference between groups (P=0.76). However, the 2-stent group was on more glaucoma medications than the 3-stent group at 1 year (P=0.04). Target IOP, as determined by the Canadian Ophthalmology Society’s evidence-based clinical practice guidelines, was achieved by 71% of eyes in the 2-stent group and 84% of eyes in the 3-stent group. The most common complication was stent occlusion (8 eyes), which was successfully managed with laser treatment to iris tissue occluding the tip of the device. One eye developed a small hyphema that resolved in 4 weeks.19
iStent Inject (Glaukos)
The iStent inject was designed to allow for direct insertion, which makes implantation easier. The device is shaped like a small spear, with a central opening where aqueous enters the stent, a circumferential central groove of which the TM will surround, and 4 sideports within the spear tip to allow for aqueous to exit into Schlemm’s canal. The inserter comes preloaded with 2 iStent devices. This device is investigational and is not yet approved by the FDA for use.
Voskanyan and colleagues performed a prospective, unmasked study in Europe to study the effect of inserting 2 iStent injects without PE. Ninety-nine eyes were enrolled. The stents were placed in the nasal angle 2 clock hours apart. Mean IOP decreased from 26.3±3.5 to 15.7±3.7 mm Hg at postoperative month 12. The primary endpoint was IOP ≤18 mm Hg without medications, and 66% of patients achieved this. Glaucoma medication burden was reduced in 86.9% of patients. Notable complications included IOP rise (10.1%, with one fifth of this group requiring trabeculectomy), stent obstruction (3%), stent malposition (1%), goniosynechiae (1%), posterior synechiae (1%), and stent not visible on gonioscopy (13%).20
Fea and colleagues conducted a prospective, unmasked, randomized clinical trial comparing insertion of 2 iStent injects with topical fixed combination of latanoprost-timolol. In the stent group (n=94), mean IOP decreased from 25.2±1.4 mm Hg (washed-out baseline) to 13.0±2.3 mm Hg at postoperative month 12. In the medication group (n=98), mean IOP decreased from 24.8 mm Hg (washed-out baseline) to 13.2±2.0 mm Hg after 12 months. When comparing the proportion of eyes with at least 50% IOP reduction, the stent group fared better (P=0.02). The authors concluded that insertion of 2 iStent injects was just as effective as 2 glaucoma medications.21
How the iStent inject fared in various types of open-angle glaucoma was evaluated by a study conducted by Klamann et al.22 In this retrospective study, 17 eyes with POAG, 15 eyes with PXG, and 3 eyes with pigmentary glaucoma (PG) had the iStent inject placed without PE. At postoperative 6 months, mean IOP when compared with preoperative baseline decreased by 33% (P<0.0001) in the POAG group and 35% (P<0.001) in the PXG group with significant decreases in number of glaucoma medications. In contrast, all 3 eyes in the PG group had IOPs increased beyond 30 mm Hg within 4 weeks postoperatively and required additional incisional glaucoma surgery. This was the first study suggesting that iStent inject may be contraindicated in PG, although the reason for failure was unclear.
Kahook Dual Blade (KDB) (New World Medical, Rancho Cucamonga, CA)
This is a stainless steel instrument with an angled tip capable of stripping off a segment of the TM. Like other angle surgeries, a clear corneal incision is made with a keratome and the anterior chamber is filled with OVD. The patient’s head is then tilted away from the surgeon and the microscope toward the surgeon and a gonioprism is placed gently on the cornea to visualize the iridocorneal angle. The instrument is inserted into the anterior chamber and the sharp tip, pointing either toward the left or right (depending on surgeon preference), engages the TM. As the instrument is advanced horizontally, the TM is lifted and stretched by a ramp just proximal to the tip. There are 2 blades along the superior and inferior edges of the ramp that excise a strip of TM. The footplate of the ramp is designed not to be sharp to prevent damage to the outer wall of Schlemm’s canal. After a certain length of TM is stripped, the blade can be flipped to the opposite direction and another strip of TM can be excised to connect with the first strip and allow for complete detachment of the entire stripped length of TM. Alternatively, the 2 strips can be performed in the same direction with connection.
