Deconstructing Anterior Segment Crowding: Preoperative Anatomical Predictors of Malignant Glaucoma After Primary Angle-Closure Glaucoma Surgery

Summary

Preoperative ultrasound biomicroscopy reveals that a shortened simulated cilio-lenticular distance, increased lens vault, and narrowed trabecular-ciliary process angle are exploratory anatomical clusters significantly associated with malignant glaucoma development following primary angle-closure glaucoma surgery.

Abstract

Understanding anterior segment crowding is essential for identifying preoperative risk factors for malignant glaucoma (MG) following phacoemulsification, intraocular lens implantation, and goniosynechialysis (PEI‒GSL) in primary angle-closure glaucoma (PACG). This retrospective case-control study compared 24 PACG patients who developed postoperative MG (MG group) to 24 randomly selected controls (control group). Preoperative ultrasound biomicroscopy (UBM) metrics included anterior chamber depth (ACD), lens vault (LV), ciliary process distance (CCD), ciliary body thickness, anterior ciliary body placement, trabecular‒ciliary process angle (TCPA), and simulated cilio-lenticular distance (sCLD). To eliminate observer bias, all exported raw UBM images were completely anonymized, stripped of all identifiable metadata, randomized, and assigned unique computer-generated hashes before undergoing single-blinded evaluation. The MG group exhibited significantly shorter sCLD, greater LV, shallower ACD, and narrower TCPA preoperatively, with standardized mean differences exceeding 0.8. After False Discovery Rate correction, these differences remained significant (adjusted P < 0.05). Crucially, multivariable logistic regression adjusting for axial length (AL) demonstrated that a shortened sCLD (P < 0.001), an increased LV (P < 0.001), and a narrowed TCPA (adjusted P = 0.0099) maintained highly robust independent associations with MG development. The MG group showed a trend of weakened parameter coordination, particularly between AL and ACD (r = 0.334 vs. 0.718). Exploratory principal component analysis identified an architectural "anterior segment crowding" axis (explaining 62.2% of the variance), with the MG group clustering negatively. An exploratory, unweighted composite ciliary block score showed a large separation effect size (Cohen’s d = 1.995, P < 0.001). In conclusion, preoperative shortened sCLD, increased LV, and narrowed TCPA constitute an anatomical risk cluster independently associated with postoperative MG. While anterior segment crowding characterizes this cohort, these multivariate models function strictly as exploratory, sample-specific constructs and explicitly lack external clinical validation.

Introduction

Primary angle closure glaucoma (PACG) is a leading cause of irreversible blindness. It is particularly common in Asian populations, where anatomical predispositions to narrow anterior chamber angles are highly prevalent¹. These patients frequently suffer from elevated intraocular pressure. They often require surgical treatment to lower this pressure and prevent permanent optic nerve damage. Phacoemulsification combined with intraocular lens implantation and goniosynechialysis (PEI-GSL) is currently a highly effective surgical option. This procedure has demonstrated superior clinical efficacy in enlarging the anterior chamber angle, reducing dependency on topical glaucoma medications, and stabilizing long-term intraocular pressure fluctuations compared to alternative traditional options, such as laser peripheral iridotomy or laser peripheral iridoplasty². This procedure removes the thickened lens and separates the adhered anterior chamber angle. It effectively relieves pupillary block and opens the closed angle. However, while PEI-GSL offers significant clinical advantages over traditional filtering approaches (such as trabeculectomy) by lowering the incidence of prolonged postoperative hypotony, bleb-related infections, and early postoperative hyphema, it can sometimes lead to severe postoperative complications. Postoperative malignant glaucoma (MG) is one of the most challenging complications. Although rare, MG is a sight-threatening emergency. It is difficult to treat and often leads to treatment failure and severe visual impairment^3,4. Early identification and prevention are therefore extremely important for PACG patients undergoing this surgery.

