Ab Externo Canaloplasty Alone or Combined with Phacoemulsification for Advanced Primary Open-Angle Glaucoma

Summary

This protocol evaluates and compares the clinical efficacy, safety, and patient-reported outcomes of ab externo canaloplasty performed alone or in combination with phacoemulsification in eyes with advanced primary open-angle glaucoma, providing a standardized approach for assessing long-term intraocular pressure control, structural preservation, and quality-of-life improvement.

Abstract

Advanced primary open-angle glaucoma (POAG) requires surgical strategies that achieve effective reduction of intraocular pressure (IOP) while preserving optic nerve structure and function. This study aims to compare the long-term clinical performance of ab externo canaloplasty (AC) alone versus AC combined with phacoemulsification (AC + phaco) in patients with advanced POAG. In this retrospective comparative study, 140 patients with advanced POAG were assigned to AC (n = 70) or AC + phaco (n = 70). Over 24 months of follow-up, both procedures significantly reduced IOP and medication use. However, AC + phaco achieved greater mean IOP reduction (45.5% vs. 36.1%; p < 0.001), higher retinal nerve fiber layer thickness (62.55 ± 6.03 µm vs. 60.82 ± 6.51 µm; p = 0.047), larger neuroretinal rim area (0.91 ± 0.12 mm² vs. 0.85 ± 0.12 mm²; p = 0.009), and improved visual field stability. Quality-of-life measures favored AC + phaco, with improved patient-reported visual function and fewer vision-related limitations. These findings demonstrate that both AC and AC + phaco are safe and effective surgical options for advanced POAG. AC + phaco may be preferentially selected in patients with coexisting cataract or in cases requiring enhanced long-term IOP control and structural preservation, without increasing surgical risk.

Introduction

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy and the second leading cause of irreversible blindness worldwide¹. It is characterized by the degeneration of retinal ganglion cells and optic nerve fibers, resulting in progressive visual field loss and eventual visual disability. Due to its insidious onset and largely asymptomatic early course, POAG is often diagnosed only after substantial structural and functional damage has occurred. With increasing global life expectancy, urbanization, and population aging, the burden of POAG continues to rise, particularly in low- and middle-income regions where access to early screening and sustained care remains limited². In addition to visual impairment, POAG imposes significant socioeconomic and quality-of-life burdens, highlighting the need for surgical strategies that achieve durable intraocular pressure (IOP) control while preserving optic nerve structure and functional vision.

Conventional glaucoma surgeries, including trabeculectomy and glaucoma drainage device implantation, have long been considered the standard surgical options for eyes with uncontrolled IOP. Although effective in lowering pressure, these procedures are associated with well-recognized complications such as hypotony, bleb leakage, infection, and long-term bleb-related morbidity³. The reliance on subconjunctival filtration also necessitates intensive postoperative management and may compromise ocular surface integrity over time. To overcome these limitations, Schlemm's canal-based procedures and minimally invasive glaucoma surgeries have been developed to restore physiologic aqueous humor outflow while minimizing tissue disruption⁴. These approaches preserve conjunctival integrity, reduce complication rates, and allow faster visual recovery, making them increasingly relevant across the glaucoma severity spectrum^5,6.

Ab externo canaloplasty (AC) is a bleb-independent Schlemm's canal-based procedure designed to enhance trabecular outflow by circumferential dilation of Schlemm's canal under a watertight scleral flap^7,8,9. By avoiding subconjunctival filtration, this technique reduces bleb-related complications, simplifies postoperative care, and preserves future surgical options^10,11,12,13. These features have supported its use primarily in early and moderate POAG; however, its application in advanced disease remains an area of active investigation¹⁴. Importantly, AC maintains the native aqueous outflow pathway, offering a physiologic alternative to filtering surgery in appropriately selected patients.

Combining AC with phacoemulsification (AC + phaco) offers potential additional benefits, particularly in older patients with coexisting cataract. Cataract extraction alone is known to lower IOP modestly by widening the anterior chamber angle and improving aqueous outflow dynamics^15,16,17. When combined with AC, phacoemulsification may enhance outflow facility while simultaneously restoring visual acuity, thereby improving both functional vision and quality of life^{18,19,20,21,22}. This combined approach may be especially advantageous in patients with visually significant lens opacity, advanced glaucoma, and a need for sustained IOP reduction with minimal postoperative risk.

