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This was a prospective, randomized, double-masked, multicenter, 24-month study to compare effectiveness and safety outcomes following standalone implantation of two types of current generation trabecular stents in adults with open-angle glaucoma (OAG). An interim analysis was performed at month 6.
Methods
Eyes with OAG, mean IOP ≤ 24 mmHg on zero to three intraocular pressure (IOP)-lowering medications at screening, and with baseline mean diurnal IOP (MDIOP) 21–36 mmHg after medication washout were randomized to standalone implantation of the current generation of three trabecular micro-bypass stents (iStent infinite) or one trabecular bypass stent (Hydrus). Eyes on medication were to undergo a medication washout prior to the month 6 visit. Analyses included a comparison of the proportion of iStent infinite versus Hydrus eyes achieving MDIOP reduction of 20% or greater from baseline at month 6. Reduction from baseline in MDIOP and number of medications were also assessed. Safety parameters included intraoperative/postoperative complications, corrected visual acuity, slit-lamp biomicroscopy, ophthalmoscopy, gonioscopy, perimetry, and adverse events.
Results
Eyes with primarily mild-to-moderate disease severity were randomized: 91 iStent infinite eyes had screening mean (± standard deviation [SD]) IOP of 17.0 ± 3.2 mmHg on 1.6 ± 0.9 medications and baseline unmedicated MDIOP of 23.7 ± 2.9 mmHg; 89 Hydrus eyes had screening mean (± SD) IOP of 17.1 ± 3.3 mmHg on 1.5 ± 0.9 medications and baseline unmedicated MDIOP of 23.5 ± 2.7 mmHg. At month 6, a similar proportion of iStent infinite eyes (82.7%) versus Hydrus eyes (78.9%) achieved MDIOP reduction ≥ 20% from baseline regardless of IOP medication use or surgical complications. The difference was statistically significantly different (78.2% iStent infinite versus 65.0% Hydrus) for unmedicated MDIOP reduction ≥ 20% from baseline in eyes with no surgical complications (difference 13.2%; 95% confidence interval (CI) 3.0%, 23.3%). Mean MDIOP change from baseline, regardless of IOP medication use or surgical complications, was similar between groups (− 7.4 ± 2.9 mmHg iStent infinite and − 7.2 ± 2.9 mmHg Hydrus), whereas unmedicated MDIOP change from baseline without surgical complications was statistically significantly superior in iStent infinite eyes (− 6.8 ± 4.1 mmHg) versus Hydrus eyes (− 5.7 ± 4.1 mmHg) (difference − 1.1 mmHg; 95% CI − 2.0 mmHg, − 0.2 mmHg). Improper stent placement was reported in one iStent infinite and seven Hydrus eyes (1.1% versus 7.9%). One iStent infinite versus four Hydrus eyes experienced peripheral anterior synechiae > 1 mm (1.1% versus 4.5%). Overall, there were significantly fewer surgical complications in the iStent infinite eyes (3.3%) compared to Hydrus eyes (16.9%; difference of − 13.6%, 95% CI − 23.8%, − 3.4%).
Conclusions
In this study of standalone implantation of current trabecular stent technologies in subjects with OAG, high proportions in both groups achieved clinically meaningful IOP reduction. When considering surgical complications as failures, a statistically significantly greater proportion of iStent infinite eyes versus Hydrus eyes had no surgical complications and achieved an unmedicated MDIOP reduction of ≥ 20%. The iStent infinite group also had clinically relevant and statistically significantly superior reduction from baseline in unmedicated MDIOP without surgical complications compared to Hydrus.
Trial Registration
ClinicalTrials.gov identifier, NCT05127551.
Key Summary Points
Two trabecular meshwork stent technologies are available to patients with open-angle glaucoma.
This study compared the intraocular pressure (IOP)-lowering effectiveness of the current generation of two different trabecular bypass stents (iStent infinite trabecular micro-bypass stent and Hydrus microstent) and incorporated a composite endpoint based on an IOP-lowering medication washout and surgical complications in order to characterize the performance of the two technologies.
At month 6, both groups achieved a high degree of similar and clinically meaningful IOP reduction without consideration of surgical complications and medication washout.
When incorporating surgical complications, the iStent infinite group demonstrated a higher success rate compared to the Hydrus stent group and produced a statistically significant superior unmedicated IOP-lowering treatment effect.
This study of current trabecular stent technologies produced high-quality evidence of the benefits of iStent infinite and Hydrus with iStent infinite outperforming Hydrus when considering both effectiveness and surgical complications.
Introduction
Glaucoma, a leading cause of irreversible vision impairment worldwide, describes a group of conditions in which there is characteristic cupping of the optic disc with corresponding visual field defects due to retinal ganglion cell loss. Open-angle glaucoma (OAG), a subset of glaucoma, is defined by an open, normal appearing anterior chamber angle and raised intraocular pressure (IOP). IOP is considered the most important risk factor for the development of OAG and remains the only known modifiable risk factor.
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Management of OAG requires life-long treatment to maintain vision and preserve the visual field. Although IOP-lowering medications have traditionally served as the initial treatment for OAG, in recent years, therapies such as selective laser trabeculoplasty, minimally invasive glaucoma surgery (MIGS), and procedural pharmaceuticals (i.e., iDose TR [travoprost intracameral implant] 75 μg, Durysta [bimatoprost intracameral implant] 10 μg) have been advanced as alternative approaches to lower IOP earlier in the treatment paradigm [1]. These therapies result in minimal trauma to tissue and reduce topical medication burden which is often associated with ocular surface disease [2], decreased quality of life, and non-adherence [3].
Commercially available trabecular stenting MIGS devices include the iStent trabecular micro-bypass family of devices (Glaukos Corporation, Aliso Viejo, CA) and Hydrus® Microstent (Alcon Inc., Fort Worth, TX), both of which are designed to lower IOP by enhancing conventional aqueous outflow. Since 2004, there have been four generations of iStent technology, starting with the original iStent model, the first MIGS device (available in Europe in 2004 and in the USA in 2012), progressing to the iStent inject (2010) and iStent inject W (two stents of new design; 2019), and most recently the iStent infinite® Trabecular Micro-Bypass System (three stents of new design in a single injector; 2022).
Several recent publications have reported on the outcomes of studies comparing original first-generation iStent or second-generation iStent inject models versus the current generation Hydrus in a standalone procedure or in combination with phacoemulsification in patients with OAG [4‐9]. Reviews have found that both the iStent series (iStent and iStent inject) and Hydrus produced comparable IOP-lowering effectiveness and safety outcomes with the addition of multiple iStent devices conferring added benefit [10].
The objective of this study was to conduct a prospective, randomized, multicenter, head-to-head evaluation of the effectiveness and safety outcomes of the current technology—iStent infinite versus Hydrus administered as a standalone procedure in subjects with OAG. The iStent infinite evaluated in this study is the current fourth-generation iStent technology comprising three stents. This analysis reports on the 6-month safety and effectiveness of this ongoing 24-month trial.