The clinical course of MG is complex and notoriously difficult to manage. Its core pathophysiological process involves the abnormal reversal of aqueous flow. In a healthy eye, aqueous humor drains anteriorly through the trabecular meshwork. In MG, the aqueous humor misdirects and accumulates in the posterior vitreous cavity. This continuous fluid buildup causes a rapid increase in vitreous pressure. The elevated pressure then pushes the entire lens-iris diaphragm forward. This physical displacement results in a generalized shallowing or complete flattening of the anterior chamber, distinguishing it from typical pupillary block configurations where a peripheral iridotomy remains patent. It also causes extensive secondary angle closure and a sharp rise in intraocular pressure. These events form a self-sustaining vicious cycle^4,5,6. Traditionally, the occurrence of MG is closely linked to the concept of ciliary block. This mechanism suggests that the normal anatomical relationship among the ciliary body, crystalline lens, and anterior vitreous face is structurally disrupted. However, the exact anatomical risk factors for ciliary block remain unclear. We also lack precise preoperative predictive indicators. This lack of clarity creates significant challenges for early clinical identification and preventive surgical planning.

High-resolution imaging technologies have become essential tools for understanding these structural changes. Advances in ultrasound biomicroscopy (UBM) now allow for detailed measurements of the anterior segment. UBM can clearly visualize dark and hidden structures, including the ciliary body and the posterior chamber. This technology offers great potential for clarifying the anatomical basis of MG^7,8. Previous UBM studies indicate that a combination of certain macroscopic anatomical features creates a high-risk foundation for malignant glaucoma. These features typically include a short axial length and a very shallow anterior chamber. An anteriorly positioned lens and an abnormal anterior rotation of the ciliary body also contribute to this risk profile^9,10,11. Recently, researchers have introduced novel UBM parameters to improve risk assessment. The simulated cilio-lenticular distance (sCLD) is one such important parameter. It has gained significant attention in recent years. Researchers believe it may more directly reflect the localized risk of ciliary-lenticular block (ciliary block) compared to traditional global measurements¹².

The specific mechanistic role of these novel parameters in predicting MG has not been systematically investigated. Furthermore, their synergistic relationships with other key structural parameters require deeper exploration. Evaluating isolated parameters may not be enough to accurately predict surgical risks. A comprehensive assessment of anterior segment crowding might be necessary. Anterior segment crowding represents a macrolevel anatomical phenotype, and it is likely driven by the underlying ciliary block mechanism. Analyzing the structural coordination among various ocular parameters before surgery could provide deeper insights into the disease process. Therefore, this study aims to systematically deconstruct the anatomical basis of anterior segment crowding. We retrospectively compared detailed preoperative ocular parameters between PACG patients who developed MG after PEI-GSL and a control group who did not^12,13. Through this controlled comparison, we seek to identify potential high-risk anatomical features¹².

From a practical applicability perspective, this quantitative UBM screening approach offers clinicians a reproducible blueprint to stratify surgical risks and implement preventive management strategies before undergoing acute ocular decompression¹⁴. However, readers must acknowledge the clinical limitations inherent to this technique: UBM is highly operator-dependent, demands contact-shell immersion, which can be technically challenging or hazardous in exceptionally shallow anterior chambers, and restricts its evaluation to static anterior structures, thereby leaving out the potential hemodynamic or hydrostatic influences exerted by dynamic posterior vitreous and choroidal status^15,16. The ultimate goal of this research is to provide data-driven hypotheses regarding the pathological mechanisms of MG and establish reliable preoperative screening indicators for high-risk PACG patients^1,12.

Protocol

Formal institutional approval was obtained from the institutional Medical Ethics Committee before the initiation of the retrospective review. The investigation was conducted in strict accordance with the ethical principles of the Declaration of Helsinki. For the retrospective study design utilizing de-identified historical data, a waiver of informed consent was obtained from the oversight committee. Broad general consent for research utilization had been secured from patients at the time of their initial surgical admission.

1. Patient selection and cohort stratification

Case screening and group assignment
The institutional electronic medical record database was screened to identify all patients diagnosed with primary angle-closure glaucoma (PACG) who had undergone phacoemulsification, intraocular lens implantation, and goniosynechialysis (PEI-GSL) during the defined study period.

