Key Points
Question
Is intraocular pressure (IOP) at 12 months following treatment with surgical peripheral iridectomy (SPI) with goniosynechialysis (GSL) and goniotomy (GT) noninferior to trabeculectomy in advanced primary angle-closure glaucoma (PACG) without cataract?
Findings
In this randomized clinical trial of 88 participants with advanced PACG without cataract, SPI + GSL + GT and trabeculectomy showed noninferior IOP differences at 12 months (noninferior margin: 4 mm Hg). The SPI + GSL + GT group had fewer postoperative interventions when including bleb massage, suture lysis, or releasable sutures, although no difference in numbers of antiglaucoma medication prescribed was detected.
Meaning
SPI + GSL + GT was noninferior to trabeculectomy for IOP control in patients with PACG without cataract at 12 months postoperatively, with fewer postoperative interventions.
Abstract
Importance
The safety and effectiveness of combining surgical peripheral iridectomy (SPI) with goniosynechialysis (GSL) and goniotomy (GT) vs trabeculectomy for intraocular pressure (IOP) reduction remains unknown.
Objective
To investigate the safety and effectiveness at 1 year of SPI + GSL + GT vs trabeculectomy in advanced primary angle-closure glaucoma (PACG) without cataract.
Design, Setting, and Participants
This noninferiority randomized clinical trial was conducted at 8 tertiary eye centers in China. A total of 88 Chinese patients (88 eyes) with advanced PACG without cataract were enrolled from January 2022 to July 2023. Data were analyzed from August 2024 to September 2024. Mean (SD) patient age was 60.3 (7.3) years, and 52 patients (59.1%) were female. Forty-three patients were randomized to SPI + GSL + GT and 45 were randomized to trabeculectomy; 86 patients (97.7%) completed the 12-month follow-up.
Interventions
Participants were randomized 1:1 to receive SPI + GSL + GT or trabeculectomy.
Main Outcomes and Measures
The primary outcome was IOP at 12 months (noninferior margin: 4 mm Hg). Secondary outcomes included surgical success (IOP: 5-18 mm Hg, ≥20% reduction from baseline, with or without antiglaucoma medications); postoperative complications and interventions, including bleb massage, suture lysis, or releasable sutures; and number of antiglaucomatous medications prescribed.
Results
At 12 months, the SPI + GSL + GT group had a mean (SD) IOP of 15.6 (4.0) mm Hg vs 14.9 (4.2) mm Hg in the trabeculectomy group (difference, 0.5 mm Hg; 95% CI, −1.2 to 2.2; P = .55), which was within the 4-mm Hg noninferiority margin. Qualified success rates were 38 of 43 participants (88.4%) for SPI + GSL + GT and 42 of 45 participants (93.3%) for trabeculectomy (difference, −5.0%; 95% CI, −19.6% to 8.5%; P = .48). However, complete success rates were lower in the SPI + GSL + GT group (26 participants [60.5%]) vs the trabeculectomy group (37 participants [82.2%]; difference, −21.8%; 95% CI, −40.2% to −2.4%; P = .03). Postoperative complications were present for 8 participants (18.6%) in the SPI + GSL + GT group vs 9 participants (20.0%) in the trabeculectomy group (difference, −1.4%; 95% CI, −17.9% to 15.1%; P = .71). Postoperative interventions were lower in the SPI + GSL + GT group (3 participants [7.0%] vs 25 participants [55.6%]; difference, 48.6%; 95% CI, 32.2%-65.0%; P < .001). Median (IQR) numbers of medications used decreased from 2 (0-3) to 0 (0-1) in the SPI + GSL + GT group and from 2 (2-3) to 0 (0-0) in the trabeculectomy group (difference, −0.81; 95% CI, −1.36 to −0.26; P = .004).
Conclusions and Relevance
In this randomized clinical trial among patients with advanced PACG without cataract, SPI + GSL + GT demonstrated noninferiority (4-mm Hg margin) to trabeculectomy for IOP at 12 months, with fewer interventions (including bleb massage, suture lysis, or releasable sutures) but no difference in postoperative medication use. This suggests SPI + GSL + GT as a potential alternative to trabeculectomy for similar cases, pending validation in larger sample sizes with smaller noninferiority margins.
Trial Registration
ClinicalTrials.gov Identifier: NCT05163951
This randomized clinical trial conducted at 8 tertiary eye centers in China investigates the safety and effectiveness at 1 year of surgical peripheral iridectomy with goniosynechialysis and goniotomy vs trabeculectomy in advanced primary angle-closure glaucoma (PACG) without cataract.
Introduction
Primary angle-closure glaucoma (PACG) is a prevalent form of glaucoma, accounting for 50% of glaucoma-related blindness worldwide.1,2 In 2020, PACG affected approximately 23.36 million individuals globally, and projections suggest that number will increase to 32.04 million by 2040, with an estimated 5.3 million of these individuals facing total vision loss.3 Most PACG cases occur in Asian populations, imposing a substantial impact on both families and society.3,4
Trabeculectomy is usually highly effective in managing PACG, particularly in its advanced stages.2,5,6,7 Nevertheless, potential complications like shallow anterior chamber, persistent hypotony, malignant glaucoma, endophthalmitis, bleb-related issues, and challenges in postoperative care can diminish its suitability.8,9 Combining surgical peripheral iridectomy (SPI) with postoperative antiglaucoma medications offers a promising alternative that may prevent these complications, especially in younger patients with shorter axial length or shallow anterior chambers.10 However, it is important to note that this approach necessitates ongoing use of antiglaucoma medications, which may not sufficiently and consistently control intraocular pressure (IOP) in all cases.