The KDB was FDA-approved for use in 2015. Because the procedure is considered a goniotomy, it can be performed with or without cataract surgery as long as the iridocorneal angle is well-visualized. Seibold et al23 compared the use of KDB with the microvitreoretinal (MVR) blade, and the trabectome on cadaver eyes. In each eye, an infusion was placed underneath the iris for pressurization and a steady state IOP was maintained for 60 minutes before incision of the TM. IOP was measured with an in-line, real-time pressure transducer. MVR blade goniotomy across 170.0±14.1 degrees of TM caused IOP to decrease from 18.5±1.9 to 12.8±2.2 mm Hg (P<0.01). Trabectome cauterization across 117.5±12.6 degrees of TM caused IOP to decrease from 18.8±1.7 to 11.3±1.0 mm Hg (P<0.01). KDB use across 157.5±26.3 degrees of TM caused IOP to decrease from 18.3±3.0 to 11.0±2.2 mm Hg (P<0.01). The 3 instruments had similar reduction in IOP. Microscopic examination of the treated angle structures revealed that the MVR blade goniotomy resulted in obvious injury to adjacent sclera with minimal removal of TM. Trabectome use resulted in removal of central TM, but superior and inferior leaflets remained and thermal injury was seen. KDB use resulted in more complete removal of TM without collateral damage, due to the blade’s design.
To date, 1 single-arm, prospective study (n=71) investigated the outcomes of PE plus KDB goniotomy in mild to severe glaucoma. An average of 118.9±18.6 degrees of TM was excised in each eye. Mean IOP decreased from 17.4±5.2 to 12.8±2.6 mm Hg at postoperative month 6, whereas the number of glaucoma medications decreased from 1.6 to 0.9. Success, defined as ≥20% IOP reduction or ≥1 glaucoma medication reduction, was achieved at 6 months in 58.3% and 61.7% of eyes, respectively. The most common adverse event was intraoperative blood reflux (39.4%), which spontaneously resolved in all cases. This study served to validate the safety and efficacy of combined dual blade goniotomy and cataract surgery; however, it did not have a control PE-only group to demonstrate whether performing goniotomy had added benefit.24
Gonioscopy-assisted Transluminal Trabeculotomy
Developed at the Glaucoma Associates of Texas, this technique involves the use of a flexible, illuminated microcatheter (iTrack 250; Ellex Medical Lasers, Adelaide, Australia) or a suture to perform ab interno 360-degree trabeculotomy. First, a 23-G needle tangential paracentesis is made either superonasally or inferonasally. The anterior chamber is then inflated with OVD. An additional paracentesis is made temporally. The catheter/suture is inserted into the anterior chamber through the tangential incision and rested near the nasal angle. The patient’s head is tilted away and the microscope tilted toward the surgeon and a gonioprism is placed on the cornea for angle visualization. The microsurgical blade is advanced through the temporal wound to create a 1 to 2 mm goniotomy incision. Using microsurgical forceps, the catheter/suture is then inserted through the incision into Schlemm’s canal and advanced 360 degrees. The distal end of the catheter/suture is grasped and pulled out of the eye through the temporal corneal incision to achieve 180 degrees of trabeculotomy. The proximal end of the catheter/suture is then pulled out of the eye to complete 360 degrees. Afterwards, OVD is aspirated out of the eye, anterior chamber washed out, and OVD is reinjected (25% anterior chamber fill) to tamponade Schlemm’s canal.
Grover et al25 conducted a retrospective chart review on 85 eyes with uncontrolled glaucoma that underwent gonioscopy-assisted transluminal trabeculotomy. For eyes with POAG, mean IOP decreased by 6.2 mm Hg with an average 0.9 fewer glaucoma medications at postoperative month 6. For eyes with secondary glaucoma, mean IOP decreased by 17.2 mm Hg with an average 2.2 fewer glaucoma medications at postoperative month 6. Transient hyphema was seen in 30% of eyes at postoperative week 1. Eight eyes had inadequate IOP control postoperatively and needed additional glaucoma surgery.