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Methods
Design
This was a prospective, randomized, parallel-group, two-arm, double-masked (subjects and IOP outcomes assessor) clinical study conducted in seven ophthalmology clinics in Canada, New Zealand, Armenia, and Honduras. Thirteen ophthalmologists, highly trained in MIGS surgery, and with extensive experience in implanting both iStent and Hydrus technology performed the surgeries. Human subjects were included in this trial. The trial was undertaken in accordance with the tenets of the Declaration of Helsinki, and the protocol, consensus ethical principles derived from international guidelines and Council for International Organizations of Medical Sciences (CIOMS) International Ethical Guidelines, applicable ICH Good Clinical Practice (GCP) Guidelines, and applicable laws and regulations. Prior to study initiation, the protocol, informed consent and other relevant documentation were reviewed and approved by institutional review boards (IRB)/ethics committees (EC) (Advarra, Aurora, ON, Canada [approval dates 22 October 2021 and 5 November 2021] for two sites in Quebec, Canada and the single site in Ontario, Canada; CHUM (Centre hospitalier de l’Université de Montréal), Montreal, QC, Canada [approval date 21 June 2022] for the third site in Quebec, Canada; Health and Disability Ethics Committees, Wellington, New Zealand [approval date 10 March 2022] for the single site in New Zealand; Zugume Comite De Etica Independiente, Guatemala, Guatemala [approval date 20 October 2021] for the single site in Honduras; and the Armenian Ministry of Health, Yerevan, Armenia [approval date 26 September 2022] for the single site in Armenia). Prospective informed consent was obtained of all participants. The trial was registered with the National Library of Medicine (ClinicalTrials.gov, NCT05127551).
Participants
Main inclusion criteria included participants between 35 and 85 years of age diagnosed with primary open-angle glaucoma (POAG), pseudoexfoliative glaucoma or pigmentary glaucoma, with screening IOP ≤ 24 mmHg on 0–3 IOP-lowering medications, and unmedicated baseline mean diurnal IOP (MDIOP) ≥ 21 mmHg and ≤ 36 mmHg following a medication washout period. Eyes were required to have an open angle (Shaffer grade ≥ 3 via gonioscopic assessment) and corrected visual acuity of 20/80 Snellen or better.
Key exclusion criteria included OAG secondary to elevated episcleral venous pressure, traumatic glaucoma, angle recession glaucoma, uveitic glaucoma, neovascular glaucoma; angle closure glaucoma and glaucoma associated with vascular disorders; selective laser trabeculoplasty (SLT), peripheral laser iridotomy or cataract surgery within 90 days prior to screening; peripheral anterior synechiae (PAS) extending more than 6 clock hours that interfered with visualization of the target implant location or proper surgical implantation; argon laser trabeculoplasty or other glaucoma surgery of any type, and any other prior intraocular or extraocular surgeries known to affect IOP; chronic ocular inflammatory disease or presence of active ocular inflammation/infection. There were no criteria limiting glaucoma disease severity.
Study Devices
The iStent infinite® Trabecular Micro-Bypass System Model iS3 is a current product that contains three preloaded intraocular stents manufactured from implant grade titanium. Each of the three stents is 360 µm in diameter and height with a central inlet and outlet lumen of 80 µm in diameter. The three stents, implanted approximately 2 clock hours from each other in the trabecular meshwork, occupy an approximate 3% of the angle, thereby leaving approximately 97% of angle tissue untouched. As implanted, the three stents provide for aqueous outflow by accessing up to 240° of collector channels [11]. The iStent infinite is commercially available in the USA for use as a standalone procedure in patients with POAG in whom previous medical and surgical treatment has failed, and in Canada and Australia for standalone and combination cataract surgery and in several other countries. Previous work has summarized the safety and effectiveness from the iStent infinite pivotal trial [12].
The Hydrus Microstent is a crescent-shaped implantable stent, cut from nitinol tubing, and pre-loaded onto a hand-held delivery system. The overall length is approximately 8 mm with major and minor axes of 292 µm and 185 µm, respectively [13].The stent length and curvature occupy approximately 3 clock hours of Schlemm’s canal with the proximal portion of the implant exiting the canal through the trabecular meshwork. The Hydrus Microstent is commercially available in the USA for use in conjunction with cataract surgery for the reduction of IOP in adult patients with mild to moderate POAG. Previous work has summarized the safety and effectiveness from the Hydrus pivotal trial [14].
Figure 1 shows the size of both devices compared to a penny, and Table 1 provides dimensions of the iStent infinite and the Hydrus devices.
Fig. 1
iStent infinite trabecular micro-bypass stent and Hydrus Microstent compared to a penny
360 μm width of flange (portion resting on trabecular meshwork)
292 μm width of inlet
(major axis dimension)
Length residing in anterior chamber
105 μm
Est. 1000 μm
Procedures and Visits
At the start of the screening visit and prior to study-specific tests, subjects underwent the informed consent process. At this screening visit, demographic data, medical/ocular history, and concomitant medication information were collected. Screening assessments included corrected visual acuity (Snellen), perimetry, slit-lamp biomicroscopy, single timepoint IOP via Goldmann tonometry, gonioscopy, pachymetry, and dilated ophthalmoscopy. In addition, women of childbearing potential underwent a pregnancy test. Subjects who met eligibility criteria were instructed to start IOP-lowering medication washout in one or both potential qualifying eyes and to return for a baseline visit to measure unmedicated MDIOP. The duration of medication washout was 5 days for carbonic anhydrase inhibitors and miotics; 2 weeks for alpha agonists; and 4 weeks for beta blockers, prostaglandin analogues, and rho-kinase inhibitors. At the baseline visit, subjects’ medical/ocular history and concomitant medications status were updated. For each qualifying eye, occurrence of adverse events (AEs) was noted, and manifest refraction and best spectacle-corrected visual acuity (BSCVA; via Early Treatment Diabetic Retinopathy Study, ETDRS) were assessed, and IOP via Goldmann tonometry was measured at 8 A.M., 12 P.M., and 4 P.M. At that visit, unmedicated MDIOP (the average of the 8 A.M., 12 P.M., and 4 P.M. IOPs) was required to be ≥ 21 mmHg and ≤ 36 mmHg.
If only one eye of a subject met all eligibility criteria, that eye was then randomized. If both eyes qualified but had different lens status (i.e., one eye phakic, one eye pseudophakic), only one eye, chosen by the investigator, was to be randomized into the study. If both eyes of the subject qualified and had the same lens status then the investigator was to determine the first eye to be treated by selecting the worst of the two eyes based on visual acuity, optic nerve appearance, IOP, or other glaucoma-related variables. If the eyes were equivalent, the left eye was to be randomized and treated first according to a randomization schedule to undergo implantation with either iStent infinite or Hydrus. The contralateral eye was to receive the opposite treatment the following day or at a later time.
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Following completion of the baseline visit, eligible subjects were scheduled for surgery and instructed to follow a preoperative regimen according to the investigator’s standard of care for MIGS procedures. Surgery was performed according to the manufacturer’s instruction for use for the applicable study device [15, 16]. Following surgery, subjects were instructed to use topical antibiotic (fluoroquinolone or alternate, if contraindicated) eye drops four times daily for 1 week and topical non-steroidal anti-inflammatory eye drops for 1 week.
Study visits were scheduled to occur at postoperative day 1, week 1, and months 1, 3, 5, and 6. In order to obtain unmedicated MDIOP at month 6, eyes on IOP-lowering medication at month 5 initiated a washout prior to month 6 according to the previously described washout times by medication class, if safe. Eyes on no IOP-lowering medication at month 5 returned for an unmedicated MDIOP measurement at month 6.