Growing evidence suggests that the combination of phacoemulsification and intraocular lens implantation (PEI), goniosynechialysis (GSL), and goniotomy (GT) is effective and safe for PACG with cataract.11,12,13,14,15,16,17 Our 2024 trial also confirmed that PEI + GSL + GT is as effective as phacotrabeculectomy in reducing IOP for advanced PACG with cataract over 1 year.17 However, lens removal in patients without cataract or with mild cataract remains controversial.18 A combination of SPI, GSL, and GT has been proven not only to effectively lower IOP, but also to address the challenges associated with trabeculectomy in advanced PACG without cataract.19,20 This regimen facilitates aqueous humor flow from the posterior to the anterior chamber through SPI, releases peripheral anterior synechiae (PAS) via GSL, and removes or incises trabecular meshwork (TM) through GT, thereby enhancing aqueous outflow and effectively lowering IOP.19,20,21 However, there has been no comparison between SPI + GSL + GT and trabeculectomy in terms of maintaining IOP and safety.
This randomized clinical trial aimed to assess the efficacy and safety of SPI + GSL + GT vs trabeculectomy for advanced PACG without cataract. As trabeculectomy is the criterion standard for IOP-lowering procedures in advanced PACG, the trial was structured as a noninferiority study. It was hypothesized that SPI + GSL + GT is noninferior to trabeculectomy in lowering IOP at 12 months postsurgery.
Methods
Trial Design and Participants
This multicenter, noninferiority randomized clinical trial (NCT05163951) was conducted across 8 large eye centers in China (Supplement 1).21 Participants with advanced chronic PACG were recruited after obtaining written informed consent and ensuring adherence to the Helsinki Declaration’s ethical standards. Ethics approvals were obtained for all sites, and participants were reimbursed for travel expenses. The trial protocol, including the steering committee and data safety and monitoring committee details, is available in Supplement 1.21 The trial adhered to the Consolidated Standards of Reporting Trials (CONSORT) reporting guidelines. Enrollment began on January 5, 2022, and was completed on July 12, 2023, and analysis started on August 1, 2024.
PACG was diagnosed with PAS more than 180° covering the nasal and inferior quadrants using a single-mirror gonioscope, along with significant glaucomatous optic neuropathy (cup-disc ratio ≥0.7, asymmetry >0.2, or rim width <0.1 vertical diameter at superotemporal and inferotemporal locations) and corresponding visual field (VF) defects on automated perimetry (Swedish Interactive Threshold Algorithm-Standard 24-2 program, Humphrey Field Analyzer 3-860 [Zeiss]).2,18 Advanced glaucoma was defined as having a mean deviation (MD) of −12 dB or fewer.18,22 Participants also needed to have no or mild cataract, with an uncorrected visual acuity (via Early Treatment Diabetic Retinopathy Study [ETDRS]) of 0.63 letter score or higher. One eye per participant was chosen for inclusion, prioritizing the eye with more severe VF or optic nerve damage if both were eligible.
Randomization and Masking
Following informed consent, participants were randomly assigned 1:1 to receive either SPI + GSL + GT or trabeculectomy. Although treatment assignments were known to both clinicians and participants, the process ensured impartial distribution. Enrollment was competitive, with each center striving diligently to recruit enough participants to fulfill the study requirements.
Surgical Procedures
Surgeries were performed under topical or general anesthesia, tailored to each participant’s health status. Senior ophthalmic surgeons (X. Zhang, S.F., L.T., L.L., L.X., G.T., H.Y., and X.N.) followed a standardized protocol.
In trabeculectomies, a fornix-based conjunctival flap was raised via an 11-o’clock to 1-o’clock corneal limbus incision, followed by lifting a 4 × 3–mm scleral flap. Mitomycin was applied for 1 to 5 minutes at concentrations of 0.2 to 0.5 mg/mL (Supplement 1).21 Participants aged 60 years and older were recommended to receive 0.4 mg/mL for 2 minutes, while those younger than 60 years received it for 3 minutes. Ultimately, 23 participants 60 years and older and 22 participants younger than 60 years received their designated doses. A 1 × 2–mm trabecular block was excised, followed by SPI over a 1.5 × 1.5–mm area. The scleral flap was repositioned and sutured using two 10-0 nylon stitches, and the conjunctiva was closed with 10-0 interrupted sutures (Video).
Video. Trabeculectomy and Surgical Peripheral Iridectomy With Goniosynechialysis and Goniotomy in PACG.
A, This video demonstrates the procedure of trabeculectomy for a patient with advanced primary angle-closure glaucoma (PACG) without cataract. A corneal limbus incision was made between the 11-o’clock and 1-o’clock positions to raise a fornix-based conjunctival flap. A scleral flap (4 × 3 mm; one-half thickness) was lifted and treated with mitomycin, 0.4 mg/mL, for 2 minutes underneath. Subsequently, a trabecular block measuring about 1 × 2 mm was excised followed by surgical peripheral iridectomy (SPI) over a 1.5 × 1.5-mm area. The scleral flap was then repositioned and sutured using two 10-0 nylon stitches and the bulbar conjunctiva closed with 10-0 interrupted sutures. B, This video demonstrates the procedure of SPI with goniosynechialysis (GSL) and goniotomy (GT) for a patient with advanced PACG without cataract. SPI was conducted initially in the superior-nasal quadrant. Subsequently, a 2.2-mm main corneal incision was made temporally. GSL was executed 120° using a chopper. A microhook (Tanito Microhook; Inami & Co) was inserted through the corneal incision, with the tip implanted into the Schlemm canal. This allowed for scratching and incising the inner walls of the Schlemm canal and the trabecular meshwork across a range of 120°.
In the SPI + GSL + GT procedure, SPI was conducted initially in the superior-nasal quadrant. Subsequently, GSL and GT procedures were performed either in the nasal quadrant from the temporal clear corneal incision or the inferior-nasal quadrant from the superior-temporal clear corneal incision.19,20 When performed in the nasal quadrant from the temporal corneal incision, a 2.2-mm main corneal incision was made temporally. GSL was executed over 120° using a chopper to effectively separate the PAS. Subsequently, a microhook (Tanito Micro Hook [Inami & Co]) was inserted through the corneal incision, with the tip implanted into the Schlemm canal to scratch and incise the inner walls of the Schlemm canal and the TM over 120° (Video). Further details are available in Supplement 1.