Despite these advantages, concerns persist regarding the safety and efficacy of combining cataract surgery with Schlemm's canal-based procedures in eyes with advanced optic nerve damage, given the potential inflammatory and hemodynamic stresses associated with phacoemulsification^23,24. However, emerging evidence from longitudinal studies, matched cohort analyses, and multicenter registries suggests that AC combined with phacoemulsification may provide superior preservation of retinal nerve fiber layer thickness, neuroretinal rim area, and visual field stability compared with canaloplasty alone^{25,26,27,28,29}. Additional studies have demonstrated improved patient-reported quality-of-life outcomes, reduced dependence on anti-glaucoma medications, and durable IOP control extending beyond two years^30,31. These findings underscore the importance of integrating structural, functional, and patient-centered metrics when evaluating surgical options for advanced POAG^{32,33,34,35,36,37}.

Both procedures may be less suitable in patients with angle-closure glaucoma, extensive peripheral anterior synechiae, or secondary glaucomas such as neovascular or active uveitic glaucoma, where trabecular outflow resistance is not the primary mechanism of pressure elevation. Eyes requiring very low target IOP, particularly in the low teens or single-digit range due to rapidly progressive disease, may be better managed with filtering surgery or drainage devices. Prior conjunctival or scleral surgery, distorted Schlemm's canal anatomy, or ocular comorbidities that limit reliable structural and functional assessment may also reduce the feasibility or interpretability of outcomes with this approach.

The overall goal of the present method is to provide a reproducible surgical approach to evaluate the long-term efficacy, safety, and functional impact of AC performed alone or in combination with phacoemulsification in advanced POAG.

Protocol

All procedures described in this protocol were reviewed and approved by the Institutional Human Research Ethics Committee of the Third People's Hospital of Dalian University of Technology (Approval No. 2025-176-001). The study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. Informed consent was obtained from all participants prior to enrollment.

1. Patient recruitment and screening

NOTE: Patients were recruited consecutively and concurrently from the glaucoma outpatient clinic of the Third People's Hospital of Dalian University of Technology between January 2020 and December 2022.

1. Confirm eligibility using the following inclusion criteria:
   1. Ensure patient age is between 50 and 80 years.
   2. Confirm diagnosis of advanced primary open-angle glaucoma (POAG) defined by a visual field mean deviation (MD) ≤−12 dB, cup-to-disc ratio ≥0.8, and significant retinal nerve fiber layer (RNFL) thinning on optical coherence tomography (OCT).
   3. Verify uncontrolled IOP (≥21 mmHg) despite maximal tolerated anti-glaucoma medical therapy.
   4. Confirm the patient's ability to provide written informed consent and comply with scheduled postoperative follow-up visits.
2. Exclude patients with a history of glaucoma filtering or cyclodestructive surgery, secondary glaucomas, active ocular infection or inflammation, advanced systemic illness, visually significant corneal opacity or retinal pathology, or pseudophakic/aphakic eyes at baseline.
3. Screen all eligible patients during the same enrollment period to minimize temporal bias related to surgical experience or procedural refinement.

2. Group allocation

1. After excluding individuals who do not meet eligibility requirements or decline participation, enroll eligible patients with advanced primary open-angle glaucoma.
2. Allocate them in comparable numbers to either AC alone or AC + phaco based on clinical indication and lens status (Figure 1).

Figure 1: Patient enrollment and group allocation flow diagram. Flow diagram illustrating patient screening, eligibility assessment, exclusions, and final allocation to the AC group or the AC + phaco group. Abbreviations: AC = ab externo canaloplasty; AC + phaco = ab externo canaloplasty combined with phacoemulsification; POAG = primary open-angle glaucoma. Please click here to view a larger version of this figure.

3. Preoperative evaluation

1. Measure Best Corrected Visual Acuity (BCVA) using a Snellen chart under standardized lighting.
2. Record IOP using Goldmann applanation tonometry. Take three consecutive readings and calculate the mean.
3. Perform gonioscopy to assess the anterior chamber angle.
4. Conduct slit-lamp biomicroscopy to examine anterior segment structures.
5. Use spectral-domain OCT to measure RNFL thickness and neuroretinal rim area.
6. Capture fundus photographs of the optic disc for baseline documentation.
7. Perform automated perimetry (24-2 SITA-Standard protocol) to evaluate visual fields.

