Evaluation of iStent® Inject W in mild to moderate primary open-angle glaucoma – Indian data on pseudophakic eyes

Abstract

Purpose:

This study aimed to evaluate the safety and efficacy of standalone bilateral iStent® Inject W implantation in pseudophakic patients with mild to moderate primary open-angle glaucoma (POAG) over 18 months.

Design:

Prospective, longitudinal study.

Methods:

Twenty-eight pseudophakic eyes with mild to moderate POAG were implanted with iStent® Inject W. Outcome measures included intraocular pressure (IOP) and change in the number of antiglaucoma medications.

Results:

The mean IOP declined from 21.14 ± 2.18 mmHg preoperatively to 15.14 ± 1.51 mmHg at 18 months postoperatively (P < 0.0001), while the average number of antiglaucoma medications was reduced from 2.07 ± 0.73 to 1.18 ± 0.83 over the same period (P < 0.05).

Conclusion:

Standalone iStent® Inject W implantation in pseudophakic patients with mild to moderate POAG results in a sustained reduction in IOP and the number of antiglaucoma medications at 18 months postoperatively.

 

Glaucoma, a chronic, progressive, and irreversible optic neuropathy, is the leading cause of irreversible blindness globally, affecting approximately 100 million people.[1,2,3,4] Primary open-angle glaucoma (POAG) represents the most prevalent form.[3,5,6] To date, intraocular pressure (IOP) reduction remains the sole modifiable risk factor for preventing glaucomatous vision loss.[7,8]

Over the last decade, minimally invasive glaucoma surgery (MIGS) has emerged as a therapeutic modality in the management of glaucoma.[9] MIGS devices are broadly classified into three categories based on their anatomical site of action and mechanism of outflow enhancement. MIGS serves as a bridge between pharmacological therapy and conventional filtering surgeries.[10] MIGS provides effective IOP reduction with minimal surgical risk.[11]

The iStent® Inject W (Glaukos Corporation, San Clemente, CA, USA) is a third-generation iStent designed to drain aqueous humor from the anterior chamber (AC) into Schlemm’s canal (SC), bypassing the trabecular meshwork (TM).[12,13]

This study evaluated the safety and efficacy of bilateral iStent® Inject W implantation in pseudophakic patients with mild to moderate POAG over 18 months.

Methods

A prospective, longitudinal study to evaluate the safety and efficacy of the iStent® Inject W in pseudophakic patients with mild to moderate POAG with bilateral implantation at the end of an 18-month follow-up. After institutional human ethics committee approval (IHEC no: BB/Res/01/2024/82/IHEC/071), the study enrolled 28 eyes of 14 patients who met the inclusion criteria. Before inclusion, all patients were comprehensively informed about the study’s purpose and provided written informed consent. The standalone iStent inject W was offered as an alternative treatment option to patients who wanted to reduce the medication burden. The duration of the study was from June 2023 to February 2025. Approval was obtained from the institutional ethics committee and is consistent with the tenets of the Declaration of Helsinki.

Patients aged between 40 and 75 years with bilateral pseudophakia and a diagnosis of mild to moderate POAG, with IOP maintained below 26 mmHg on one to three topical antiglaucoma agents, were included in the study. Glaucoma severity was classified according to the Hodapp–Anderson–Parrish criteria based on 24-2 Swedish Interactive Thresholding Algorithm (SITA) Standard program on Humphrey Field Analyzer (Carl Zeiss Meditech, Dublin, CA). Glaucoma was categorized as Mild: mean deviation (MD) of 0 to –6 dB; Moderate: MD of >–6 to –12 dB with no evidence of central visual field involvement. Open-angle glaucoma was defined as a gonioscopic Shaffer grade of ≥3 in all four quadrants, with no evidence of peripheral anterior synechiae (PAS) or significant pigmentation, thus excluding secondary or angle-closure glaucoma.

Patients with other forms of glaucoma, including primary angle-closure or secondary glaucomas, as well as those with advanced-stage disease, were excluded. Additional exclusion criteria included prior laser or surgical glaucoma interventions, active inflammation or edema of the cornea, a history of corneal surgery, or any pathology that obstructed visualisation of the nasal angle. Moreover, patients presenting with elevated episcleral venous pressure due to conditions such as retrobulbar tumors, thyroid eye disease, or Sturge–Weber syndrome were not included.