Patient Visits and Assessments
Follow-up visits were scheduled for 1 day, 1 week, and 1, 3, 6, and 12 months postsurgery. IOP was measured using Goldmann applanation tonometry, with a spike defined as 30 mm Hg or higher at any time postsurgery.23,24 Hyphema was identified by layered blood in the anterior chamber.13 The Tyndall effect was characterized by anterior chamber cells with a flare score of +2 or higher under high-powered magnification.25
Outcome Measures
The primary outcome was IOP at 12 months with or without medication. Secondary outcomes included surgical success rate21; postoperative complications and interventions, including bleb massage, suture lysis, or releasable sutures; and number of antiglaucomatous medications. Additional post hoc analyses assessed changes in best-corrected visual acuity (BCVA), degree of PAS, endothelial cell density (ECD), and VF. Surgical duration and costs were evaluated. Additionally, quality of life was assessed using the 5-level version of the EuroQol 5-dimension questionnaire (EQ-5D-5L) scale.26
Complete success was defined as postoperative IOP between 5 and 18 mm Hg with a 20% or higher reduction from baseline without medications. Qualified success was similar for IOP control but with the use of medications. Failure was marked by an IOP greater than 18 mm Hg, less than 20% reduction at 2 consecutive follow-up visits 3 months postoperation, an IOP less than 5 mm Hg at similar consecutive follow-up visits, the need for additional glaucoma surgery, or loss of light perception.6,7,27 Reoperations included any surgical intervention in the operating room, excluding procedures like bleb needling or laser suture lysis at the slitlamp.
Based on prior data showing average posttrabeculectomy IOP of 14 mm Hg,2,6,7,28 with success defined as an IOP of 18 mm Hg or less, and in line with a recent PACG randomized clinical trial comparing PEI + GSL vs PEI for IOP reduction,23 a 4-mm Hg noninferiority margin was set.
Sample Size Estimations
The sample size was based on the primary outcome. To achieve 90% power at a 1-sided 2.5% significance level with a noninferiority margin of 4 mm Hg and an SD of 5 mm Hg, 34 participants per group were needed. Accounting for a 20% dropout rate, 44 participants per group were enrolled, totaling 88 participants. The sample size was calculated using PASS software version 11.0 (NCSS).
Statistical Analysis
The normality of continuous variables was evaluated using the Shapiro-Wilk test and histograms, with data presented as means and SDs for normal distributions and frequencies with percentages for categorical variables. Primary and secondary outcomes were analyzed using an intention-to-treat (ITT) sample, including all randomized and treated participants. Primary outcomes were analyzed through linear regression, adjusted for baseline factors like age, sex, hypertension, and central corneal thickness (CCT). Missing data were handled via 10-fold multiple imputation. Least-squares mean differences and 95% confidence intervals were combined following the Rubin rules. Noninferiority was confirmed if the upper limit of the 95% confidence interval for IOP change was less than 4 mm Hg. Secondary outcomes were assessed using the Fisher exact test, with a best-case to worst-case approach for missing data. Per-protocol (PP) analyses were also conducted. Changes in BCVA, PAS, ECD, MD, and PSD of VF and EQ-5D-5L scores were analyzed using linear regression, adjusted for baseline values. All P values were 2-sided, and P < .05 for the primary outcome was considered statistically significant. No adjustment to P values for any subsequent analyses was undertaken. All statistical analyses were performed using Stata version 16 (StataCorp).
Results
Patient Recruitment and Baseline Characteristics
A total of 88 eyes from 88 participants with advanced PACG without cataract were analyzed for this study. The screening, recruitment, and flowchart of participants’ randomization are detailed in Figure 1. After 12 months, follow-up completion rates were 42 of 43 participants (97.6%) in the SPI + GSL + GT group and 44 of 45 participants (97.8%) in the trabeculectomy group. The demographic and ocular characteristics between the groups were comparable (Table 1).
Figure 1. Study Flowchart.
GSL indicates goniosynechialysis; GT, goniotomy; IOP, intraocular pressure; SPI, surgical peripheral iridectomy.
Table 1. Baseline Demographic and Ocular Characteristics.
| Characteristics | Mean (SD) | |
|---|---|---|
| SPI + GSL + GT (n = 43) | Trabeculectomy (n = 45) | |
| Age, y | 61.0 (7.0) | 59.8 (7.6) |
| Sex, No. (%) | ||
| Female | 26 (60.5) | 26 (57.8) |
| Male | 17 (39.5) | 19 (42.2) |
| BMIa | 24.8 (3.6) | 24.0 (3.4) |
| Diabetes, No. (%) | 4 (9.3) | 3 (6.7) |
| Hypertension, No. (%) | 9 (20.9) | 8 (17.8) |
| Blood pressure, mm Hg | ||
| Systolic | 131.7 (18.6) | 129.3 (18.4) |
| Diastolic | 79.1 (11.6) | 79.3 (13.1) |
| BCVA | ||
| LogMAR, median (IQR) | 0.0 (0.0 to 0.1) | 0.0 (0.0 to 0.1) |
| Snellen | 20/20 | 20/20 |
| IOP, mm Hg | 35.9 (9.1) | 38.0 (11.5) |
| Glaucoma medications, median (IQR), No. | 2 (0 to 3) | 2 (2 to 3) |
| Gonioscopy, median (IQR) | ||
| Mean Shaffer grade | 0.0 (0.0 to 1.0) | 0.0 (0.0 to 1.0) |
| PAS, clock hours | 10.0 (8.0 to 12.0) | 9.0 (8.0 to 12.0) |
| Axial length, mm | 22.6 (0.6) | 22.5 (0.7) |
| ACD, mm | 2.0 (0.3) | 2.1 (0.2) |
| CCT, μm | 543.7 (30.3) | 537.0 (30.7) |
| ECD, cells/mm2 | 2708.3 (282.6) | 2633.7 (383.6) |
| MD of VF, dB | −20.8 (7.6) | −20.9 (7.6) |
| PSD of VF, dB | 8.6 (2.6) | 8.9 (3.1) |
| EQ-5D-5L questionnaire score | 84.5 (8.9) | 86.6 (9.6) |
Abbreviations: ACD, anterior chamber depth; BCVA, best-corrected visual acuity; BMI, body mass index; CCT, central corneal thickness; ECD, endothelial cell density; EQ-5D-5L, 5-level version of the EuroQol 5-Dimension questionnaire; GSL, goniosynechialysis; GT, goniotomy; IOP, intraocular pressure; MD, mean deviation; PAS, peripheral anterior synechia; PSD, pattern standard deviation; SPI, surgical peripheral iridectomy; VF, visual field.