A single timepoint IOP was measured on postoperative day 1, week 1, and months 1, 3, and 5, within ± 1 h of the time of day measured at screening. After removal and washout of IOP-lowering medications, diurnal (8 A.M., 12 P.M., and 4 P.M.) IOP was measured at month 6. IOP measurements (diurnal and single timepoint IOP) used the standard two-person method common in glaucoma studies [17].
Additional assessments at all visits included medication and adverse event assessment, slit-lamp biomicroscopy, and visual acuity (pinhole at day 1 and week 1; corrected at months 1, 3, and 5, and BSCVA at month 6). At selected visits, the following additional assessments were performed: gonioscopy at day 1, week 1, and months 1, 3, and 6; pachymetry at day 1 and week 1, ophthalmoscopy at months 1, 3, and 6; and perimetry at month 6. Investigators used their clinical judgment on a case-by-case basis regarding if and when to administer IOP-lowering medications. The protocol instructed investigators to attempt to use the same IOP-lowering medication(s) or class(es) of medication(s) that the subject was using prior to surgery.
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Effectiveness and Safety Outcome Measures at Month 6
Analyses were performed when all study eyes had completed the month 6 visit or had prematurely exited before 6 months. An observed case analysis assessed the proportion of eyes at month 6 achieving MDIOP reduction from baseline of ≥ 20% regardless of IOP-lowering medication or surgical complications. In addition, a prespecified primary effectiveness analysis assessed the proportion of eyes at month 6 achieving an unmedicated MDIOP reduction from baseline of ≥ 20% without surgical complications (e.g., improper stent placement, failed stent implantation, peripheral anterior synechiae (PAS) > 1.0 mm, or IOP-related secondary surgical interventions; see Table 6 for a complete list of surgical complications). Eyes with surgical complications, or with missing data due to premature study exit as a result of surgical complications, or on IOP-lowering medications were imputed as failures. For eyes with missing data without premature study exit or due to premature study exit for reasons other than surgical complications, data were imputed using multiple imputation methodology, assuming the data were missing at random.
Additional effectiveness outcome analyses included an observed case analysis of the proportion of eyes without any exclusions (i.e., regardless of medication use or surgical complications) achieving MDIOP ≤ 17 mmHg as well as an analysis of the proportion of eyes at month 6 achieving a washed out MDIOP ≤ 17 mmHg without surgical complications or IOP-related secondary surgical interventions.
As another set of secondary effectiveness outcomes, we also analyzed the change from baseline in MDIOP at month 6. The observed case analysis, which included all eyes having IOP data at the month 6 study endpoint without any exclusions, was performed to assess the change from baseline in MDIOP. In another pre-specified version of this effectiveness analysis, changes from baseline MDIOP month 6 data were imputed using the worst observation carried forward (a conservative analysis defined as the maximum IOP at baseline or at any other postoperative visit) for eyes with surgical complications, or with missing data due to premature study exit as a result of surgical complications, or for eyes on IOP-lowering medications. For eyes with missing data without premature study exit or due to premature study exit for reasons other than surgical complications, data were imputed using multiple imputation methodology, assuming the data were missing at random.
For eyes with unmedicated IOP and without surgical complications, the distribution of IOP and IOP percent change from baseline were summarized by visit for each treatment arm. The mean IOP at each visit was summarized as a continuous variable for each treatment arm. Finally, the mean number of IOP-lowering medications at each visit was assessed (observed case methodology was used).
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Safety parameters included intraoperative and postoperative complications, corrected visual acuity, findings from slit-lamp biomicroscopy, ophthalmoscopy, gonioscopy, perimetry, and adverse events. All surgical complications were reported as adverse events.
Statistical Analysis
The study was designed to detect a 25% difference between the two treatment groups in percentage of implanted eyes achieving an unmedicated MDIOP reduction from baseline of ≥ 20% at month 12 without surgical complications, assuming independence between eyes for those subjects with both eyes enrolled. With a two-sided alpha of 0.049 at month 12 (to account for the analysis at month 6) and 80% power, 67 study eyes implanted with each treatment were required. Assuming a premature discontinuation rate of 10% at month 12, 150 study eyes overall (75 per treatment group) were required to be implanted.
A generalized estimating equation model, including treatment as a fixed effect and subject as a repeated effect to account for the correlation (assuming a compound symmetric covariance structure) between eyes within a subject (for subjects with both eyes implanted), was used to test for differences between treatments in dichotomous effectiveness endpoints using two-sided p values and confidence intervals (CI). The intent-to-treat (ITT) analysis set consisted of all eyes that were randomized. Effectiveness analyses were performed on the ITT analysis set. The safety analysis set consisted of all eyes in which the treatment procedure was initiated. Safety outcomes were performed using the safety analysis set. In general, continuous measures were summarized with descriptive summary statistics including the number of observations, mean, and SD. Two-sided 95% CI were reported. Categorical measures were summarized with percentage and number of cases. Unless otherwise specified p values are two-sided.
For the testing of between treatment group demographic and preoperative characteristics, two-sample t tests were used for continuous measures and Pearson chi-squared tests were used to assess categorical measures. For categorical analysis with small expected cell values, Fisher’s exact test was used.
Statistical analyses were performed using SAS (Statistical Analysis Software, SAS Institute, Inc., Cary, North Carolina, US) version 9.4 or higher.
Results
Disposition
A total of 144 subjects were screened for the study eligibility of one or both eyes, of which 37 subjects (25.7%) failed screening or baseline eligibility criteria. Of the 107 eligible subjects randomized, 18 subjects were randomized to iStent infinite implantation in one eye, 16 subjects were randomized to Hydrus in one eye, and 73 subjects were randomized to iStent infinite in one eye and Hydrus in the contralateral eye. This approach resulted in 91 eyes randomized to iStent infinite and 89 eyes to Hydrus stent implantation.
By the month 6 visit, one subject who had been implanted with iStent infinite in one eye and Hydrus in the contralateral eye had withdrawn consent and was discontinued from the study. In addition, two unilaterally implanted subjects in the iStent infinite group and one unilaterally implanted subject in the Hydrus group missed the month 6 visit. Therefore, 88 (96.7%) eyes in the iStent infinite group and 87 eyes (97.8%) in the Hydrus group were available for analysis at the month 6 visit.
Demographics and Preoperative Characteristics
Demographics and preoperative characteristics are provided in Tables 2 and 3, respectively. Eyes were well matched for demographics and preoperative characteristics; and sex and ethnicity characteristics were considered representative of the general population of patients with glaucoma. In the ITT population the mean ± SD age was 63.0 ± 10.7 years in the iStent infinite group and 62.9 ± 10.6 years in the Hydrus group. The majority of eyes had POAG (96.7% iStent infinite eyes and 94.4% Hydrus eyes), had mild-to-moderate OAG (95.5% iStent infinite eyes and 96.6% Hydrus eyes), and were phakic (65.9% iStent infinite eyes and 64% Hydrus eyes). Mean IOP at screening was 17.0 ± 3.2 mmHg while on 1.6 ± 0.9 medications, and baseline unmedicated MDIOP was 23.7 ± 2.9 mmHg in the iStent infinite group. In the Hydrus group, mean IOP at screening was 17.1 ± 3.3 mmHg while on 1.5 ± 0.9 medications, and baseline unmedicated MDIOP was 23.5 ± 2.7 mmHg.