Establishment of the Malignant Glaucoma (MG) group
Records of patients who developed postoperative malignant glaucoma (MG) within three months following the primary surgery were extracted. Strict diagnostic criteria were applied, including persistent shallowing or complete flattening of both the central and peripheral anterior chamber, accompanied by normal or elevated intraocular pressure (IOP), in the presence of a patent peripheral iridotomy. The diagnosis was independently confirmed by two senior glaucoma specialists who were masked to subsequent volumetric analyses.

Establishment of the control group
A random sampling sequence (e.g., generated using a computer-generated random number table) was implemented to select control participants from the remaining pool of patients who had undergone identical PEI-GSL surgery during the same time frame by the same surgeon but did not exhibit signs of postoperative aqueous misdirection.

Eligibility and exclusion screening
Strict exclusion criteria were applied to all candidate records to minimize potential confounding factors. Excluded records included those with: (1) incomplete demographic, clinical, or imaging datasets; (2) a history of prior intraocular surgery or laser interventions; (3) intraoperative complications, including expulsive suprachoroidal hemorrhage, posterior capsular rupture, or intraoperative choroidal detachment; (4) secondary glaucoma configurations, such as neovascular, traumatic, uveitic, or exfoliative glaucoma, or primary open-angle glaucoma; and (5) coexisting structural anomalies, specifically nanophthalmos (defined as an axial length <20.0 mm) or lens subluxation.

2. Clinical baseline and preoperative examination procedures

Routine biometric assessment
Upon admission, standardized comprehensive ocular examinations were performed. Best-corrected visual acuity (BCVA) was documented using standard charts, and baseline intraocular pressure (IOP) was measured via Goldmann applanation tonometry. Detailed slit-lamp biomicroscopy was performed to verify anterior chamber depth and iris configuration. Optical biometry was conducted using an automated optical biometer to measure pre-surgical axial length (AL) via partial coherence interferometry.

Preoperative gonioscopy mapping
Dynamic and static gonioscopy were performed in a darkened room using a four-mirror gonioprism under minimal corneal pressure. The static narrow-angle configuration was documented according to the Scheie classification (Grades I–IV). To quantify peripheral anterior synechiae (PAS), gentle posterior pressure (compression gonioscopy) was applied to force open the recess, and the strict clock-hour extent of irreversible organic synechial angle closure across 360° was recorded.

Posterior segment screening
Spectral-domain optical coherence tomography (SD-OCT) scanning of the macula and optic disc was performed as part of the routine clinical protocol to assess the structural integrity of the retinal nerve fiber layer and to rule out comorbid vitreoretinal or macular pathologies. OCT-derived variables were excluded from subsequent predictive models of anterior segment crowding to maintain focus on local structural risk markers. Standard preoperative topical antimicrobial and fast-acting pressure-lowering medications were administered as clinically indicated.

3. Standardized surgical orchestration (PEI-GSL)

Anesthesia and incision architecture
Topical anesthesia was administered using topical ophthalmic anesthetic eye drops (0.5% proparacaine hydrochloride) three times before the procedure. The surgical field was sterilized and draped according to sterile ophthalmic protocols. A 2.2 mm main clear corneal tunnel incision was created at the temporal limbus, and a 1.0 mm side-port incision was created approximately 90° away using calibrated ophthalmic surgical blades.

Viscoelastic manipulation and goniosynechialysis
The anterior chamber was filled with a cohesive ophthalmic viscoelastic agent to deepen the space and maintain structural stability. A goniosynechialysis spatula was inserted through the side port under direct visualization through a surgical goniolens. The peripheral iris tissue was gently displaced posteriorly away from the trabecular meshwork. Mechanical dissection was performed across all clock hours exhibiting peripheral anterior synechiae until the scleral spur and trabecular meshwork were fully exposed.