Calculated as weight in kilograms divided by height in meters squared.
Treatment Outcomes
Figure 2 shows IOP changes from baseline to 12 months postoperatively. The mean (SD) IOP in the SPI + GSL + GT group decreased from 35.9 (9.1) mm Hg to 15.6 (4.0) mm Hg (difference, −20.2 mm Hg; 95% CI, −23.3 to −17.1; P < .001) and the trabeculectomy group decreased from 38.0 (11.5) mm Hg to 14.9 (4.2) mm Hg (difference, −23.1 mm Hg; 95% CI, −26.4 to −19.8; P < .001). Both ITT and PP analyses revealed no differences in IOP at 12 months between the 2 groups (Table 2). Subgroup analysis confirmed no differences in 12-month IOP levels across treatment groups in 7 centers (eTable 1 in Supplement 2).
Figure 2. Mean Intraocular Pressure (IOP) Change Over the 12 Months of Follow-Up.
After 12 months, there was no difference in IOP between the 2 treatment groups (difference, 0.5 mm Hg; 95% CI, −1.2 to 2.2; P = .55). The P value was calculated using a linear regression model, adjusted for age, sex, hypertension, and central corneal thickness. GSL indicates goniosynechialysis; GT, goniotomy; SPI, surgical peripheral iridectomy.
Table 2. Intraocular Pressure (IOP) and Surgical Success Rates at 12 Months (Intention-to-Treat [ITT] Analysis and Per-Protocol [PP] Analysis).
| Characteristics | No. (%) | Group difference (95% CI) | P value | |
|---|---|---|---|---|
| SPI + GSL + GT | Trabeculectomy | |||
| ITT analysis | ||||
| IOP, No. | 43 | 45 | NA | NA |
| IOP at 12 mo, mean (SD), mm Hg | 15.6 (4.0) | 14.9 (4.2) | 0.5 (−1.2 to 2.2)a | .55a |
| Surgical success, No.b | 43 | 45 | NA | NA |
| Qualified success | 38 (88.4) | 42 (93.3) | −5.0 (−19.6 to 8.5) | .48c |
| Complete success | 26 (60.5) | 37 (82.2) | −21.8 (−40.2 to −2.4) | .03c |
| PP analysis | ||||
| IOP, No.d | 42 | 44 | NA | NA |
| IOP at 12 mo, mean (SD), mm Hg | 15.6 (3.9) | 14.8 (4.2) | 0.6 (−1.1 to 2.2)a | .52a |
| Surgical success, No.e | 43 | 44 | NA | NA |
| Qualified success | 38 (88.4) | 41 (93.2) | −4.8 (−19.1 to 8.8) | .48c |
| Complete success | 26 (60.5) | 36 (81.8) | −21.4 (−40.3 to −1.6) | .03c |
Abbreviations: GSL, goniosynechialysis; GT, goniotomy; NA, not applicable; SPI, surgical peripheral iridectomy.
Linear regression model with adjustment for age, sex, hypertension, and central corneal thickness was used to calculate 95% confidence intervals and P value.
In the ITT analysis, it was assumed that 1 patient in the trabeculectomy group (loss of follow-up) was considered successfully treated.
Fisher exact test.
In the PP analysis, 1 patient in the SPI + GSL + GT group was excluded due to reoperation for glaucoma. Similarly, 1 patient in the trabeculectomy group was excluded due to loss of follow-up.
One patient in the SPI + GSL + GT group who underwent reoperation for glaucoma was considered as a treatment failure and included in the PP analysis.
The 95% confidence interval upper limit for the 12-month IOP difference between the groups was 2.2 mm Hg, adjusted for age, sex, hypertension, and CCT, which was within the 4-mm Hg noninferiority margin (Table 2). When a post hoc sensitivity analysis was undertaken using 2.0 mm Hg as the noninferiority margin, the upper limit of the 95% confidence interval (2.2 mm Hg) exceeded this 2.0-mm Hg margin (eFigure 1 in Supplement 2).
Postoperative Glaucoma Medications
The median (IQR) number of medications at baseline and 12 months decreased from 2 (0-3) to 0 (0-1) in the SPI + GSL + GT group and from 2 (2-3) to 0 (0-0) in the trabeculectomy group, with a change difference of −0.81 medications (95% CI, −1.36 to −0.26). At 12 months, the number of medications was not different between the 2 groups (difference, 0; 95% CI, 0-0; P = .09), but the cumulative number of medications was higher in the SPI + GSL + GT group (difference, 0; 95% CI, 0-0; P = .02; eFigure 2 in Supplement 2).
Surgery Success Rates
At 12 months, qualified success rates were not different between the 2 groups (ITT analysis: difference, −5.0%, 95% CI, −19.6% to 8.5%; P = .48; Table 2), with 38 of 43 participants (88.4%) in the SPI + GSL + GT group and 42 of 45 participants (93.3%) in the trabeculectomy group deemed qualified successes. However, the SPI + GSL + GT group had a lower complete success rate than the trabeculectomy group (ITT analysis: 26 of 43 participants [60.5%] vs 37 of 45 participants [82.2%]; difference, −21.8%, 95% CI, −40.2% to −2.4%; P = .03; Table 2).
In the SPI + GSL + GT group, 5 participants (11.6%) experienced treatment failure, with 4 not achieving target IOP and 1 requiring reoperation for glaucoma. In the trabeculectomy group, 3 participants (6.7%) failed to reach the target IOP. Details on treatment failures are in eTable 2 in Supplement 2.