All patients underwent a comprehensive preoperative ophthalmic evaluation, which included best-corrected visual acuity (BCVA) assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) charts under photopic conditions, slit-lamp examination, IOP measured by Goldmann applanation tonometry (GAT), number of medications recorded, gonioscopy with Sussman 4 mirror gonio-lens (Model 72004, Ocular instruments, USA) with grading documented in all four quadrants using the Shaffer grading scale, dilated fundoscopy, and central corneal thickness (CCT) determined with a specular microscope (Topcon SP-1P, Japan). A visual field (VF) test was also conducted using the 24–2 SITA Standard program on the Humphrey Field Analyzer (Carl Zeiss Meditech, Dublin, CA).

All the patients received topical antibiotic prophylaxis preoperatively. All surgeries were performed by a single surgeon under topical anesthesia utilizing 0.5% Proparacaine. A temporal clear corneal incision of 2.4 mm was made. An ophthalmic viscosurgical device (OVD), 1.8% sodium hyaluronate, was injected to deepen and maintain the AC. The patient’s head was positioned at a 25° tilt away from the surgeon, while the surgical microscope was inclined at a 35° angle toward the surgeon. A surgical gonioscopic lens (iPrism^® SX, Glaukos Corporation, San Clemente, CA, USA) is placed on the cornea to obtain proper AC angle viewing. The microscope was adjusted (10-12x) to visualize the TM, through the surgical gonioscopic lens, on the nasal side of the eye. The iStent^® Inject W is inserted through the temporal incision and advanced past the pupillary margin. The injector sleeve was retracted, exposing the trocar and micro-insertion tube. The trocar was advanced through the center or slightly anterior portion of the TM and into the posterior wall of SC. The delivery button was then activated to deploy the first stent, followed by the implantation of the second stent laterally, positioned 2 to 4 clock hours away from the first. The OVD was removed, and the AC was filled with balanced saline solution. The incision was hydrosealed to ensure proper closure of the wound.

Postoperatively, patients were prescribed antibiotics for 1 week and steroid eyedrops for 1 month, which started as six times per day and were gradually tapered every week. Postoperatively, patients attended follow-up visits as per local protocols at day 1 (POD 1), 1 week (POW 1), 1 month (POM 1), 2 months (POM2), 3 months (POM 3), 6 months (POM 6), 12 months (POM 12), and 18 months (POM 18).

iStent^® Inject W implantation was done in a unilateral, sequential fashion on different days. Following bilateral implantation of iStent^® Inject W, outcome measurement was done by collecting data at an 18-month postoperative visit, ranging from 18 to 20 months after surgery. BCVA was assessed using Early ETDRS charts under photopic conditions, IOP was measured by GAT, the number of medications was recorded, and VF testing was conducted using 24–2 SITA Standard program on Humphrey Field Analyzer (Carl Zeiss Meditech, Dublin, CA).

Statistical analysis

Variables were expressed as mean ± SD and 95% confidence interval. A parametric paired t-test procedure was used to determine the significance of the mean change in IOP from baseline to each postoperative visit. A nonparametric McNemar’s Chi-squared test was used for analysis of the number of glaucoma medications from baseline to each postoperative visit. All the statistical analyses were carried out using the statistical software R version 4.3.0. P value < 0.05 is considered significant.

Results

This prospective study investigated 28 eyes of 14 patients. The mean age of the study participants was 61.8 ± 8.0 years. All patients had a prior diagnosis of mild to moderate POAG. These characteristics, along with additional baseline data, are presented in Table 1.

Table 1.

Patient demographics and baseline characteristics

Variable		Value
Eyes (n)		28
Age (mean ±SD)		61.8± 8.0
Glaucoma severity [n, (%)]
Mild		15
Moderate		13
Preoperative CCT (µm; mean±SD)		526±34
Preoperative Mean Deviation (dB; Mean±SD)		6.8±3.4
Preoperative IOP (mmHg; mean±SD)		21.14±2.18
Preoperative medication score (mean±SD)		2.07±0.73

Table 2 presents the mean IOP measured at each postoperative visit, compared to the preoperative IOP, which served as the baseline. At baseline, the mean IOP was 21.14 ± 2.18 mmHg. At 12 months postoperatively, the mean IOP was 15.57 ± 1.40 (P < 0.0001). This reduction was sustained at 18 months postoperatively, 15.14 ± 1.51 (P < 0.0001) (Power 1), indicating an IOP reduction of 6.00 ± 2.22 (27.86%).