Table 2
Demographics (intent-to-treat population)
Parameter
iStent infinite
N = 91
Hydrus
N = 89
P value
Age
Mean (SD) age, years
63.0 (10.7)
62.9 (10.6)
0.9499
Sex
Female, n (%)
57 (62.6)
57 (64.0)
0.8447
Race
White, n (%)
90 (98.9)
87 (97.8)
0.7458
Asian, n (%)
1 (1.1)
1 (1.1)
Black/African American, n (%)
0
1 (1.1)
Ethnicity
Hispanic or Latino, n (%)
28 (30.8)
25 (28.1)
0.6934
Not Hispanic or Latino, n (%)
63 (69.2)
64 (71.9)
SD standard deviation
Table 3
Preoperative characteristics
Parameter
iStent infinite
N = 91
Hydrus
N = 89
P value
Glaucoma status
Primary open-angle glaucoma, n (%)
88 (96.7)
84 (94.4)
0.6392
Pseudoexfoliative glaucoma, n (%)
1 (1.1)
2 (2.2)
Pigmentary glaucoma, n (%)
2 (2.2)
3 (3.4)
Ocular status
One eye, n (%)
18 (19.8)
16 (18.0)
0.7574
Both eyes, n (%)
73 (80.2)
73 (82.0)
Phakic, n (%)
60 (65.9)
57 (64.0)
0.7905
Pseudophakic, n (%)
31 (34.1)
32 (36.0)
BSCVA; Snellen equivalent of mean logMAR
20/23
20/23
0.8795
Visual field, mean deviation (dB), mean (SD)
− 5.90 (5.99)
− 5.91 (5.90)
0.9919
Visual field, mean deviation (dB)
≥ − 12 dB
77/89 (86.5%)
76/88 (86.4%)
< − 12 dB to − 20 dB
8/89 (9.0%)
9/88 (10.2%)
< − 20 dB
4/89 (4.5%)
3/88 (3.4%)
Missing
2
1
Prior SLT, n (%)
22 (24.2)
20 (22.5)
0.7870
Screening medicated IOP
IOP (mmHg), mean (SD)
17.0 (3.2)
17.1 (3.3)
0.9018
Number of medication classes at screening
Number, mean (SD)
1.6 (0.87)
1.5 (0.87)
0.4417
0
6/91 (6.6%)
7/89 (7.9%)
0.9698
1
45/91 (49.5%)
43/89 (48.3%)
2
23/91 (25.3%)
24/89 (27.0%)
3
17/91 (18.7%)
15/89 (16.9%)
Unmedicated diurnal IOP at baseline
IOP (mmHg), mean (SD)
23.7 (2.9)
23.5 (2.7)
0.5648
BSCVA best spectacle-corrected visual acuity, dB decibels, IOP intraocular pressure, logMAR logarithm of the minimum angle of resolution, SD standard deviation, SLT selective laser trabeculoplasty
Operative Results
Ninety of 91 eyes (98.9%) in the iStent infinite group were implanted with three stents. In one eye, a fourth stent was implanted as a result of one of the stents having been implanted below the scleral spur. This was reported as an adverse event of “improper anatomical placement” and categorized as a surgical complication. In one iStent infinite eye, the insertion device damaged the anterior capsule resulting in cataract formation, requiring cataract surgery the following day. At 6 months postoperatively, PAS > 1 mm was reported as an adverse event and surgical complication in this eye.
In the Hydrus group, 88 of 89 eyes (98.9%) were implanted with stents. One eye did not receive a stent despite three attempts of placement, positioning in the supraciliary space and iris prolapse that required an intraoperative iridotomy. On the basis of these complications, the surgeon decided to abort implantation, and intraoperative adverse events and surgical complication of “failure to implant stent” and “iris prolapse” were reported. The failed implantation also resulted in two postoperative adverse events—PAS, 5 days after surgery and dyscoria, 3 weeks after surgery. One pseudophakic Hydrus eye experienced vitreous prolapse due to significant capsular tear/rupture requiring vitrectomy during the surgical procedure.
Seven additional Hydrus eyes (7.9%) were reported to have adverse events and surgical complication of improper anatomical placement. In one eye, complicated by iridodialysis and inadvertent iridectomy during implantation, the stent was noted to be inadvertently placed in the suprachoroidal space. This subject developed postoperative PAS at month 6. In three eyes a portion of the stent was noted to be in the suprachoroidal space. In a fifth eye the surgeon noted the distal tip to be posterior to Schlemm’s canal and the anterior tip “slightly further into the anterior chamber than ideal”. In a sixth eye the stent was placed with the distal end protruding into the anterior chamber, and in the seventh eye the stent was implanted with the distal end contacting the iris.
Primary Effectiveness Outcomes at Month 6
The observed case analysis of the proportion of eyes with month 6 MDIOP reduction from baseline of ≥ 20% regardless of medication use or surgical complications showed that a numerically similar proportion of 82.7% of eyes in the iStent infinite group compared to 78.9% of eyes in the Hydrus group achieved treatment success (difference 3.9%, 95% CI − 4.8%, 12.5%; Fig. 2a).
Fig. 2
a Observed case analysis: the proportion of eyes that achieved mean diurnal IOP reduction from baseline ≥ 20% at month 6 regardless of surgical complications or IOP-lowering medications. b Predefined primary effectiveness analysis: the proportion of eyes with no surgical complications that achieved unmedicated mean diurnal IOP reduction from baseline of ≥ 20% at month 6. CI confidence interval, IOP intraocular pressure. Error bars represent upper 95% confidence intervals
At month 6, the prespecified primary effectiveness analysis was based on a responder analysis defined as the proportion of eyes with no surgical complications (as defined previously) that achieved an unmedicated MDIOP reduction from baseline of ≥ 20%. In this primary effectiveness analysis, 78.2% of eyes in the iStent infinite group compared to 65.0% of eyes in the Hydrus group achieved treatment success. On the basis of this primary analysis, which imputed eyes on IOP-lowering medications or that had surgical complications as failures (Table 4), the 13.2% treatment effect was statistically significant showing superiority of iStent infinite over Hydrus (95% CI 3.0%, 23.3%; P = 0.0111; Fig. 2b). Only three eyes in each group were on IOP-lowering medications, with the overall washout success rate of > 96% for both treatment groups.