4. Surgical intervention

1. General surgical conditions
   1. Perform all surgical procedures by the same experienced glaucoma surgeon throughout the study period to minimize inter-operator variability.
   2. Perform all procedures under local anesthesia using standard sterile ophthalmic technique.
   3. Position the patient supine and prepare and drape the operative field in the usual manner.
2. Ab externo canaloplasty alone (AC group)
   1. Create a fornix-based conjunctival peritomy in the superior quadrant.
   2. Dissect Tenon's capsule to expose bare sclera and achieve meticulous hemostasis.
   3. Fashion a superficial scleral flap measuring approximately 4 × 4 mm, followed by a deep scleral flap to expose and unroof Schlemm's canal.
      ​NOTE: Accurate identification and exposure of Schlemm's canal is critical, as incorrect flap depth or canal misidentification is the most frequent source of technical failure.
   4. Identify the two ostia of Schlemm's canal and confirm correct localization.
   5. Introduce a flexible microcatheter into Schlemm's canal and advance it circumferentially through 360°.
      ​NOTE: Confirm complete circumferential passage before proceeding. Recognize incomplete canal cannulation by resistance to catheter advancement or failure to visualize the catheter tip, and reassess canal localization if this occurs.
   6. Inject viscoelastic material incrementally during catheter withdrawal to achieve uniform canal dilation.
      NOTE: Identify inadequate viscodilation by minimal early postoperative IOP reduction.
   7. Place a 10-0 Prolene suture within Schlemm's canal and apply moderate, evenly distributed tension to obtain circumferential canal distension.
      ​NOTE: Avoid under- or over-distension. Recognize over-tensioning by early postoperative IOP spikes or patient discomfort.
   8. Reposition the superficial scleral flap and secure it with interrupted 10-0 nylon sutures.
   9. Close Tenon's capsule and conjunctiva with interrupted 10-0 nylon sutures to prevent wound leakage and postoperative hypotony.
      ​NOTE: Mild hyphema and transient IOP fluctuations in the early postoperative period are common and typically self-limiting, reflecting restoration of physiologic outflow rather than surgical failure.
3. Combined Ab externo canaloplasty with phacoemulsification (AC + phaco group)
   1. Perform the standard clear corneal phacoemulsification using the divide-and-conquer technique.
   2. Remove the crystalline lens and implant a foldable acrylic intraocular lens into the capsular bag. Hydrate corneal incisions and confirm watertight wound closure.
   3. Proceed with AC as described for the AC group.
4. Create a superior conjunctival peritomy, fashion superficial and deep scleral flaps, identify Schlemm's canal, and perform circumferential microcatheterization with incremental viscoelastic injection.
5. Insert and tension a 10-0 Prolene suture to achieve uniform canal distension. Reposition and secure the scleral flap and close the conjunctiva with interrupted 10-0 nylon sutures.

5. Postoperative evaluation and follow-up

1. 5.1.Conduct follow-up assessments at 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months.
2. At each visit, repeat BCVA, IOP measurement, slit-lamp examination, and gonioscopy.
3. Perform OCT imaging and fundus photography annually.
4. Assess visual fields at 6, 12, and 24 months.
5. Document postoperative complications, dividing into early (<30 days) or late (>30 days). Include hyphema, IOP spikes, shallow anterior chamber, infection, and need for reintervention.
6. Record medication burden by counting topical anti-glaucoma agents used at each follow-up.

6. Quality-of-life assessment

1. Administer the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) to assess vision-related quality of life.
   NOTE: The NEI VFQ-25 assesses vision-related functional status across multiple domains, including general vision, near and distance activities, social functioning, mental health, and role limitations.
2. Administer EuroQol-5D (EQ-5D) to evaluate general health-related quality of life.
   NOTE: The EQ-5D evaluates general health-related quality of life across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
3. Administer Glaucoma Quality of Life-15 (GQL-15) to measure glaucoma-specific disability.
   NOTE: The GQL-15 specifically measures glaucoma-related disability, focusing on difficulties with central and peripheral vision, dark adaptation, glare, and outdoor mobility.
4. Conduct all questionnaires in the patient's preferred language with trained personnel.

7. Outcome measures

1. Record primary outcomes:
   1. IOP reduction at each follow-up relative to baseline. 
   2. Stability of RNFL thickness and neuroretinal rim area on OCT.
      NOTE: The change in retinal nerve fiber layer (RNFL) thickness is analyzed as the difference from baseline (ΔRNFL) at each follow-up time point to reflect longitudinal structural preservation.
   3. Quality-of-life scores from NEI VFQ-25, EQ-5D, and GQL-15.
   4. Complete success, defined as IOP ≤18 mmHg without medications
   5. Qualified success, defined as IOP ≤18 mmHg with medications
2. Record secondary outcomes: 
   1. Change in visual field indices. 
   2. Reduction in medication burden. 
   3. Frequency and severity of complications.