Table 2.

Overview of the change in intraocular pressure from baseline to each postoperative visit

		Mean preoperative IOP		Mean postoperative IOP		Mean IOP difference (P)		Percentage reduction in IOP from baseline		95% CI for mean
POD 1		21.14±2.18		18.29±1.54		2.86±1.41 (<0.0001*)		13.19%		(3.264, 4.164)
POW1		21.14±2.18		18.07±1.71		3.07±1.41 (<0.0001*)		14.28%		(4.3, 5.7)
POM1		21.14±2.18		17.57±2.10		3.57±1.16 (<0.0001*)		16.88%		(2.551, 3.591)
POM3		21.14±2.18		16.14±1.75		5.00±1.88 (<0.0001*)		23.32%		(2.337, 3.377)
POM6		21.14±2.18		16.14±1.75		5.00±1.88 (<0.0001*)		23.32%		(3.141, 4.001)
POM12		21.14±2.18		15.57±1.40		5.57±1.78 (<0.0001*)		25.97%		(4.911, 6.231)
POM18		21.14±2.18		15.14±1.51		6.00±2.22 (<0.0001*)		27.86%		(5.18, 6.82)

Table 3 illustrates the mean number of antiglaucoma medications used at each postoperative visit. At baseline, the mean number of antiglaucoma medications was 2.07 ± 0.73. Combination antiglaucoma eye drops were classified as two separate medications in the analysis. At 12 months postoperatively, the mean number of antiglaucoma medications was 1.32 ± 0.88 (P < 0.05). This reduction was sustained at 18 months postoperatively, 1.18 ± 0.83 (P < 0.05) (power 0.93), indicating a mean number of antiglaucoma medication reduction of 0.89 ± 0.89.

Table 3.

Overview of the change in number of antiglaucoma medications from baseline to each postoperative visit

		Mean preoperatively no. of meds		Mean postoperatively no. of meds		Mean meds difference (P)		95% CI for mean
POD 1		2.07±0.73		1.5±0.52		0.57±0.70 (<0.01*)		0.31 - 0.83
POW1		2.07±0.73		1.57±0.51		0.50±0.71 (<0.05*)		0.24 - 0.76
POM1		2.07±0.73		1.57±0.51		0.500±0.81 (<0.05*)		0.2 - 0.8
POM3		2.07±0.73		1.32±0.88		0.75±0.76 (<0.05*)		0.45 - 1.05
POM6		2.07±0.73		1.36±0.69		0.71± 0.82 (<0.05*)		0.41 - 1.02
POM12		2.07±0.73		1.32±0.88		0.75±0.76 (<0.05*)		0.47 - 1.03
POM18		2.07±0.73		1.18±0.83		0.89±0.89 (<0.05*)		0.56 - 1.22

In terms of safety, all eyes successfully underwent standalone implantation of iStent® Inject W devices. Mild hyphema occurred intraoperatively in two eyes and resolved without intervention or sequelae by the first postoperative week. Throughout the follow-up period, no IOP spikes or device-related adverse events were reported. There were no instances of hypotony, PAS, stent obstruction, or corneal decompensation. Furthermore, none of the eyes required secondary glaucoma surgery.

Discussion

In the present study, comparing outcomes in terms of IOP-lowering effect and number of antiglaucoma medications in pseudophakic patients with mild to moderate glaucoma, a mean decrease of IOP of 6.00 ± 2.22 mmHg (27.86%, p < 0.0001) and number of antiglaucoma medications of 0.89 ± 0.89 (P < 0.05) was observed postoperatively at 18 months from baseline. In glaucoma, IOP is the primary modifiable risk factor, and it plays a key role in its progression.[14,15] The Early Manifest Glaucoma Trial (EMGT) demonstrated that the risk of glaucoma progression decreased by 10% each 1-mmHg reduction in IOP from baseline.[16] Given its progressive course, glaucoma management focuses on maintaining target IOP to preserve vision while minimizing the negative impact on the patient’s quality of life.[17,18,19] Conventional management of glaucoma primarily includes pharmacologic and laser-based interventions, which are generally associated with a lower risk profile compared to traditional incisional glaucoma filtering surgeries.[20]

However, chronic use of antiglaucoma medication has been frequently associated with ocular side effects and reduced compliance.[21,22] Shu YH et al.[23] in a study demonstrated poor compliance to medical therapy as a direct risk for the functional progression of glaucoma.