Table 4
Eyes imputed as treatment failures at month 6
iStent infinite
N = 91
n (%)
Hydrus
N = 89
n (%)
Total eyes imputed as treatment failuresa
20 (22.0%)
32 (36.0%)
Eyes imputed as treatment failures due to 6-month unmedicated MDIOP reduction from baseline < 20%
15 (16.5%)
17 (19.1%)
Eyes imputed as treatment failures for reasons other than IOP reductionb
5 (5.5%)
15 (16.9%)
Study eye adverse event
0
0
Failure to washout IOP-lowering medications
3 (3.3%)
3 (3.4%)
Surgical complication
2 (2.2%)
13 (14.6%)
IOP-related secondary surgical intervention (SSI)
1 (1.1%)
2 (2.2%)
n number of eyes with the corresponding responses. % = 100 × (n/N)
IOP intraocular pressure, MDIOP mean diurnal intraocular pressure
aAn eye could be imputed as a treatment failure for more than one reason
bEyes were included in the primary category of “Eyes imputed as treatment failures for reasons other than IOP reduction”
Secondary Effectiveness Outcomes at Month 6
The proportion of eyes in the observed case analysis that achieved MDIOP of ≤ 17 mmHg at month 6 was 65.8% in the iStent infinite group compared to 64.2% in the Hydrus group (difference 1.5%; 95% CI − 8.7%, 11.7%) (Fig. 3a). The proportion of eyes with no surgical complications that achieved unmedicated MDIOP of ≤ 17 mmHg at month 6 was 62.0% in the iStent infinite group compared to 51.7% in the Hydrus group (difference 10.3%; 95% CI − 0.1%, 20.7%; P = 0.053) (Fig. 3b).
Fig. 3
a Observed case analysis: the proportion of eyes that achieved mean diurnal IOP ≤ 17 mmHg at month 6 regardless of surgical complications or IOP-lowering medications. b Predefined secondary effectiveness analysis: the proportion of eyes without surgical complications that achieved unmedicated mean diurnal IOP ≤ 17 mmHg at month 6. CI confidence interval, IOP intraocular pressure. Error bars represent upper 95% confidence intervals
In another observed case analysis, the mean change from baseline in MDIOP was − 7.4 ± 2.9 mmHg in the iStent infinite group and − 7.2 ± 2.9 mmHg in the Hydrus group. The difference between groups was − 0.2 mmHg (95% CI − 0.7 mmHg, 0.3 mmHg; P = 0.4732) (Fig. 4a). As shown in Fig. 4b, the mean change from baseline in month 6 unmedicated MDIOP was − 6.8 ± 4.1 mmHg in the iStent infinite group and − 5.7 ± 4.1 mmHg in the Hydrus group with data imputed for eyes on IOP-lowering medications, or with surgical complications. This -1.1-mmHg difference in mean change from baseline at month 6 was statistically significant and superior in the iStent infinite group versus the Hydrus group (95% CI − 2.0 mmHg, − 0.2 mmHg; P = 0.0147).
Fig. 4
a Observed case analysis: the change from baseline mean diurnal IOP at month 6 regardless of surgical complications or IOP-lowering medications. b Predefined secondary effectiveness analysis: the change from baseline in unmedicated mean diurnal IOP in eyes with no surgical complications at month 6. CI confidence interval, IOP intraocular pressure. Error bars represent upper 95% confidence intervals
The proportion of eyes with available IOP data and without surgical complications that achieved an unmedicated MDIOP of ≤ 21 mmHg was significantly greater in the iStent infinite group (89.8%) compared to the Hydrus group (75.9%) (P = 0.0146). Results for MDIOP ≤ 15 mmHg, ≤ 18 mmHg, and ≤ 21 mmHg are displayed in Fig. 5 (the results for MDIOP ≤ 15 mmHg and ≤ 18 mmHg were not statistically significant).
Fig. 5
Predefined secondary effectiveness analysis: the proportion of eyes with available IOP data and without IOP-lowering medications or surgical complications, and with mean diurnal IOP ≤ 15 mmHg, ≤ 18 mmHg, and ≤ 21 mmHg at month 6. IOP intraocular pressure
Figure 6 shows the proportion of eyes with available IOP data and without surgical complications having a reduction from baseline in unmedicated MDIOP of ≥ 40%, ≥ 30%, and ≥ 20% at month 6. The proportion of eyes with ≥ 20% reduction was significantly greater in the iStent infinite group (77.3%) compared to the Hydrus group (63.2%) (P = 0.0419).
Fig. 6
Predefined secondary effectiveness analysis: the proportion of eyes with available IOP data and without IOP-lowering medications or surgical complications, and with mean diurnal IOP reduction ≥ 40%, ≥ 30%, and ≥ 20% at month 6. IOP intraocular pressure
The observed case analysis of MDIOP was similar at month 6 in the iStent infinite (16.4 ± 3.3 mmHg; change from baseline − 7.4 ± 2.9 mmHg) and Hydrus (16.5 ± 3.2 mmHg; change from baseline − 7.2 ± 2.9 mmHg) groups. The unmedicated MDIOP for eyes without surgical complications was also similar in the iStent infinite (16.3 ± 3.4 mmHg) and Hydrus (16.5 ± 3.3 mmHg) groups. Notably at month 6, the mean number of IOP-lowering medications was 0.0 ± 0.18 in the iStent infinite group and 0.0 ± 0.26 in the Hydrus group, as three eyes in each group were on IOP-lowering medications. Both groups demonstrated a similar reduction in medication use over time (Fig. 7).
Fig. 7
Mean number of IOP-lowering medications by visit. Error bars represent 95% confidence intervals. The n values represent eyes available for analysis plus subjects who missed the visit but for whom medication data were available. IOP intraocular pressure
The overall number of ocular adverse events was lower in the iStent infinite group (22 reports per 91 subjects; 24.2%) compared to the Hydrus group (32 reports in 89 subjects; 36.0%) resulting in a difference in proportions of 11.8% (95% CI − 30.4%, 6.8%) (Table 5). The adverse events occurring with greater than 3% frequency were peripheral anterior synechia (4.4%) and iris atrophy (3.3%) in the iStent infinite group; and peripheral anterior synechia (10.1%), improper anatomical placement (7.9%), peripheral anterior synechia > 1 mm (4.5%), and significant hyphema (4.5%) in the Hydrus group. There were statistically significantly fewer improper anatomical placements in the iStent infinite group (1.1%) versus Hydrus group (7.9%) (difference 6.8%; 95% CI − 12.8%, − 0.8%). The differences between groups for other adverse events were not statistically significant.
IOP increase requiring management with oral medication
0
1 (1.1%)
− 1.1% (− 3.3%, 1.1%)
Improper anatomical placement
1 (1.1%)
7 (7.9%)
− 6.8% (− 12.8%, − 0.8%)
Iridodialysis and iridectomy
0
1 (1.1%)
− 1.1% (− 3.3%, 1.1%)
Iris atrophy
3 (3.3%)
1 (1.1%)
2.2% (− 2.2%, 6.5%)
Iris prolapse
0
1 (1.1%)
− 1.1% (− 3.3%, 1.1%)
Peripheral anterior synechiae
4 (4.4%)
9 (10.1%)
− 5.7% (− 13.3%, 1.9%)
Peripheral anterior synechiae > 1 mm
1 (1.1%)
4 (4.5%)
− 3.4% (− 8.2%, 1.4%)
Posterior vitreous detachment
0
1 (1.1%)
− 1.1% (− 3.3%, 1.1%)
Punctate staining*
1 (1.1%)
0
1.1% (− 1.1%, 3.3%)
Retained viscoelastic
1 (1.1%)
0
1.1% (− 1.1%, 3.3%)
Retinal detachment
0
0
NA
Significant hyphema
1 (1.1%)
4 (4.5%)
− 3.4% (− 8.2%, 1.4%)
Vitreous prolapse due to significant capsular tear/rupture
0
1 (1.1%)
− 1.1% (− 3.3%, 1.1%)
Worsening of preoperative meibomian gland dysfunction
1 (1.1%)
0
1.1% (− 1.1%, 3.3%)
BSCVA best spectacle-corrected visual acuity, CI confidence interval, IOP intraocular pressure, NA not applicable
*Linear staining secondary to tree branch injury
The proportion with surgical complications in the iStent infinite group was 3.3% (n = 3) compared to 16.9% (n = 15) in the Hydrus group. The 13.6% difference in proportions was statistically significantly lower in the iStent infinite group compared to the Hydrus group (95% CI − 23.8%, − 3.4%) (Table 6).
