Phacogoniotomy for advanced primary angle-closure glaucoma, from conceptual appeal to randomized evidence

Introduction

Primary angle-closure glaucoma (PACG) remains a formidable clinical challenge and a leading cause of irreversible vision loss worldwide. Although less common than open-angle glaucoma, it contributes disproportionately to blindness, particularly in Asian populations where anatomical predisposition and demographic factors converge (1). As populations age, the absolute number of individuals affected by PACG is projected to increase substantially, underscoring the urgency of refining surgical strategies that are both effective and durable (1).

Cataract commonly accompanies advanced PACG, contributing not only to visual impairment but also to lens-induced angle crowding and pupillary block mechanisms, that further compromise the angle. Surgical management therefore becomes unavoidable as disease progresses (2). For decades, trabeculectomy, often combined with phacoemulsification in the presence of cataract has been regarded as the definitive surgical option for achieving substantial intraocular pressure (IOP) reduction in PACG (3). However, the long-term realities of bleb-dependent surgery, including complications, demanding postoperative care, and variability in sustained outcomes, have encouraged clinicians to reconsider whether alternative approaches that more directly target the mechanisms of angle closure (3-8).

In this context, the emergence of angle-based surgical strategies, particularly phacogoniotomy has begun to challenge the traditional assumptions regarding the irreversibility of trabecular dysfunction in advanced PACG (9,10). By combining phacoemulsification with goniotomy, with or without goniosynechialysis (GSL), this approach seeks to directly address multiple anatomical contributors to outflow resistance rather than relying solely on bleb-dependent filtration surgery. The recently published 2-year randomized non-inferiority trial by Song and colleagues, comparing phacogoniotomy with phacotrabeculectomy represents an important turning point in this evolving paradigm (11). By extending follow-up beyond the previously reported study (12), the study confronts a question that has historically limited wider adoption of angle-based procedures in advanced disease: the durability of outcomes in advanced disease.

Reconsidering surgical dogma in advanced PACG

Traditional surgical decision-making in advanced PACG has long been shaped by the assumption that extensive peripheral anterior synechiae (PAS) signify irreversible trabecular dysfunction, thereby limiting the potential role of angle-based interventions. However, histopathologic evaluation of trabeculectomy specimens in PACG has demonstrated that damage to the trabecular meshwork and juxtacanalicular tissue is often segmental and heterogeneous, extending beyond areas of clinically apparent PAS and involving variable regions across different clock hours, even in advanced stages (13,14). While neither histopathologic nor imaging studies provide direct evidence of restoration of physiological aqueous outflow following relief of appositional or synechial closure, clinical studies incorporating GSL with trabecular incision or excision have consistently demonstrated meaningful IOP reduction. These outcomes suggest that surgical strategies which reopen the angle and bypass diseased trabecular meshwork, may enhance effective aqueous egress through residual and segmentally preserved outflow channels, thereby achieving sustained IOP control without reliance on bleb formation (15-18).

Mechanistic rationale for phacogoniotomy

Phacogoniotomy brings together several complementary mechanisms within a single procedure, each addressing a key component of PACG pathophysiology. Cataract extraction alleviates lens-induced anterior segment crowding, GSL relieves mechanical angle obstruction, and goniotomy directly targets trabecular outflow resistance (2,19-24). Collectively, this approach seeks to re-engage the conventional outflow pathway by maximizing utilization of residual trabecular function, rather than bypassing it altogether. This mechanistic alignment distinguishes phacogoniotomy from bleb-dependent filtering surgery and provides a biologically plausible explanation for its observed efficacy, even in eyes with advanced disease and extensive PAS.

The Song et al. trial: a landmark in evidence maturation

Song and colleagues have advanced the evidence base for angle-based surgery in advanced PACG through a carefully staged investigative program. Initial one-year data demonstrated substantial IOP reduction and medication sparing following phacogoniotomy in advanced PACG (21). This was followed by a multicenter 2-year observational study confirming durability beyond the first postoperative year (22). The randomized non-inferiority trial published in 2024–2025 represents the culmination of this investigative trajectory (11,12).

In this multicenter study, eyes with advanced PACG and visually significant cataract were randomized to phacogoniotomy or phacotrabeculectomy. Conducted across seven tertiary centers in China, the study enrolled 124 patients and applied a rigorous noninferiority framework, with a prespecified margin of 4 mmHg for IOP reduction (11). As noninferiority margins are inherently trial-specific and reflect a balance between statistical considerations and clinical judgment, their interpretation requires clinical context. In advanced PACG, where target IOP are often in the low teens, even modest differences in IOP may be clinically meaningful in terms of disease progression risk, and this should be considered when interpreting the trial findings (25,26). At 24 months, mean IOP reduction was 25.6 mmHg in the phacogoniotomy group and 24.7 mmHg in the phacotrabeculectomy group, meeting the prespecified noninferiority margin.

Importantly, no significant between-group differences were observed beyond the primary outcome. Rates of complete surgical success (78% vs. 84.6%) and qualified success (89.8% vs. 88.5%) did not differ significantly between phacogoniotomy and phacotrabeculectomy, respectively, and both groups achieved profound medication reduction, with a median of zero antiglaucoma medications at two years. Functional and structural secondary outcomes, including visual field indices, best-corrected visual acuity, and corneal endothelial cell density (ECD) were comparable between treatment arms. Corneal ECD declined over follow-up in both groups, with 24.2% reduction in the phacogoniotomy group and 26.2% in the phacotrabeculectomy group. Importantly, the addition of goniotomy with phacoemulsification was not associated with greater ECD loss compared with phacotrabeculectomy. Notably, no additional late complications emerged during the extended follow-up period, and recurrent PAS in the phacogoniotomy group were not associated with surgical failure or inadequate IOP control.