Filtering surgeries are associated with significant risks of intraoperative and postoperative complications that may threaten vision, including hypotony, infection, suprachoroidal hemorrhage, and the potential requirement for further surgical procedures.[24] Regarding the risk of complications, MIGS represents an intermediate option, positioned between pharmacological treatment and traditional surgical approaches.[20,25]

The iStent® Inject W device obtained FDA approval in 2020 as an updated iteration of the second-generation iStent Inject. Alongside, iStent Inject W is approved by CDCSO (Central Drugs Standard Control Organization of India) and DCGI (Drug Controller General of India) for a standalone procedure in pseudophakic eyes. The device features a broader flange to enhance intraoperative visualization and facilitate precise placement.[26,27] The 360-μm heparin-coated titanium stent is implanted ab interno through the TM, with its head in SC and flange in the AC. Each stent features an 80-μm central inlet and outlet, plus four 50-μm side outlets for aqueous drainage, supplied in a preloaded injector with two stents.[28] The dual iStent procedure requires a single eye entry, reducing surgery time and complication risk.[29,30] Following implantation of the iStent® Inject W, aqueous humor is diverted from the AC directly into SC, effectively bypassing the TM.[12,13] It stabilizes IOP, improves compliance, slows disease progression, and, when done early, preserves vision and minimizes long-term effects of eye drops.[31,32,33,34]

The current study shows a mean decrease of IOP of 6.00 ± 2.22 mmHg (27.86%, P < 0.0001), and a number of antiglaucoma medications of 0.89 ± 0.89 (P < 0.05) was observed. To the best of our knowledge, there are no prior studies that have specifically evaluated the IOP-lowering efficacy of the iStent® Inject W in pseudophakic eyes diagnosed with POAG under medication. However, Ferguson TJ et al.[35] assessed the safety and efficacy of the previous generation iStent Trabecular Micro-Bypass in pseudophakic patients with open-angle glaucoma, showing a mean IOP reduction from 20.26 ± 6.00 mm Hg preoperatively to 16.34 ± 3.78 mm Hg at 1 year and 13.62 ± 4.55 mm Hg at 2 years (P < 0.01). Although a reduction in glaucoma medications was observed (1.95 ± 1.01 to 1.69 ± 1.28), it was not statistically significant. In a study conducted by Mendoza-Moreira AL et al.,[36] a mean reduction in IOP of 2.4 mmHg (P < 0.001) and number of antiglaucoma medications of -1.67 (P < 0.001) postoperatively at 12 months after implantation of iStent Inject® W combined with phacoemulsification were observed.

In our study, a significant reduction in IOP was observed postoperatively, with a mean decrease of 5.00 ±1.88 mmHg (23.32%, P < 0.0001) at POM3. This reduction remained consistent at 6 months (5.00 ± 1.88,23.32%, P < 0.0001), 12 months (5.57 ± 1.78 mmHg; 25.97%, P < 0.0001), and 18 months (6.00 ± 2.22 mmHg; 27.86%, P < 0.0001). In a study conducted by Kanda et al.,[37] implantation of the iStent® Inject W in conjunction with cataract surgery resulted in a statistically significant reduction in mean IOP, decreasing from 16.5 ± 3.5 mmHg preoperatively to 13.7 ± 2.5 mmHg at 12 months postoperatively (P < 0.001). Additionally, statistically significant IOP reductions were noted at 1, 3, 6, and 9 months following surgery compared preoperative values (P = 0.02, P < 0.001, P < 0.001, and P < 0.001, respectively). Morita S et al.[38] in a study on implantation of iStent Inject W with cataract surgery for POAG and normal tension glaucoma showed a significant reduction (P < 0.01) in IOP from 15.0 ± 2.8 to 13.6 ± 2.9 mmHg at POM1, 15.0 ± 2.8 to13.4 ± 2.7 mmHg at POM3, and 15.0 ± 2.8 to 13.8 ± 3.3 mmHg at POM12. Deneri S et al.[39] showed statistically significant reduction in IOP both immediately postoperative from 16.08 ± 3.27 to 12.65 ± 3.17 mmHg (P < 0.01) and after 6 months from 16.08 ± 3.27 to 13.88 ± 2.57 mmHg (P < 0.01) on implantation of iStent Inject W with cataract surgery for open-angle glaucoma. The exact extent to which the iStent® Inject W alone contributes to IOP reduction remains unclear in the above studies, given that the procedure was performed concurrently with cataract surgery, which itself is known to significantly lower IOP.