Table 6
Surgical complications through month 6
Surgical complications
iStent infinite
N = 91, n (%)
Hydrus
N = 89, n (%)
Difference in %
95% CI
Overall
3 (3.3%)
15 (16.9%)
− 13.6% (− 23.8%, − 3.4%)
Damage to crystalline lens
1 (1.1%)
0
1.1% (− 1.1%, 3.3%)
Failure to implant stent
0
1 (1.1%)
− 1.1% (− 3.3%, 1.1%)
Improper anatomical placement
1 (1.1%)
7 (7.9%)
− 6.8% (− 12.8%, − 0.8%)
Iridodialysis and iridectomy
0
1 (1.1%)
− 1.1% (− 3.3%, 1.1%)
Iris prolapse
0
1 (1.1%)
− 1.1% (− 3.3%, 1.1%)
Peripheral anterior synechiae > 1 mm
1 (1.1%)
4 (4.5%)
− 3.4% (− 8.2%, 1.4%)
Vitreous prolapse due to significant capsular tear/rupture
0
1 (1.1%)
− 1.1% (− 3.3%, 1.1%)
CI confidence interval
Other Safety Parameters
At month 6, 87.5% of iStent infinite eyes and 86.2% of Hydrus eyes had a BSCVA of 20/25 or better, and 96.6% of iStent infinite eyes and 97.7% of Hydrus eyes had a BSCVA of 20/40 or better. There was no clinically meaningful change from preoperative BSCVA or between group difference at month 6.
There were no other remarkable findings in slit-lamp biomicroscopy, gonioscopy, ophthalmoscopy, or perimetry.
Discussion
The Integrity study was designed to produce high-quality evidence of the unmedicated IOP reduction and safety of two currently available trabecular bypass stent technologies for patients with OAG, namely iStent infinite and Hydrus. In this study consisting primarily of eyes with mild-to-moderate OAG, we assessed month 6 MDIOP reduction as observed case analyses, as well as analyses of unmedicated MDIOP without surgical complications based on a prespecified statistical analysis plan. The primary effectiveness outcome was prospectively declared as the proportion of eyes without surgical complications, demonstrating a reduction from baseline of ≥ 20% in unmedicated MDIOP. Similar methodologies based on dichotomous composite primary effectiveness endpoint methods, that consider eyes on medication and with critical surgical complications primarily based on filtering surgeries, also are routinely utilized by sponsors to obtain regulatory approval of products in this medical device category.
We chose a composite analysis including surgical complications as failures in addition to effectiveness outcomes. We chose these criteria as these findings can potentially lead to damage to collateral tissue and/or inflammation. This is a particularly important consideration as MIGS devices are typically used in early glaucoma. For a comprehensive characterization of device performance, it is helpful to assess postoperative IOP-lowering outcomes while also considering learning curve, surgical predictability, and the potential for postoperative adverse events. We also reported an observed case analysis, conducted regardless of IOP-lowering medication use or surgical complications, focusing primarily on effectiveness to provide multiple ways to evaluate the data from this study.
Participating investigators were highly trained MIGS surgeons who had extensive experience with both the iStent infinite and Hydrus stent technologies. This interim analysis provides an early assessment of postoperative IOP reduction, safety, and IOP-lowering medication use through month 6.
Month 6 effectiveness outcomes were favorable in both groups, with observed case analyses showing similarly high proportions in both groups achieving ≥ 20% reduction in MDIOP from baseline and MDIOP ≤ 17 mmHg. Further, in the observed case analyses, both groups demonstrated similar statistically and clinically significant MDIOP reduction from baseline of greater than 7 mmHg, with MDIOP below 17 mmHg for both the iStent infinite (change from baseline − 7.4 ± 2.9 mmHg) and Hydrus (change from baseline − 7.2 ± 2.9 mmHg) groups at month 6. Both iStent infinite and Hydrus eyes demonstrated a reduction in the need for IOP-lowering medication, with 0.0 ± 0.18 IOP-lowering medications for iStent infinite and 0.0 ± 0.26 for Hydrus at month 6, while maintaining effective IOP control.
While effectiveness outcomes were favorable and similar in both groups, when surgical complications were considered as failures, a clinically meaningful and statistically significantly superior proportion of iStent infinite eyes versus Hydrus eyes achieved an unmedicated MDIOP reduction of at least 20%. In this prospectively defined primary effectiveness analysis, 78.2% of iStent infinite eyes compared to 65% of Hydrus eyes achieved this level of IOP reduction at month 6. In the reduction from baseline in unmedicated MDIOP when incorporating surgical complications as failures, the iStent infinite group achieved a clinically meaningful [18, 19] and statistically significantly superior change from baseline in unmedicated MDIOP (− 6.8 mmHg) compared to the Hydrus group (− 5.7 mmHg). Furthermore, a significantly greater proportion of eyes in the iStent infinite group versus Hydrus group achieved an IOP of ≤ 21 mmHg for eyes not on IOP-lowering medications or without surgical complications.
With regards to safety, a numerically lower number of adverse events were reported in the iStent infinite group (22 reports per 91 subjects; 24.2%) compared to the Hydrus group (32 reports in 89 subjects; 36.0%).
A significantly higher rate of surgical complications was observed in the Hydrus group (16.9%) compared with the iStent infinite group (3.3%). This finding may be related to the substantial dimensional differences between the micro-invasive iStent infinite and the much larger Hydrus device. Separately, the iStent technology has shown a higher degree of safety related to the corneal endothelium compared to Hydrus with a phaco control group [20]. The difference in surgical complications in favor of iStent infinite contributed to the iStent’s superior outcomes in the primary effectiveness analysis compared to the observed case analysis. Safety is paramount with MIGS devices as they are often used earlier than traditional bleb surgery. Although there were no severe vision-threatening complications in either group up to 6 months, the potential for PAS progression and/or clinical sequelae from device malposition is an important consideration [14, 21]. Thus, in our trial we chose to include these findings as grounds for treatment failure. For a comprehensive characterization of device performance, it is critical to assess postoperative IOP-lowering outcomes of these two technologies while also considering surgical difficulty, and potential for postoperative management of related adverse event sequelae. However, we also have provided the results of an observed case analysis by including eyes with surgical complications and eyes on IOP-lowering medications to allow the reader to interpret this study in the way they feel is most “real world”.