Post Hoc Analyses
Postoperative Complications and Interventions
In the SPI + GSL + GT group, 8 participants (18.6%) experienced 11 postoperative complications, while in the trabeculectomy group, 9 participants (20.0%) had 11 complications. Hyphema and IOP spikes (IOP ≥30 mm Hg) were more common in the SPI + GSL + GT group, with all elevated IOP cases resolved after switching from steroids to nonsteroidal anti-inflammatory eye drops. Most hyphema cases resolved within a week. One patient in the SPI + GSL + GT group developed malignant glaucoma at 3 months requiring reoperation but subsequently recovered. No differences were noted in the total number of complications observed between the groups, as shown in Table 3.
Table 3. Postoperative Complications and Interventions of Participants Over 12 Months of Follow-Up.
| Characteristics | No. (%) | |
|---|---|---|
| SPI + GSL + GT (n = 43) | Trabeculectomy (n = 45) | |
| Complications | ||
| IOP spike (IOP ≥30 mm Hg) | 3 (7.0) | 1 (2.2) |
| Hypotony (IOP <5 mm Hg at any time) | 0 | 2 (4.4) |
| Hyphema | 4 (9.3) | 0 |
| Corneal edema | 0 | 0 |
| Tyndall effect | 1 (2.3) | 0 |
| Shallow anterior chamber | 2 (4.7) | 4 (8.9) |
| Bleb-related complications | 0 | 4 (8.9) |
| Malignant glaucoma | 1 (2.3) | 0 |
| Total No. of postoperative complications | 11 (25.6) | 11 (24.4) |
| Total No. of participants with postoperative complicationsa,b | 8 (18.6) | 9 (20.0) |
| Interventions | ||
| Postoperative mannitol application | 1 (2.3) | 1 (2.2) |
| Paracentesis of anterior chamber | 1 (2.3) | 0 |
| Removal of adjustable sutures | 0 | 8 (17.8) |
| Laser suture lysis | 0 | 6 (13.3) |
| Bleb massage | 0 | 13 (28.9) |
| Bleb needling | 0 | 4 (8.9) |
| Reoperation | 1 (2.3) | 0 |
| Total No. of postoperative interventions | 3 (7.0) | 32 (71.1) |
| Total No. of participants with postoperative interventionsc,d | 3 (7.0) | 25 (55.6) |
Abbreviations: GSL, goniosynechialysis; GT, goniotomy; IOP, intraocular pressure; SPI, surgical peripheral iridectomy.
Some participants had >1 complication.
P = .71 for the difference in rates of postoperative complications between the 2 groups (χ2 test).
Some participants had >1 intervention.
P < .001 for the difference in rates of postoperative interventions between the 2 groups (Fisher exact test).
In terms of interventions, the SPI + GSL + GT group had 3 participants (7.0%) requiring 3 interventions, including an intravenous mannitol injection and anterior chamber paracentesis, both for IOP spikes, and a glaucoma reoperation. In contrast, 25 participants (55.6%) in the trabeculectomy group underwent 32 interventions, predominantly bleb massage, suture lysis, and releasable sutures. The trabeculectomy group required a greater number of postoperative interventions (difference, 48.6%; 95% CI, 32.2%-65.0%; P < .001; Table 3).
Additional Safety and Other Analyses
Both groups experienced a slight decline in BCVA (+0.1 logMAR, approximately 1 Snellen line) without notable differences between them (difference, 0.1 logMAR; 95% CI, −0.1 to 0.2; P = .61). Each group had 1 patient who developed cataract leading to surgery after 12 months. No differences were observed in VF changes, ECD, or EQ-5D-5L scores (eTable 3 in Supplement 2). The SPI + GSL + GT group had a greater reduction in mean (SD) PAS by clock hours compared to the trabeculectomy group (−4.6 [2.7] vs −0.5 [2.5]; difference, −4.1; 95% CI, −5.2 to −2.9; P < .001; eTable 3 in Supplement 2).
The SPI + GSL + GT mean (SD) surgery time was shorter (24.8 [9.1] minutes) than in the trabeculectomy group (35.0 [10.4] minutes; difference, −10.2 minutes; 95% CI, −14.4 to −6.1; P < .001). The mean (SD) surgical costs were not different between the groups ($392.3 [$97.4] vs $351.9 [$99.2]; difference, $40.5; 95% CI, −$1.2 to $82.2; P = .19).
Discussion
This study demonstrated that SPI + GSL + GT was noninferior to trabeculectomy (within a 4-mm Hg margin) in maintaining IOP for advanced PACG without cataract at 12 months postoperatively. Both groups had similar qualified success rates, although the SPI + GSL + GT group had a lower rate of complete success. The SPI + GSL + GT group had fewer postoperative interventions, including bleb massage, suture lysis, and releasable sutures, but no difference in antiglaucoma medications use.
These results align with prior studies finding that trabeculectomy maintained an average IOP of approximately 14 mm Hg after 12 months postsurgery.2,6,7,28 Furthermore, this study found that maintaining IOP with SPI + GSL + GT was noninferior to trabeculectomy. The overall success rates and the number of medications were comparable between the 2 groups at 12 months. These findings support our previous study on advanced PACG with cataract, where GT emerged as a promising alternative to trabeculectomy combined with cataract surgery.16,17 Overall, our research preliminarily confirms the efficacy of GT and GSL for PACG by improving aqueous humor outflow through addressing compromised TM. Moreover, these procedures require shorter surgery times compared to trabeculectomy.