8. Statistical analysis

1. Enter all data into SPSS software (version 26.0; IBM Corp., Armonk, NY, USA) for statistical analysis.
2. Assess the normality of continuous variables using the Shapiro-Wilk test. Present normally distributed data as mean ± standard deviation (SD) and non-normally distributed data as median (interquartile range).
3. Perform between-group comparisons using the independent-samples t-test for normally distributed continuous variables and the Mann-Whitney U test for non-normally distributed variables. Use repeated-measures ANOVA to evaluate within-group longitudinal changes across follow-up time points.
4. Analyze categorical variables using the chi-square test or Fisher's exact test, as appropriate.
5. Consider a p value ≤ 0.05 as statistically significant for all analyses.
6. Perform Kaplan-Meier survival analysis to evaluate long-term surgical success according to predefined IOP control thresholds, with group differences assessed using the log-rank test.

Results

A total of 200 patients were assessed for eligibility. After excluding patients who did not meet the inclusion criteria or declined to participate, 140 patients with advanced POAG were enrolled and allocated into two groups: AC (n = 70) and AC + phaco (n = 70) (Figure 1).

Baseline clinical characteristics were comparable between the AC group and the AC + phaco group (Table 1). No statistically significant differences were observed between groups i...

Discussion

The efficacy of Schlemm’s canal–based strategies in slowing the progression of POAG is demonstrated by the consistent IOP reduction pattern observed in both groups. However, statistical analysis showed that the AC + phaco group achieved superior pressure-reducing effects at all postoperative time points. These results are supported by Zhang and Wang³⁸ and Seethe et al.³⁹, who reported significantly greater IOP reduction with combined canaloplasty and phacoemulsi...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Equipment
Automated perimeter (HFA 24-2 SITA-Standard)	Carl Zeiss Meditec	ZEISS-HFA3-860	Visual field indices: MD, PSD at 6, 12, 24 months.
Canaloplasty microcatheter	Nova Eye Medical (iTrack)	NOVA-ITRACK-250	360° Schlemm’s canal catheterization for viscodilation.
Fundus camera / Imaging system	ZEISS (VISUCAM)	ZEISS-VISC-524	Optic disc and posterior pole documentation.
Goldmann applanation tonometer	Haag-Streit AG	HS-GAT-870	Standard IOP measurement; three consecutive readings averaged.
Gonioscopy lens (4-mirror)	Volk Optical	VOLK-G4	Pre-/post-operative angle assessment.
Ophthalmic operating microscope	ZEISS (OPMI Lumera series)	ZEISS-LUMERA-T	Microsurgical visualization.
Phacoemulsification system	Alcon (CENTURION)	ALC-CENT-PHACO	Divide-and-conquer technique; used only in PCP+Phaco group.
Slit-lamp biomicroscope	Topcon	TOP-SLD701	Anterior segment examination and postoperative monitoring.
Spectral-domain OCT (RNFL/GCC)	Heidelberg Engineering (SPECTRALIS)	HE-SDOCT-SPC	Peripapillary RNFL thickness and neuroretinal rim area acquisition.
Consumable
Balanced salt solution (BSS)	Alcon	ALC-BSS-500	Irrigation during anterior segment surgery.
Foldable posterior chamber IOL	Alcon (AcrySof IQ)	ALC-SN60WF	IOL power individualized; acrylic lens implantation.
Microsurgical sutures, Nylon 10-0	Ethicon	ETH-NYL-10-0	Watertight scleral flap closure.
Ophthalmic viscosurgical device (OVD), 1.0% Sodium hyaluronate	Johnson & Johnson Vision (Healon)	JJ-HEALON-10	Maintains anterior chamber; viscodilation support.
Viscodilation cannula (27G)	Nova Eye Medical	NOVA-VD-27G	Controlled viscoelastic delivery into Schlemm’s canal.
Drug
Moxifloxacin 0.5% Ophthalmic solution	Alcon (Vigamox)	ALC-VIG-05	Postoperative topical antibiotic.
Prednisolone acetate 1% Ophthalmic suspension	Allergan (Pred Forte)	AGN-PF-1	Postoperative topical steroid taper.
Timolol 0.5% / Brimonidine 0.2% / Dorzolamide 2% / Latanoprost 0.005%	Various (Generic/Branded)	GLC-RESCUE-SET	IOP-lowering agents as needed per protocol.
Software/Instrument
EQ-5D Instrument (License)	EuroQol Research Foundation	EQ-5D-LIC	General health-related quality of life.
GQL-15 Questionnaire (Permission)	Instrument Owner/Publisher	GQL-15-PERM	Glaucoma-specific disability index.
NEI VFQ-25 Questionnaire (License/Permission)	National Eye Institute	NEI-VFQ25-LIC	Vision-related quality of life assessment.
SPSS Statistics v26	IBM	IBM-SPSS-26	Statistical analysis: t-tests, ANOVA, repeated measures, Kaplan–Meier.