Cataract extraction and intraocular lens implantation
A continuous curvilinear capsulorhexis approximately 5.0–5.5 mm in diameter was created. When pupil dilation was insufficient because of chronic synechiae, temporary pupil expansion devices were used to improve visualization. Standard phacoemulsification of the crystalline lens nucleus was performed using low-energy ultrasound parameters, followed by automated bimanual irrigation and aspiration of residual cortical material. A cohesive ophthalmic viscoelastic agent was injected to expand the capsular bag, and a foldable hydrophobic acrylic intraocular lens was implanted into the capsular bag. Residual viscoelastic material was then thoroughly aspirated from the anterior chamber and the retro-lens space.

Wound closure and postoperative medication management
The corneal stromal edges of the incisions were hydrated with balanced isotonic ophthalmic irrigation solution to achieve self-sealing wound closure. Structural watertight integrity was verified using the Seidel leakage test. At the conclusion of surgery, a combined antibiotic–corticosteroid ophthalmic ointment was applied. A standardized one-month postoperative topical regimen was maintained, consisting of combined antibiotic–corticosteroid ophthalmic drops (four times daily, tapered weekly), nonsteroidal anti-inflammatory ophthalmic drops (twice daily), and miotic ophthalmic drops containing 0.5% pilocarpine (twice daily) to stabilize the iris–lens diaphragm configuration.

4. Ultrasound biomicroscopy image acquisition settings

Instrument calibration and settings
High-frequency digital ultrasound biomicroscopy imaging was performed using a 50 MHz ultrasound biomicroscopy transducer. The electronic gain was set to 60–75 dB, with a scanning field of view of 14.0 mm × 10 mm and a scanning depth resolution of ≤50 µm. Prior to imaging, system calibration was verified using the manufacturer's automated electronic standard.

Scan execution and quality control checkpoints
Patients were positioned comfortably in the supine position under standardized mesopic lighting conditions (<5 lux). Patients were instructed to maintain steady fixation on a ceiling-mounted target. A sterile ophthalmic immersion eye cup was inserted into the conjunctival sac and filled with sterile physiological saline or 1% methylcellulose as an acoustic coupling medium. The high-frequency ultrasound probe was then gently immersed without applying mechanical pressure to the cornea.

Horizontal panoramic scan workflow
The probe was aligned horizontally across the vertical visual axis to obtain a panoramic cross-sectional image passing through the geometric center of the pupil. Image quality was considered acceptable only when the scleral spurs, iris contour, and anterior lens capsule were simultaneously and symmetrically visible on both the nasal and temporal sides of the image.

Radial quadrant scan workflow
Radial line scans were acquired at the 12, 3, 6, and 9 o'clock positions of the corneal limbus, corresponding to the superior, nasal, inferior, and temporal quadrants. At each location, the probe angle was adjusted until optimal acoustic alignment was achieved, as indicated by a distinct hyper-reflective scleral spur and clear visualization of the ciliary process apices. Images that did not meet these quality criteria were discarded and re-acquired.

5. Software-specific image measurement workflow

Image standardization and blinded randomization
Raw, uncompressed digital ultrasound biomicroscopy images were exported from the imaging system. To minimize assessor bias, all exported files were processed using an automated script that removed patient identifiers, randomized the image display order, and assigned a unique computer-generated cryptographic hash to each image. The randomized and blinded image set was subsequently provided to a single experienced glaucoma specialist for quantitative analysis.

Scale calibration and workspace setup
Images were opened in ImageJ. Spatial calibration was performed using the manufacturer's embedded calibration scale bar. A line corresponding to the known scale-bar length was defined, and the known distance and measurement unit (mm) were entered into the calibration settings. The calibration was applied globally to all images. Image contrast and brightness were standardized using fixed display settings to optimize visualization of anatomical boundaries.

Structural metric extraction and landmark resolution
Manual measurements were performed following predefined anatomical criteria.

Anterior Chamber Depth (ACD)
Anterior chamber depth was measured as the perpendicular distance between the central corneal endothelium and the anterior lens surface.

Lens Vault (LV)
A line connecting the nasal and temporal scleral spurs was established as the reference baseline. Lens vault was measured as the perpendicular distance from the anterior pole of the crystalline lens to the spur-to-spur baseline.