In the trabeculectomy group, 3 participants experienced treatment failure due to bleb scarring over the 12 months, aligning with prior glaucoma filtering surgery studies.6,7,27,29 Conversely, in the SPI + GSL + GT group, 5 participants encountered surgical failure, with 1 participant requiring additional glaucoma surgery for malignant glaucoma. Further investigations using gonioscopy showed that the remaining 4 participants with uncontrolled IOP displayed nearly complete circumferential PAS. Of these, 2 exhibited a nonpupillary block mechanism of angle closure, and 2 had a mixed mechanism by ultrasound biomicroscope examination.30 These results lend additional support to existing research indicating that PAS continues to develop in nonpupillary block mechanisms, even following laser iridotomy.31,32,33,34 However, including all participants who completed the 12-month follow-up in our analysis, we observed a mean reduction of 4.6 clock hours of PAS postoperatively. This implies that PAS still improved after SPI + GSL + GT in most participants.
No sight-threatening complications occurred in either group. Most complications were transient and self-limiting, with incidence rates comparable to or lower than previously reported.6,7,19,20,28,29 In the SPI + GSL + GT group, the most prevalent complications were hyphema and IOP spikes. Hyphema, associated with the incised TM, typically resolved within 1 week in almost all participants. IOP spikes were likely due to the postoperative use of topical steroids.35,36,37 The lower occurrence in our study (7.0%) compared to other ab interno trabeculotomy procedures (>30%) may be attributed to the timely discontinuation of steroid eye drops within 7 days.38,39 Only 1 case of malignant glaucoma occurred 3 months postsurgery, confirming its safety. In the trabeculectomy group, the most common complications included shallow anterior chambers and bleb-related issues, consistent with prior studies.6,7,28,29 Notably, despite maintaining visual acuity postsurgery, 1 patient from each group developed cataract that led to surgery at 12 months.
Consistent with previous studies,6,7,28,29 participants who underwent trabeculectomy required various routine, minor issues (specifically postoperative interventions), such as bleb massage, suture lysis, and releasable sutures. These procedures can be time-consuming for both the surgeon and the patient. In contrast, the SPI + GSL + GT regimen eliminated these needs, significantly reducing them compared to the trabeculectomy group. This resulted in fewer postoperative visits and minimized the negative impact on participants’ quality of life.
Limitations
This study had several limitations. The study included only Chinese participants, which may not represent other ethnic groups; additionally, the small sample size limited generalizability. Lack of surgeon masking may have introduced bias, especially in subjective assessments. This study set a 4-mm Hg noninferiority margin, consistent with a 2019 PACG randomized clinical trial,23 but deviated from the 2- or 2.5-mm Hg criteria for traditional primary open-angle glaucoma studies.27,40,41,42 To further assess efficacy, a post hoc sensitivity analysis was conducted using a 2.0-mm Hg noninferiority margin. The 95% confidence interval upper limit (2.2 mm Hg) exceeded this 2.0-mm Hg margin. Safety differences involved procedures like bleb massage, suture lysis, or releasable sutures, with no differences in antiglaucoma medication numbers. Missing data on VF and ECD at 12 months due to inadequate equipment could have impacted results. Also, only a relatively small number of participants (fewer than 50 in each group) were evaluated, and the 12-month follow-up period was relatively short.
Conclusions
In conclusion, in this randomized clinical trial, the SPI + GSL + GT procedure demonstrated noninferiority to trabeculectomy with a 4-mm Hg margin in maintaining IOP levels at 12 months. This was achieved with fewer interventions, such as bleb massage, suture lysis, and releasable sutures, while showing no difference in the average number of postoperative medications prescribed. These results suggest the potential of SPI + GSL + GT as a viable alternative to trabeculectomy for the patient population enrolled in this trial, particularly if this efficacy is replicated in larger sample sizes with smaller noninferiority margins.
Trial Protocol
eTable 1. The Number of Enrollments and Intraocular Pressure at 12 Months in Each Center
eTable 2. Reasons for Treatment Failure at Month 12 in the Study
eTable 3. Change of Visual Acuity, Visual Field, Gonioscopy, Corneal Endothelial Cell Density and Quality of Life at 12 Months
eFigure 1. A Post Hoc Sensitivity Analysis Was Undertaken Using 2.0 mm Hg as Non-Inferiority Margin
eFigure 2. Cumulative Number of Postoperative Medications
Nonauthor Collaborators
Data Sharing Statement
References
- 1.Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review. JAMA. 2014;311(18):1901-1911. doi: 10.1001/jama.2014.3192 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Gedde SJ, Chen PP, Muir KW, et al. ; American Academy of Ophthalmology Preferred Practice Pattern Glaucoma Panel . Primary angle-closure disease Preferred Practice Pattern®. Ophthalmology. 2021;128(1):30-P70. doi: 10.1016/j.ophtha.2020.10.021 [DOI] [PubMed] [Google Scholar]
- 3.Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology. 2014;121(11):2081-2090. doi: 10.1016/j.ophtha.2014.05.013 [DOI] [PubMed] [Google Scholar]