The current Integrity study and the previously published Compare study are the only randomized, prospective trials evaluating standalone administration of these trabecular bypass stents. The Compare clinical trial compared the original iStent and the current Hydrus stents and reported greater effectiveness with Hydrus [5]. There are important differences between the Integrity study and the Compare study. The Compare study employed a 20-year-old technology—using two original first-generation iStent devices—while the current Integrity study used current generation iStent infinite stents and the current Hydrus stent, the latter of which is the original unchanged model also used in the Compare study. Limitations of this prior study included an inability to washout many eyes, subsequent elimination of terminal washout, and a change in the primary endpoint midway through the study thereby limiting the ability to fully scientifically evaluate device effectiveness [22, 23]. These limitations of the Compare study have been described previously [24].
The Integrity study is the largest prospective, randomized comparison of an iStent technology versus Hydrus. This study, which evaluated side-by-side the current iStent infinite and Hydrus models, provides robust evidence of superior effectiveness and safety of iStent infinite compared to Hydrus.
One limitation of the current study is that an algorithm for reintroduction of IOP-lowering medication was not defined in the protocol, other than the instruction for investigators to add the same IOP-lowering medications or classes of medications that the subject had used prior to surgery. However, this limitation is minimized as a result of the IOP-lowering medication washout requirement prior to the month 6 visit which was carried out with > 96% success in both groups. In addition, the study was not powered for the 6-month effectiveness evaluation; however, multiplicity adjustments have been incorporated for future month 12 and month 24 analyses to account for the current analysis. Another limitation may be the allowance for two eyes of the same subject to be randomized into the study. However, this prospectively designed feature was accounted for in the statistical model. Other limitations may be the relatively short follow-up (i.e., 6 months), lack of racial diversity, and the potential for regression to the mean since IOP was not measured on multiple days. However, the study remains ongoing with future analyses through 24 months to compare safety and IOP outcomes of these two trabecular bypass technologies.
Conclusion
This study produced high-quality evidence of the risks and benefits of iStent infinite versus Hydrus. This analysis of data from this prospective, randomized, multicenter study, compared IOP-lowering effectiveness of two different trabecular bypass stents (the current fourth-generation iStent infinite and current Hydrus stents) while taking into consideration IOP-lowering medication washout and surgical complications. In observed case effectiveness analyses, both devices demonstrated similar robust IOP-lowering. In the prospectively defined primary effectiveness analysis, the fourth-generation iStent infinite trabecular micro-bypass stents demonstrated a statistically significant superiority in IOP-lowering treatment effect when incorporating IOP-lowering medication use and surgical complications in a head-to-head comparison with the Hydrus trabecular stent through 6 months after implantation.
Medical Writing, Editorial, and Other Assistance
The authors acknowledge Kun Zheng of Glaukos Corporation for statistical programming and Sara Heedy, PhD of Glaukos Corporation for graphing the figures.
Authorship
Authorship of this manuscript is in accordance with the guidelines of the International Committee of Medical Journal Editors.
Declarations
Conflict of Interest
Iqbal Ike K. Ahmed has received consulting fees from Aequus, Ace Vision, Aerie Pharmaceuticals, Akorn, Alcon, Allergan, Aquea Health, Inc, ArcScan, Avellino Lab USA, Inc, Avisi, Bausch Health, Beaver Visitec, Beyeonics, Bionode, Carl Zeiss Meditec, Centricity Vision, Inc, CorNeat Vision, Custom Surgical, Elios Vision, ElutiMed, Equinox, eyeFlow, Inc, EyeMed, Exhaura Limited, Genentech, Glaukos, Gore, Heine, Heru, Iantrek, InjectSense, Iridex, iStar, Ivantis, Johnson & Johnson Vision, Labtician Thea, LayerBio, Leica Microsystems, LifeLong Vision, Long Bridge Medical, Inc, MicroOptx, MST Surgical, Myra Vision, New World Medical, NovaEye, Ocular Instruments, Ocular Therapeutix, Oculo, Oculus Surgical, Omega Ophthalmics, PolyActiva, PulseMedica, Radiance Therapeutics, Inc, Rheon Medical SA, Ripple Therapeutics, Sanoculis, Santen, Shifamed, LLC, Sight Sciences, Smartlens, Inc, Stroma, Thea Pharma, ViaLase, Visus Therapeutics, Vizzario, VSY Biotechnology, and Zilia, Inc; research grants/support from Aerie Pharmaceuticals, Alcon, Allergan, Bionode, Glaukos, iCare, Ivantis, Johnson & Johnson Vision, New World Medical, and Santen; and speaker honoraria from Alcon, Allergan, Carl Zeiss Meditec, Heine, Johnson & Johnson Vision, MST Surgical, and Singapore Biodesign Programme Office. John P. Berdahl has received consulting fees from Alcon, Bausch + Lomb, Elios Vision, Inc., Glaukos, Imprimis, Sight Sciences, ViaLase, Johnson & Johnson; lecture/honoraria support from Alcon, Bausch + Lomb, Glaukos, Imprimis, ViaLase; and research/grant support from Alcon, and Glaukos. Arkadiy Yadgarov has received consulting fees from AbbVie, Alcon, Bausch + Lomb, Glaukos, IanTrek, and Sight Sciences. George R. Reiss has received consulting fees from Alcon, Allergan/Abbvie, Elios, Glaukos, iStar Medical, New World Medical, Sanoculis, Spyglass, Radius XR and WL Gore & Associates. Steven R. Sarkisian Jr. has received financial support from Glaukos, AbbVie, Allysta Pharmaceuticals, Elios Vision, iStar Medical, Ocular Therapeutix, Sight Sciences, Inc., Bausch + Lomb, Carl Zeiss Meditec USA, Inc., Aerie Pharmaceuticals, Inc., TearLab Corp.; consulting fees from Glaukos, Alcon Laboratories, Inc., AbbVie, Bausch + Lomb, Beaver-Visitec International, Inc., Icare USA, Inc., Ocular Science, Sight Sciences, Inc.; lecture fees from Aerie Pharmaceuticals, Inc., Alcon Laboratories, Inc., AbbVie, Bausch + Lomb. Sébastien Gagné has received consulting fees from Alcon, Allergan/Abbvie, Glaukos, and Johnson and Johnson; research/grant support from Alcon, Allergan/Abbvie, Bayer, Clearside Biomedical, Glaukos, iStar, Johnson and Johnson, LightX Innovations, MicroOptx, Novartis, Roche, Sandoz, and Zilia; and owns stock/stock options in LightX innovations. Marco Robles has received research/grant support from Glaukos. Lilit A. Voskanyan has received research/grant support from Glaukos. Omar Sadruddin, Dari Parizadeh, Angela C. Kothe, Jane Ellen Giamporcaro, L. Jay Katz, and Tomas Navratil are employees of Glaukos Corporation and may have received stock and/or stock options.