Beyond efficacy and safety, the trial highlights practical considerations that are particularly relevant in real-world settings. Phacogoniotomy was associated with significantly shorter operative duration compared with phacotrabeculectomy, while overall procedural costs were similar under the standardized healthcare framework. Coupled with the absence of bleb-related morbidity and the relative simplicity of postoperative management, these findings underscore the potential system-level advantages of a bleb-independent strategy for advanced PACG.

While the randomized trial by Song et al. provides the highest level of evidence to date, it is important to recognize that these findings build upon a growing body of clinical experience with phacogoniotomy in PACG. A summary of key published studies evaluating phacogoniotomy in PACG is presented in Table 1, highlighting the progressive maturation of evidence leading to the present randomized trial.

Strengths and limitations

The strengths of this trial include its multicenter design, rigorous randomization, standardized surgical protocols, and high follow-up completion rates. The inclusion of advanced PACG, rather than early or moderate disease addresses a population in whom surgical decision-making is most challenging and clinically consequential.

Nevertheless, certain limitations warrant consideration. The study population was ethnically homogeneous, potentially limiting generalizability to non-Asian eyes with different angle configurations or wound-healing responses. Surgeons were not masked to treatment allocation, an inherent challenge in surgical trials, which may influence postoperative management. Additionally, while 2-year outcomes are reassuring, longer follow-up will be essential to determine whether these comparable outcomes persist over 5 years or beyond.

Phacogoniotomy in the broader minimally invasive glaucoma surgery (MIGS) landscape

MIGS has transformed glaucoma management over the past decade, primarily in open-angle disease (4,27). However, early MIGS frameworks largely excluded PACG, reflecting anatomical constraints and limited data. More recent systematic reviews and meta-analyses have begun to address this gap. Paik et al. provided a comprehensive meta-analysis demonstrating that MIGS procedures can achieve significant IOP reduction in PAC and PACG when combined with cataract surgery, albeit with heterogeneity across techniques (9). Chan et al. further emphasized that angle-based MIGS in PACG should be viewed not as inferior substitutes but as mechanistically appropriate interventions when angle anatomy permits (10).

Several angle-based techniques have been explored in PACG, including Trabectome (18,28,29), microhook ab interno trabeculotomy (30), excisional goniotomy with the Kahook Dual Blade (24,31), and gonioscopy-assisted transluminal trabeculotomy (GATT) combined with GSL (32). Collectively, these studies demonstrate that trabecular outflow can be meaningfully enhanced in angle-closure eyes once synechiae are addressed. Within this expanding landscape, phacogoniotomy distinguishes itself by integrating synechial release and trabecular incision into a single, cohesive procedure tailored specifically to PACG pathophysiology.

Comparative studies, including the randomized trial by Song et al. (11,12) and observational data from other center (22), demonstrate IOP control comparable to trabeculectomy while avoiding bleb-specific risks. Risk factor analyses further suggest that failure after phacogoniotomy is more closely related to the extent and chronicity of PAS than to patient age or wound modulation variables (33).

Clinical implications and future directions

The accumulating evidence supports a shift away from a rigid surgical hierarchy toward individualized, mechanism-based decision-making. Phacogoniotomy may be particularly well suited for eyes requiring substantial IOP reduction but not ultra-low target pressures, for patients at high risk of bleb-related complications, and for settings where intensive postoperative follow-up is challenging.

Importantly, these findings do not diminish the role of trabeculectomy. Rather, they refine its indication, reserving bleb-dependent surgery for eyes with extensive, non-recoverable angle pathology or those requiring very low target IOPs.

Future studies with longer follow-up, comparative trials against other angle-based techniques, and integration of structural imaging and patient-reported outcome measures (PROMs) will further define the role of phacogoniotomy. Notably, while the Song et al. 1-year study reported improved quality-of-life outcomes (EQ-5D-5L) with phacogoniotomy, such measures were not included in the 2-year follow-up, underscoring the need for consistent incorporation of PROMs in future trials. Adherence to established guidelines for the design and reporting of glaucoma surgical trials will be essential as the field continues to evolve (34).

Conclusions

The evolution of evidence surrounding phacogoniotomy reflects a broader maturation in glaucoma surgery, from bypassing diseased anatomy toward strategically re-engaging the conventional outflow pathway. The findings from the 2-year randomized trial support the consideration of phacogoniotomy as an alternative to phacotrabeculectomy in selected patients with advanced PACG and cataract, while long-term outcomes and broader validation across diverse populations remain to be established. As surgical philosophy continues to shift toward mechanism-based, patient-centered care, phacogoniotomy emerges not as a compromise, but as a rational and evidence-based choice.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, AME Clinical Trials Review. The article has undergone external peer review.

Peer Review File: Available at https://actr.amegroups.com/article/view/10.21037/actr-26-0016/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://actr.amegroups.com/article/view/10.21037/actr-26-0016/coif). S.G. is an employee of iClinix Advanced Eye Care. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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