- 4.Friedman DS, Foster PJ, Aung T, He M. Angle closure and angle-closure glaucoma: what we are doing now and what we will be doing in the future. Clin Exp Ophthalmol. 2012;40(4):381-387. doi: 10.1111/j.1442-9071.2012.02774.x [DOI] [PubMed] [Google Scholar]
- 5.Lai J, Choy BN, Shum JW. Management of primary angle-closure glaucoma. Asia Pac J Ophthalmol (Phila). 2016;5(1):59-62. doi: 10.1097/APO.0000000000000180 [DOI] [PubMed] [Google Scholar]
- 6.Gedde SJ, Feuer WJ, Lim KS, et al. ; Primary Tube Versus Trabeculectomy Study Group . Treatment outcomes in the primary tube versus trabeculectomy study after 3 years of follow-up. Ophthalmology. 2020;127(3):333-345. doi: 10.1016/j.ophtha.2019.10.002 [DOI] [PubMed] [Google Scholar]
- 7.Gedde SJ, Feuer WJ, Lim KS, et al. ; Primary Tube Versus Trabeculectomy Study Group . Treatment outcomes in the primary tube versus trabeculectomy study after 5 years of follow-up. Ophthalmology. 2022;129(12):1344-1356. doi: 10.1016/j.ophtha.2022.07.003 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Jampel HD, Solus JF, Tracey PA, et al. Outcomes and bleb-related complications of trabeculectomy. Ophthalmology. 2012;119(4):712-722. doi: 10.1016/j.ophtha.2011.09.049 [DOI] [PubMed] [Google Scholar]
- 9.Razeghinejad MR, Havens SJ, Katz LJ. Trabeculectomy bleb-associated infections. Surv Ophthalmol. 2017;62(5):591-610. doi: 10.1016/j.survophthal.2017.01.009 [DOI] [PubMed] [Google Scholar]
- 10.Liang YB, Wang NL, Rong SS, Thomas R. Initial treatment for primary angle-closure glaucoma in China. J Glaucoma. 2015;24(6):469-473. doi: 10.1097/IJG.0000000000000075 [DOI] [PubMed] [Google Scholar]
- 11.Dorairaj S, Tam MD, Balasubramani GK. Two-year clinical outcomes of combined phacoemulsification, goniosynechialysis, and excisional goniotomy for angle-closure glaucoma. Asia Pac J Ophthalmol (Phila). 2020;10(2):183-187. doi: 10.1097/APO.0000000000000321 [DOI] [PubMed] [Google Scholar]
- 12.Tanito M, Sugihara K, Tsutsui A, Hara K, Manabe K, Matsuoka Y. Midterm results of microhook ab interno trabeculotomy in initial 560 eyes with glaucoma. J Clin Med. 2021;10(4):814. doi: 10.3390/jcm10040814 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Gupta S, Sethi A, Yadav S, Azmira K, Singh A, Gupta V. Safety and efficacy of incisional goniotomy as an adjunct with phacoemulsification in primary angle-closure glaucoma. J Cataract Refract Surg. 2021;47(4):504-511. doi: 10.1097/j.jcrs.0000000000000481 [DOI] [PubMed] [Google Scholar]
- 14.Shokoohi-Rad S, Karimi F, Zarei-Ghanavati S, Tireh H. Phacoemulsification, visco-goniosynechialysis, and goniotomy in patients with primary angle-closure glaucoma: a comparative study. Eur J Ophthalmol. 2021;31(1):88-95. doi: 10.1177/1120672119879331 [DOI] [PubMed] [Google Scholar]
- 15.Song Y, Xie L, Zhu X, et al. ; PVP study group . Two-year outcome of phacogoniotomy for advanced primary angle-closure glaucoma with cataracts: a multicentre study. Br J Ophthalmol. Published online March 6, 2025. doi: 10.1136/bjo-2024-325375 [DOI] [PubMed] [Google Scholar]
- 16.Song Y, Zhang Y, Li F, et al. ; PVP Study Group . One-year results of a multicenter study: intraocular pressure-lowering effect of combined phacoemulsification, goniosynechialysis, and goniotomy for cases of advanced primary angle-closure glaucoma with cataract. Asia Pac J Ophthalmol (Phila). 2022;11(6):529-535. doi: 10.1097/APO.0000000000000579 [DOI] [PubMed] [Google Scholar]
- 17.Song Y, Lin F, Lv A, et al. ; PVP Study group . Phacogoniotomy versus phacotrabeculectomy for advanced primary angle-closure glaucoma with cataract: a randomized non-inferiority trial. Asia Pac J Ophthalmol (Phila). 2024;13(1):100033. doi: 10.1016/j.apjo.2023.100033 [DOI] [PubMed] [Google Scholar]
- 18.European Glaucoma Society . European Glaucoma Society Terminology and Guidelines for Glaucoma, 4th Edition - Chapter 2: Classification and terminology Supported by the EGS Foundation. Br J Ophthalmol. 2017;101(5):73-127. doi: 10.1136/bjophthalmol-2016-EGSguideline.002 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Lin F, Lu P, Song Y, et al. Surgical outcome and safety of peripheral iridectomy plus goniosynechialysis and goniotomy in the treatment of advanced primary angle-closure glaucoma. Chinese Journal of Experimental Ophthalmology. 2023;41(2):134-139. doi: 10.3760/cma.j.cn115989-20220819-00383 [DOI] [Google Scholar]
- 20.Gao X, Lin F, Lu P, et al. ; TVG study group . Efficacy and safety of surgical peripheral iridectomy, goniosynechialysis, and goniotomy for advanced primary angle closure glaucoma without cataract: 1-year results of a multicenter study. J Glaucoma. 2024;33(9):632-639. doi: 10.1097/IJG.0000000000002443 [DOI] [PubMed] [Google Scholar]
- 21.Gao X, Lv A, Lin F, et al. ; TVG study group . Efficacy and safety of trabeculectomy versus peripheral iridectomy plus goniotomy in advanced primary angle-closure glaucoma: study protocol for a multicentre, non-inferiority, randomised controlled trial (the TVG study). BMJ Open. 2022;12(7):e062441. doi: 10.1136/bmjopen-2022-062441 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Lee EJ. Monitoring progression in advanced glaucoma. Ophthalmology. 2020;127(8):1053. doi: 10.1016/j.ophtha.2020.03.002 [DOI] [PubMed] [Google Scholar]
- 23.Husain R, Do T, Lai J, et al. Efficacy of phacoemulsification alone vs phacoemulsification with goniosynechialysis in patients with primary angle-closure disease: a randomized clinical trial. JAMA Ophthalmol. 2019;137(10):1107-1113. doi: 10.1001/jamaophthalmol.2019.2493 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Shi Y, Wang H, Oatts JT, et al. A prospective study of intraocular pressure spike and failure after gonioscopy-assisted transluminal trabeculotomy in juvenile open-angle glaucoma: a prospective study of GATT in JOAG. Am J Ophthalmol. 2022;236:79-88. doi: 10.1016/j.ajo.2021.10.009 [DOI] [PubMed] [Google Scholar]