The present study demonstrated a reduction in the number of antiglaucoma medications from 2.07 ± 0.73 to 1.18 ± 0.83 (P < 0.05) at 18 months postoperatively. It also had a significant reduction in number of antiglaucoma medications at POD1, POW1, POM1, POM2, POM3, POM6, and POM12 months postoperatively than preoperatively (P < 0.01, P < 0.05, P < 0.05, P < 0.01, P < 0.05, P < 0.05, P < 0.05, respectively). At the end of the 18 months, 21.43% (n = 6) of eyes were medication-free, and 32.14% (n = 9) of eyes were reduced to a single medication. Kanda et al.[37] showed a reduction in antiglaucoma medication from 2.3 ± 1.2 to 1.0 ± 1.0 (P < 0.001) at 12 months postoperatively after iStent Inject W was implanted during cataract surgery. Morita S et al.[38] in a study on implantation of iStent Inject W with cataract surgery for POAG and normal tension glaucoma showed a statistically significant reduction in the mean number of medications in all postoperative visits in a 12-month-long study (P < 0.01).

Deneri S et al.[39] in a study on implantation of iStent Inject W with cataract surgery for open-angle glaucoma demonstrated a reduction in glaucoma medication immediate postoperation from 2.69 ± 1.03 to 1.5 ± 1.39 and after 6 months from 2.69 ± 1.03 to 2.06 ± 1.34. Iwasaki et al.[28] evaluated the outcomes of iStent Inject® W combined with cataract surgery at 12 months and showed a reduction of the mean number of glaucoma medications from 2.5 ± 1.2 to 0.5 ± 0.9 (P < 0.01). In this regard, Kader MA et al.[40] showed that the IOP reduction after phacoemulsification in patients with POAG was 2.14 ± 1.33 mm Hg.

A meta-analysis conducted by Malvankar-Mehta MS et al.[41] showed that solo iStent implantation without concurrent cataract extraction effectively lowers IOP and reduces medication burden, where the maximum reduction is seen at 12 months and the effect is sustained for at least 18 months. The results of this meta-analysis are in concordance with our study, which shows a maximum reduction at 18 months, followed by a reduction at 12 months. Healey PR et al. in their meta-analyses of eyes implanted with iStent devices observed a 31.1% mean IOP reduction at 6 to 12 months.[42]

All eyes underwent successful standalone implantation of the iStent® Inject W without any serious adverse effects. This is similar to previous studies on iStent® Inject W that have reported low incidences of adverse events, with hyphema and transient elevations in IOP being the most commonly observed postoperative complications.[36,37,38]

This study has certain limitations, most notably the relatively small sample size and lack of a control group; all patients had well-controlled POAG on presentation and single surgeon, which makes the results not generalizable. Additionally, since both eyes of the patient were included to calculate IOP reduction and medications after iStent Inject W implantation, the crossover effect of medication postoperatively may influence the reduction in medication. Future research should consider employing larger cohorts and assessing long-term outcomes, particularly in terms of IOP reduction and its clinical correlation with visual field progression.

Although previous studies have shown significant IOP reduction with combined cataract extraction and iStent inject or iStent® Inject W implantation in patients with mild to moderate glaucoma, our study demonstrates that iStent® Inject W as a standalone procedure in pseudophakic patients with POAG is equally effective, achieving a 27.86% reduction in IOP after 18 months. The standalone use of the iStent® Inject W allows for a more precise determination of its IOP-reducing efficacy than when combined with phacoemulsification.

Conclusion

iStent® Inject W implantation in pseudophakic patients with mild to moderate glaucoma, independent of cataract surgery, offers sustained reduction in IOP and number of antiglaucoma medications at 18 months, supporting earlier surgical intervention and potentially decreasing dependence on topical therapies.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.