For eyes that had previous incisional glaucoma surgery, Grover et al26 performed a retrospective chart review. Of the 35 eyes evaluated, 19 had prior trabeculectomy, 13 had prior aqueous tube shunt, 4 had prior trabectome, and 5 had prior endocyclophotocoagulation. Mean IOP decreased from 25.7±6.5 to 15.4±4.9 mm Hg, whereas the average number of glaucoma medications decreased from 3.2 to 2.0. Regardless of the type of previous glaucoma surgery, there was a significant reduction in IOP, with 60% of patients achieving successful IOP control.
Hydrus (Ivantis Inc., Irvine, CA)
The Hydrus microstent is an 8-mm long curved nitinol microstent that serves as a Schlemm’s canal scaffold. It consists of an inlet at one end for aqueous to enter (bypassing the TM) and 3 windows along the stent that allows for physiological flow through the TM into Schlemm’s canal. Because the back surface of the stent is not covered, the collector channel ostia are not obstructed by the implant. The stent is designed to both create a TM bypass and to keep Schlemm’s canal open. After a clear corneal incision is made and the anterior chamber filled with OVD, the patient’s head and the microscope are tilted and a gonioprism is used to visualize the angle. The microstent, preloaded in an injector, has a sharp tip at one end that is used to pierce the TM horizontally to enter Schlemm’s canal. The microstent is then advanced within Schlemm’s canal until a site interlock appears, signifying that the entire stent has been deployed and can be released from the injector. This device is investigational and is not yet approved by the FDA for use.
A prospective, clinical trial randomized eyes to Hydrus with PE and PE-only. In the Hydrus-PE group, mean baseline IOP (after wash-out) was 26.3±4.4 mm Hg preoperatively, 16.6±2.8 mm Hg at 12 months, and 16.9±3.3 mm Hg at 24 months. In the PE group, mean baseline IOP (after wash-out) was 26.6±4.2 mm Hg preoperatively, 17.4±3.7 mm Hg at 12 months, and 19.2±4.7 mm Hg at 24 months. There was no significant difference between groups except at 24 months (P=0.0093). At postoperative month 24, the percentage of eyes with at least 20% reduction in washed out diurnal IOP was 80% in the Hydrus-PE group versus 46% in the PE group (P=0.008). The average washed out diurnal IOP in the Hydrus-PE group was 16.9±3.3 mm Hg, compared with 19.2±4.7 mm Hg in the PE group (P=0.0093). More patients were using no glaucoma medications in the Hydrus-PE group (73%) than in the PE group (38%; P=0.0008). Other than development of peripheral anterior synechiae 1 to 2 mm long in the Hydrus-PE group, both groups had similar frequencies of adverse events.27
Physiologically, aqueous outflow is not limited to the TM-Schlemm’s canal-collector channel system. Aqueous humor can also percolate through the ciliary body into the supraciliary and suprachoroidal spaces, where fluid absorption by the choroid, sclera, and neighboring vasculature occurs. Studies on cat and monkey eyes revealed that the suprachoroidal space pressure is 1 to 4 mm Hg lower than IOP.28,29 This negative pressure gradient serves as a driving force for this pathway, termed uveoscleral outflow, and may be responsible for as much as 50% of aqueous drainage.30 Devices have been designed to facilitate drainage into the supraciliary and suprachoroidal spaces.
CyPass (Alcon, Fort Worth, TX)
Approved by the FDA for use in conjunction with cataract surgery in 2016, the CyPass is a nonferromagnetic polyimide stent 6.35 mm long with a 430 μm outer diameter and a 300 μm lumen. At the proximal end, there are a collar and 3 retention rings. The rest of the stent has 64 fenestrations that allows for outflow from the lumen to the supraciliary space. Like other angle surgeries, the anterior chamber is filled with OVD, the patient’s head and the microscope are tilted, and a gonioprism is used to visualize the angle. The CyPass, attached at the end of a curved guidewire, is inserted between the scleral spur and ciliary body following the downward curvature of the sclera, and then released when only the most proximal retention ring and the collar are in the anterior chamber.
