Kahook Dual Blade Goniotomy in Chronic Primary Angle-Closure Glaucoma

Study Background and Rationale Chronic primary angle-closure glaucoma (PACG) is a common ophthalmic disorder characterized by progressive angle closure, impaired aqueous humor outflow, and elevated IOP, which can cause irreversible optic nerve damage and vision loss. Current treatments include medication, laser therapy, and traditional surgery, but traditional combined surgeries for PACG with cataract have limitations such as high complication rates, recurrence, and filtering bleb scarring. PEI-GSL alone often fails to control IOP in long-course patients, leading to a high rate of reoperation.

KDB ab interno goniotomy is a minimally invasive glaucoma surgery that incises and removes ≥120° of trabecular meshwork under gonioscopy to re-establish the communication between Schlemm's canal and the anterior chamber, increasing aqueous outflow with minimal adjacent tissue damage, few complications, and no conjunctival disruption (preserving future surgical options). Previous small-sample studies have shown that PEI-GSL-KDB achieves a 47.2% IOP reduction and 91.7% reduction in hypotensive medications at 12 months postoperatively in PACG patients, with improved visual acuity. However, large-sample randomized controlled trials (RCTs) on this regimen are lacking, necessitating this study to provide high-quality evidence for clinical practice.

Study Objectives The primary objective is to compare the effects of PEI-GSL and PEI-GSL-KDB on IOP in patients with chronic PACG. Secondary objectives include evaluating the safety (intra- and post-operative complications) and changes in PAS of the two surgical approaches.

Study Design and Methods Study Design A prospective randomized controlled trial with a 1:1 allocation ratio of patients to the experimental group (PEI-GSL-KDB) and the control group (PEI-GSL). The random sequence is generated by an independent ophthalmologist using Excel, stored in a password-protected file, with allocation concealment until data analysis is completed.

Study Population Inclusion Criteria: Consecutive PACG patients complicated by age-related cataract, without signs of previous acute angle closure; PAS >90° with persistent IOP elevation (>21 mmHg) via fundoscopy; presence of glaucomatous optic neuropathy or visual field defect; poor disease control eligible for surgery.

Exclusion Criteria: A history of intraocular surgery/laser therapy; secondary angle closure due to ocular trauma, iris neovascularization, tumors, uveitis, lens swelling/dislocation; unclear diagnosis based on history, symptoms and signs.

Sample Size: Calculated based on an expected 4.9 mmHg IOP difference between groups, 88% power, and α=0.05, requiring 31 patients per group. With a 10% loss to follow-up rate, 34 eyes per group (68 total) are enrolled.

Interventions PEI-GSL-KDB Group (Experimental): Cataract phacoemulsification + intraocular lens implantation + goniosynechialysis + KDB ab interno goniotomy (incising trabecular meshwork to enhance aqueous outflow).

PEI-GSL Group (Control): Cataract phacoemulsification + intraocular lens implantation + goniosynechialysis (the standard surgery for PACG with proven IOP control efficacy and low complications).

Outcome Measures Primary Outcome: 12-month IOP control success rate (IOP ≤21 mmHg and ≥20% reduction from baseline, with/without topical hypotensive medications).

Secondary Outcomes: ① Intra-operative complications (posterior capsule rupture, iris prolapse, zonular dialysis); ② Post-operative complications (hyphema, IOP spike); ③ Changes in PAS (clock hours) from baseline to 12 months via gonioscopy.

Follow-up Plan Patients are followed up by glaucoma specialists at 1 day, 1 week, 1 month, 3 months, 6 months, and 12 months postoperatively. Follow-up examinations include best-corrected visual acuity, applanation tonometry, slit-lamp examination, gonioscopy, ultrasound biomicroscopy, Heidelberg optical coherence tomography, and visual field testing (if glaucomatous damage is present).

Study Timeline Jan-Dec 2024: Recruit patients, randomize allocation, perform surgeries, and collect baseline clinical data (IOP, PAS, optic neuropathy, visual field defect).

Jan-Jun 2025: Conduct 1-year postoperative follow-up, record outcome measures and complications, and calculate IOP control success rates.

Jul-Dec 2025: Complete data analysis, and write a research paper to explore the efficacy, safety, indications and disadvantages of the two surgical regimens.

Preliminary Research Basis The research team previously studied 22 eyes of 20 PACG patients who underwent phacoemulsification + intraocular lens implantation + goniosynechialysis + trabecular ablation (2017.09-2020.09). The results showed a significant IOP reduction from 22.07±6.62 mmHg (baseline) to 15.06±3.39 mmHg (12 months, p=0.001), a sharp decrease in hypotensive medication use from 2.68±1.17 to 0.78±0.73 times (p<0.01), and an 88.9% 12-month surgical success rate. No vision-threatening complications occurred, confirming the safety and efficacy of combined glaucoma-cataract surgeries, especially for PACG patients with long-term and extensive PAS.

Study Site and Data Management Study Site: Baita Temple Campus of Peking University People's Hospital, with data processed and protected in accordance with international standards and ethical norms.

Data Management: Electronic Case Report Forms (eCRF) are used for data collection. Data managers perform entry, verification (logical, range, normative checks) and cleaning; data quality controllers conduct audit for validity, credibility and completeness. After follow-up and verification, the database is locked, backed up, and exported in standard formats (SAS, SPSS, Excel) for encrypted transmission to the research team for analysis.

Statistical Analysis Intention-to-treat (ITT) analysis is adopted. Continuous variables (IOP, age) are compared using t-tests or Wilcoxon rank-sum tests; categorical variables (gender, IOP control success rate) use chi-square tests or Fisher's exact test; repeated measurement data (IOP, PAS changes) are analyzed via mixed-effects models or repeated measures ANOVA. All analyses are performed with SPSS 26.0, with P<0.05 indicating statistical significance.

Safety Evaluation Adverse Events (AE): All adverse medical events during the study are recorded in AE forms and reported to the ethics committee. Corresponding measures (dose adjustment, intervention suspension, symptomatic treatment) are taken for AE related to the intervention.

Serious Adverse Events (SAE): Events resulting in death, life-threatening conditions, hospitalization/prolonged hospitalization, persistent disability, congenital malformations, or requiring immediate intervention are reported to the ethics committee and study leader within 24 hours via SAE forms. The intervention is immediately terminated for SAE related to the study, with necessary treatment provided.

Subject Protection The study adheres to the Declaration of Helsinki. All participants sign an informed consent form before surgery, with clear explanation of the study purpose, procedures, potential risks/benefits, and the right to withdraw. Personal information and clinical data are strictly confidential and only used for study analysis and reporting.

Study Management Protocol Modification: Modifications are only made for scientific/ethical reasons, approved by the research team, notified to all participants, updated on the study registration platform, and stated in the final publication.

Quality Control: Training for researchers, calibration of equipment, and verification of materials in the preparation stage; strict subject screening, standardized intervention, and regular supervision during implementation; accurate data collection, encrypted backup, and rigorous audit in data management.

Early Termination: The study may be terminated early if severe SAEs threaten subject safety, the intervention effect is significantly higher/lower than expected, severe bias/error affects reliability, or ethical/legal violations occur. Termination reasons are notified to participants and registered, with collected data analyzed and reported if possible.

Research Team The study is led by Chief Physician Huijuan Wu (Peking University People's Hospital, Ophthalmology), with the team including Attending Physician Zhiqiao Liang and resident physicians Kun Lv, Ye Lu, Kuankuan Wu, Yao Ma. The team is responsible for literature retrieval, study design, clinical data collection/entry, follow-up, and paper writing.