Ethical Approval
Human subjects were included in this trial. The trial was undertaken in accordance with the tenets of the Declaration of Helsinki, and the protocol, consensus ethical principles derived from international guidelines and Council for International Organizations of Medical Sciences (CIOMS) International Ethical Guidelines, applicable ICH Good Clinical Practice (GCP) Guidelines, and applicable laws and regulations. Prior to study initiation, the protocol, informed consent and other relevant documentation were reviewed and approved by institutional review boards (IRB)/ethics committees (EC) (Advarra, Aurora, ON, Canada [approval dates 22 October 2021 and 5 November 2021] for two sites in Quebec, Canada and the single site in Ontario, Canada; CHUM (Centre hospitalier de l’Université de Montréal), Montreal, QC, Canada [approval date 21 June 2022] for the third site in Quebec, Canada; Health and Disability Ethics Committees, Wellington, New Zealand [approval date 10 March 2022] for the single site in New Zealand; Zugume Comite De Etica Independiente, Guatemala, Guatemala [approval date 20 October 2021] for the single site in Honduras; and the Armenian Ministry of Health, Yerevan, Armenia [approval date 26 September 2022] for the single site in Armenia). Prospective informed consent was obtained of all participants. The trial was registered with the National Library of Medicine (ClinicalTrials.gov, NCT05127551).
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Six-Month Outcomes from a Prospective, Randomized Study of iStent infinite Versus Hydrus in Open-Angle Glaucoma: The INTEGRITY Study
Verfasst von
Iqbal Ike K. Ahmed
John P. Berdahl
Arkadiy Yadgarov
George R. Reiss
Steven R. Sarkisian Jr.
Sébastien Gagné
Marco Robles
Lilit A. Voskanyan
Omar Sadruddin
Dari Parizadeh
Jane Ellen Giamporcaro
Angela C. Kothe
L. Jay Katz
Tomas Navratil
Radcliffe NM, Shah M, Samuelson TW. Challenging the “topical medications-first” approach to glaucoma: a treatment paradigm in evolution. Ophthalmol Ther. 2023;12:2823–39.CrossRefPubMedPubMedCentral
2.
Castro C, Marta A, Marques JH, et al. Ocular surface changes in primary open angle glaucoma patients treated with topical antihypertensive drugs. J Glaucoma. 2023;32(10):113–20.CrossRef
3.
Nordstrom BL, Friedman DS, Mozaffari E, Quigley HA, Walker AM. Persistence and adherence with topical glaucoma therapy. Am J Ophthalmol. 2005;140:598–606.CrossRefPubMed
4.
Lee GA, Porter AJ, Vincent RA, Makk J, Vincent SJ. Combined phacoemulsification and microinvasive glaucoma surgery in comparison to phacoemulsification alone for open angle glaucoma. Eye. 2020;34:312–8.CrossRefPubMed
5.
Ahmed IIK, Fea A, Au L, et al. on behalf of the COMPARE Investigators. A prospective randomized trial comparing Hydrus and iStent microinvasive glaucoma surgery implants for standalone treatment of open-angle glaucoma. The COMPARE study. Ophthalmol. 2020;127:52–61.CrossRef
6.
Holmes DP, Clement CI, Nguyen V, et al. Comparative study of 2-year outcomes for Hydrus or iStent inject microinvasive glaucoma surgery implants with cataract surgery. Clin Exp Ophthalmol. 2022;50:303–11.CrossRefPubMed
7.
Jablońska J, Lewczuk K, Rękas MT. Comparison of safety and efficacy of Hydrus and istent combined with phacoemulsification in open-angle glaucoma patients: 24-month follow-up. Int J Environ Res Public Health. 2023;20:4152. https://doi.org/10.3390/ijerph20054152.CrossRefPubMedPubMedCentral
8.
Chee WK, Yip VCH, Tecson IO, et al. Comparison of efficacy of combined phacoemulsification and iStent inject versus combined phacoemulsification and Hydrus microstent. Clin Ophthalmol. 2023;17:1151–9.CrossRefPubMedPubMedCentral
9.
Hu R, Guo D, Hong N, Xuan X, Wang X. Comparison of Hydrus and iStent microinvasive glaucoma surgery implants in combination with phacoemulsification for treatment of open-angle glaucoma: Systematic review and network meta-analysis. BMJ Open. 2022;15:12.
10.
Wagner IV, Ang B, Checo L, et al. Spotlight on Schlemm’s canal microstent injection in patients with glaucoma. Clin Ophthalmol. 2023;17:1557–64.CrossRefPubMedPubMedCentral
11.
Glaukos data on file.
12.
Sarkisian SR Jr, Grover DS, Gallardo MJ, et al. Effectiveness and safety of iStent infinite trabecular micro-bypass for uncontrolled glaucoma. J Glaucoma. 2023;32(1):9–18.
Samuelson TW, Chang DF, Marquis R, et al. A Schlemm canal microstent for intraocular pressure reduction in primary open-angle glaucoma and cataract: the HORIZON study. Ophthalmology. 2019;126(1):29–37.
Gordon MO, Beiser JA, Brandt JD, et al. The ocular hypertension treatment study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:714–20 (discussion 829–30).
18.
Leske MC, Heijl A, Hyman L, Bengtsson B, Dong L, Yang Z, EMGT Group. Predictors of long-term progression in the early manifest glaucoma trial. Ophthalmol. 2007;114(11):1965–72.
19.
Chauhan BC, Mikelberg FS, Balaszi AG, et al. Canadian Glaucoma Study: 2. risk factors for the progression of open-angle glaucoma. Arch Ophthalmol. 2008;126(8):1030–6. (Erratum in: Arch Ophthalmol. 2008;126(10):1364.)
20.
Ahmed IIK, Sheybani A, De Francesco T, et al. Long-term endothelial safety profile with iStent inject in patients with open-angle glaucoma. Am J Ophthalmol. 2023;252:17–25.CrossRefPubMed
21.
Sachdeva N, Sun LW, Young J, Chen A. Early to late explantation of Hydrus microstent MIGS device: a case series. Am J Ophthalmol Case Rep. 2024;36:102105.CrossRefPubMedPubMedCentral
Shaarawy TM, Sherwood MB, Grehn F, editors. World Glaucoma Association guidelines on design and reporting of glaucoma surgical trials. Amsterdam: Kugler; 2009.
24.
Khouri AS. Re: Ahmed et al.: A prospective randomized trial comparing Hydrus and iStent micro-invasive glaucoma surgery implants for standalone treatment of open-angle glaucoma: The COMPARE Study (Ophthalmol. 2020;127:52–61). Ophthalmol. 2020;127(4):e23-e24.
Je höher der BMI, umso höher ist das Risiko, bei einer Infektion zu sterben. Das gilt nicht nur für Covid-19, sondern für Infektionen allgemein. Bei einer Grad-III-Adipositas ist die Mortalität während einer Infektion sogar verdreifacht. Darauf deuten Daten aus Finnland und Großbritannien.
Periphere Fazialisparesen sollten nicht vorschnell als idiopathisch klassifiziert werden. Vor allem bei atypischen Manifestationen gilt es, auf dem Quivive zu sein. Der Fall einer 73-Jährigen zeigt, warum.
Bei der Festlegung der Intervalle für Kontrollkoloskopien nach einer Polypektomie sollten nicht ausschließlich polypenbezogene Merkmale berücksichtigt werden. Wie eine internationale Studie zeigt, beeinflussen auch individuelle demografische Faktoren, wie Geschlecht, Body-Mass-Index und Ethnie, das Rezidivrisiko.
In einer Kohortenstudie wurde ein Zusammenhang zwischen oralen Bakterien und Pilzen und dem Auftreten von Pankreaskarzinomen gesehen. Diese Assoziation könnte helfen, Patientinnen und Patienten für gezielte Vorsorgeuntersuchungen ausfindig zu machen.