A prospective clinical trial was conducted evaluating CyPass use with PE in eyes with open-angle glaucoma. The patients were divided into 2 groups: those with uncontrolled IOP (≥21 mm Hg) on medications and those with controlled IOP (< 21 mm Hg) on medications. At 6-month follow-up, the uncontrolled glaucoma group (n=57) had a mean 37% IOP reduction (P<0.001), along with a 50% reduction in glaucoma medications (P<0.001). In the controlled glaucoma group (n=41), the mean postoperative month 6 IOP was 15.6±0.68 mm Hg and the number of glaucoma medications decreased by 71.4% (P<0.001). The mean preoperative IOP in this group was not stated.31 The 12-month follow-up results were subsequently published.32 Both cohorts were able to maintain low average IOPs similar to the 6-month follow-up, with the uncontrolled glaucoma group at 16.3±3.4 mm Hg and the controlled glaucoma group at 15.7±3.0 mm Hg. The number of glaucoma medications was similar from 6 months prior in both groups as well. The most common adverse event was hypotony, which occurred in 13.8% of all eyes and resolved by 1-month postoperatively without surgical intervention. None had shallowing of the anterior chamber, choroidal effusion, suprachoroidal hemorrhage, or hypotony maculopathy. Other implant-related complications included hyphema (1.2% of all eyes), endothelial touch (1.2%), stent obstruction (5.4%), requirement for stent repositioning (0.6%), and requirement for stent explantation (0.6%). An IOP spike >10 mm Hg from baseline occurred in 1.2% of eyes within 1 month of surgery and 1.8% of eyes after 1 month of surgery. Additional glaucoma surgery was performed in 6% of eyes.
Although the previous study investigated the safety and efficacy of using CyPass in conjunction with cataract surgery, it did not have a PE-only control group to demonstrate added benefit of CyPass insertion. Thus, a multicenter, randomized, clinical trial33 with a control group was conducted in the United States. At baseline, the mean IOPs in the PE-CyPass and PE-only groups were 24.5±3.0 and 24.4±2.8 mm Hg, respectively (P>0.05), and the mean numbers of medications were 1.3±1.0 and 1.4±0.9, respectively (P>0.05). The primary endpoint was 20% IOP reduction without medications. This endpoint was achieved by 77% of eyes in the CyPass group and 60% of eyes in the control group (P=0.001) at 24 months. The average IOP decrease was 7.4 mm Hg in the CyPass group and 5.4 mm Hg in controls (P<0.001). The average number of glaucoma medications at 24 months was 0.6±0.8 in the CyPass group and 0.2±0.6 in the control group. Complications associated with the CyPass procedure included: corneal edema (3.5%), cyclodialysis cleft >2 mm (1.9%), transient intraoperative hyphema (2.7%), iritis (8.6%), hypotony (2.9%), IOP rise at least 10 mm Hg above baseline (4.3%), and cystoid macular edema (1.3%). Stent obstruction occurred in 2.1% of CyPass group eyes. None in the CyPass group had vision-threatening stent-related adverse events.
iStent SUPRA (Glaukos)
This ∼4-mm-long curved stent consists of a 165 μm lumen, a proximal titanium sleeve, and retention rings distally. Similar to the CyPass, it is placed ab interno through a clear corneal incision and introduced in between the scleral spur and ciliary body. A randomized clinical trial is undergoing, and it is not FDA-approved for use in the United States at this time.
Directing aqueous humor to the subconjunctival space has been successful in lowering IOP, as demonstrated by traditional glaucoma surgeries such as trabeculectomy and tube shunt surgery. As a result, there is great interest in developing a bypass stent into the subconjunctival space that is safer than these traditional procedures.