- 25.Solomon KD, Cheetham JK, DeGryse R, Brint SF, Rosenthal A. Topical ketorolac tromethamine 0.5% ophthalmic solution in ocular inflammation after cataract surgery. Ophthalmology. 2001;108(2):331-337. doi: 10.1016/S0161-6420(00)00543-1 [DOI] [PubMed] [Google Scholar]
- 26.Gazzard G, Konstantakopoulou E, Garway-Heath D, et al. ; LiGHT Trial Study Group . Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial. Lancet. 2019;393(10180):1505-1516. doi: 10.1016/S0140-6736(18)32213-X [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Baker ND, Barnebey HS, Moster MR, et al. ; INN005 Study Group . Ab-externo microshunt versus trabeculectomy in primary open-angle glaucoma: one-year results from a 2-year randomized, multicenter study. Ophthalmology. 2021;128(12):1710-1721. doi: 10.1016/j.ophtha.2021.05.023 [DOI] [PubMed] [Google Scholar]
- 28.Tham CC, Kwong YY, Baig N, Leung DY, Li FC, Lam DS. Phacoemulsification versus trabeculectomy in medically uncontrolled chronic angle-closure glaucoma without cataract. Ophthalmology. 2013;120(1):62-67. doi: 10.1016/j.ophtha.2012.07.021 [DOI] [PubMed] [Google Scholar]
- 29.Gedde SJ, Schiffman JC, Feuer WJ, Herndon LW, Brandt JD, Budenz DL; Tube versus Trabeculectomy Study Group . Treatment outcomes in the Tube Versus Trabeculectomy (TVT) study after five years of follow-up. Am J Ophthalmol. 2012;153(5):789-803.e2. doi: 10.1016/j.ajo.2011.10.026 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Chen S, Lv J, Fan S, et al. ; Multi-mechanism Angle Closure Study (MACs) group . Laser peripheral iridotomy versus laser peripheral iridotomy plus laser peripheral iridoplasty in the treatment of multi-mechanism angle closure: study protocol for a randomized controlled trial. Trials. 2017;18(1):130. doi: 10.1186/s13063-017-1860-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.He M, Friedman DS, Ge J, et al. Laser peripheral iridotomy in primary angle-closure suspects: biometric and gonioscopic outcomes: the Liwan Eye Study. Ophthalmology. 2007;114(3):494-500. doi: 10.1016/j.ophtha.2006.06.053 [DOI] [PubMed] [Google Scholar]
- 32.Xu BY, Friedman DS, Foster PJ, et al. Ocular biometric risk factors for progression of primary angle closure disease: the Zhongshan Angle Closure Prevention trial. Ophthalmology. 2022;129(3):267-275. doi: 10.1016/j.ophtha.2021.10.003 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.He M, Jiang Y, Huang S, et al. Laser peripheral iridotomy for the prevention of angle closure: a single-centre, randomised controlled trial. Lancet. 2019;393(10181):1609-1618. doi: 10.1016/S0140-6736(18)32607-2 [DOI] [PubMed] [Google Scholar]
- 34.Choi JS, Kim YY. Progression of peripheral anterior synechiae after laser iridotomy. Am J Ophthalmol. 2005;140(6):1125-1127. doi: 10.1016/j.ajo.2005.06.018 [DOI] [PubMed] [Google Scholar]
- 35.Hernandez MR, Wenk EJ, Weinstein BI, et al. Glucocorticoid target cells in human outflow pathway: autopsy and surgical specimens. Invest Ophthalmol Vis Sci. 1983;24(12):1612-1616. [PubMed] [Google Scholar]
- 36.Cassidy PS, Kelly RA, Reina-Torres E, et al. siRNA targeting Schlemm’s canal endothelial tight junctions enhances outflow facility and reduces IOP in a steroid-induced OHT rodent model. Mol Ther Methods Clin Dev. 2020;20:86-94. doi: 10.1016/j.omtm.2020.10.022 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Clark AF, Wordinger RJ. The role of steroids in outflow resistance. Exp Eye Res. 2009;88(4):752-759. doi: 10.1016/j.exer.2008.10.004 [DOI] [PubMed] [Google Scholar]
- 38.Lai J, Qiao Y, Tan C, Chen J. Outcomes of gonioscopy-assisted transluminal trabeculotomy in primary congenital glaucoma treatment: a retrospective study. BMC Ophthalmol. 2024;24(1):88. doi: 10.1186/s12886-024-03351-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Sato T, Kawaji T, Hirata A, Mizoguchi T. 360-Degree suture trabeculotomy ab interno to treat open-angle glaucoma: 2-year outcomes. Clin Ophthalmol. 2018;12:915-923. doi: 10.2147/OPTH.S161238 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40.Gedde SJ, Schiffman JC, Feuer WJ, Parrish RK II, Heuer DK, Brandt JD; Tube Versus Trabeculectomy Study Group . The tube versus trabeculectomy study: design and baseline characteristics of study patients. Am J Ophthalmol. 2005;140(2):275-287. doi: 10.1016/j.ajo.2005.03.031 [DOI] [PubMed] [Google Scholar]
- 41.Scheres LMJ, van den Biggelaar FJHM, Winkens B, et al. Effectiveness and cost-effectiveness of MicroShunt implantation versus standard trabeculectomy for open-angle glaucoma (a SIGHT study): study protocol of a multicentre randomised controlled trial. BMC Ophthalmol. 2023;23(1):43. doi: 10.1186/s12886-022-02734-y [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42.Islamaj E, Wubbels RJ, de Waard PWT. Primary Baerveldt versus trabeculectomy study after one-year follow-up. Acta Ophthalmol. 2018;96(6):e740-e746. doi: 10.1111/aos.13658 [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Trial Protocol
eTable 1. The Number of Enrollments and Intraocular Pressure at 12 Months in Each Center
eTable 2. Reasons for Treatment Failure at Month 12 in the Study
eTable 3. Change of Visual Acuity, Visual Field, Gonioscopy, Corneal Endothelial Cell Density and Quality of Life at 12 Months
eFigure 1. A Post Hoc Sensitivity Analysis Was Undertaken Using 2.0 mm Hg as Non-Inferiority Margin
eFigure 2. Cumulative Number of Postoperative Medications
Nonauthor Collaborators
Data Sharing Statement