XEN Gel Stent (Allergan, Dublin, Ireland)
This is the only ab interno subconjunctival stent available at this time. It is a 6-mm long stent made of porcine gelatin cross-linked with glutaraldehyde. There are 3 models with various luminal diameters: 140, 63, and 45 μm. The narrower the lumen, the greater the resistance to flow. To insert the implant, a clear corneal incision is made inferotemporally 1 mm away from the limbus. OVD is injected into maintain the anterior chamber. A mark is made on the conjunctiva 3 mm from the limbus in the superonasal quadrant; this is the point intended for the stent to emerge from the sclera into the subconjunctival space. A 27-G needle with the stent preloaded is then inserted into the anterior chamber and directed toward the superonasal iridocorneal angle. A gonioprism can be used to ensure that the needle enters at the level of the TM or just anterior to it before passing the needle through the angle. The needle is advanced so that it emerges from the sclera at the mark. Care is taken to advance the needle until the entire bevel tip is visible without penetrating the conjunctiva. A button on the injector is then advanced forward to inject the stent and retract the needle. Ideally, the stent distal tip should be located just subconjunctival, above Tenon’s layer, to avoid occlusion, and then 1 mm of the stent remains in the anterior chamber. If the stent is curved subconjunctivally, a blunt instrument can be used to apply pressure externally, over the conjunctiva, to roll and straighten out the stent. This procedure can be performed with or without cataract surgery. Adjunctive mitomycin-C should be used to the enhance success of the smaller lumen models.
A prospective, nonrandomized trial investigated the use of the XEN140 stent in eyes with open-angle glaucoma with 12-month follow-up. No mitomycin C was used intraoperatively. Mean IOP decreased from 23.1±4.1 to 14.7±3.7 mm Hg. Success was defined as postoperative IOP≤18 mm Hg and ≥20% reduction from baseline; this was achieved by 89% of eyes with glaucoma medications and 40% of eyes without glaucoma medications. Of the 49 eyes enrolled, 3 required subsequent glaucoma surgery. Four eyes had dispersive OVD injected intracamerally at postoperative week 1 for shallow anterior chamber; there were no choroidal effusions and normal anterior chamber depth was restored 1 week after injection. Needling was performed in 47% of eyes and resulted in a postneedling mean IOP of 13.2±4.8 mm Hg at postoperative month 12. No serious adverse events such as endophthalmitis, implant exposure or migration, choroidal effusion or hemorrhage, or retinal detachment was observed.34
Whether a stent with a smaller lumen, which provides protection from hypotony with increased resistance to flow, can effectively lower IOP was investigated next. A prospective, nonrandomized study (n=41) conducted in Europe evaluated the safety and efficacy of using the XEN45 Gel Stent in combination with cataract surgery. In contrast to the XEN140 study, this study involved the use of mitomycin C (0.1 mL of 0.1 mg/mL) injection subconjunctivally before PE and stent insertion. Mean IOP decreased from 22.5±3.7 (on an average of 2.5±0.9 glaucoma medications) to 13.1±2.4 mm Hg (on an average of 0.4±0.8 glaucoma medications) at postoperative month 12. Success, defined as postoperative IOP 6 to 17 mm Hg, was achieved by 80.4% of eyes on no glaucoma medications. One eye required needling, 1 required implant explantation, 1 had stent obstruction, and 1 had stent migration. Transient hypotony with choroidal detachment occurred in 1 eye and resolved without intervention in 1 week.35
A pivotal US study (n=65) on the XEN45 Gel Stent was conducted with the use of mitomycin C-soaked sponges, as mitomycin C injection was considered off-label in the United States. The conjunctiva had to be opened (and later closed) to place the sponges before the stent was inserted using an ab interno approach. Preoperative mean IOP was 25.1±3.7 mm Hg. At postoperative month 12, mean IOP was 9.1 mm Hg lower, with the number of glaucoma medications reduced from 3.5 to 1.7. The primary endpoint, defined as at least 20% IOP reduction from baseline on the same number or fewer glaucoma medications, was achieved by 75.4% of eyes at 12 months. Notably, 24.6% of patients had transient hypotony that did not require surgery, 32.3% of patients had needling done, and 21.5% of patients had an IOP increase of at least 10 mm Hg. There were no reports of choroidal effusion, suprachoroidal hemorrhage, or maculopathy.36
A wide variety of MIGSs have been developed to provide surgeons and patients with a safer approach to glaucoma surgery. Reasonable efficacy has been shown with most procedures and newer studies are constantly being performed to provide us with better data. Although the pressure reduction does not match those of traditional glaucoma surgeries such as trabeculectomy and tube shunt implantation, MIGSs have significantly fewer adverse events and can play a role in slowing disease progression and reducing medication burden for eyes with mild to moderate glaucoma.
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