Ciliary Process–Ciliary Process Distance (CCD)
Using panoramic scans, the distance between the innermost ciliary process apex on one side and the corresponding apex on the opposite side was measured.

Ciliary body thickness boundary architecture
Radial quadrant scans were evaluated to identify the scleral spur and ciliary body boundaries. In regions affected by acoustic shadowing, measurements were referenced to the interface between the hyporeflective ciliary muscle tissue and the hyperreflective inner scleral wall.

Ciliary body thickness parameters
CBT0 was defined as the perpendicular distance from the scleral spur to the inner uveal border. CBT1000 was measured at a location 1000 µm posterior to the scleral spur along the inner scleral wall, with thickness determined perpendicular to the scleral surface. CBTmax was defined as the maximum thickness of the ciliary body adjacent to the ciliary process apex, measured perpendicular to the outer scleral surface.

Anterior Placement of the Ciliary Body (APCB)
A reference line perpendicular to the inner scleral wall was established at the scleral spur. APCB was measured as the perpendicular distance from the most anterior ciliary process apex to this reference line.

Trabecular–Ciliary Process Angle (TCPA)
The scleral spur served as the vertex of the angle. One arm extended along the inner border of the trabecular meshwork, while the second arm extended along the anterior surface of the ciliary process. The resulting angle was recorded in degrees.

Simulated Cilio-Lenticular Distance (sCLD)
A virtual tangent line passing through the scleral spur and oriented parallel to the outer scleral surface was established. The shortest distance from the ciliary process apex to this tangent line and the shortest distance from the anterior lens capsule to the same tangent line were measured. The difference between these measurements was recorded, with negative values retained when the ciliary process extended anteriorly beyond the lens plane.

For parameters obtained from quadrant-based measurements, values from the superior, nasal, inferior, and temporal quadrants were averaged to generate a single anatomical index for each eye.

6. Reproducible statistical analysis workflow

Package deployment and environment initialization
All computational and statistical analyses were performed in the R environment (version 4.5.1). The analytical workflow incorporated the tidyverse suite, including the ggplot2 package for data visualization, the stats package for statistical modeling, and the factoextra package for principal component analysis visualization. A significance level of α = 0.05 was adopted for all statistical tests.

Univariate and covariate adjustment analysis
Data distributions were assessed using the Shapiro–Wilk test. Variables exhibiting normal distributions were compared using independent two-sample t-tests assuming equal variances, whereas non-normally distributed variables were analyzed using the Mann–Whitney U test.

Multiple testing correction
To account for multiple simultaneous ultrasound biomicroscopy parameter comparisons, p-values were adjusted using the Benjamini–Hochberg false discovery rate procedure. Adjusted q-values < 0.05 were considered statistically significant.

Standardized mean differences
Standardized mean differences were calculated to assess group balance.

Multivariable logistic regression
Multivariable logistic regression models were constructed to identify independent predictors while controlling for potential confounding variables. Axial length was included as a covariate, and Wald statistics were used to evaluate predictor significance.

Multivariate coordination and pattern clustering
Pearson correlation coefficients were calculated to assess relationships among key biometric parameters. Correlation coefficients were subsequently transformed using Fisher’s z-transformation to evaluate differences in inter-parameter coordination between study groups.

Principal component analysis
Quantitative variables were standardized using the Z-score transformation prior to analysis. Principal component analysis was performed to characterize multivariate structural patterns and evaluate group separation. Variable loadings and participant projections were extracted and visualized using principal component analysis visualization tools.

Composite scoring framework
An unweighted composite ciliary block score was calculated using standardized values of simulated cilio-lenticular distance, trabecular–ciliary process angle, and lens vault. The directionality of simulated cilio-lenticular distance and trabecular–ciliary process angle was reversed such that higher values consistently reflected increased anatomical risk. The composite score was obtained by summing the aligned standardized metrics for each participant.

Results

As shown in Table 1, there were no significant differences in demographic characteristics or biometric parameters between the MG and control groups. Crucially, the Standardized Mean Difference (SMD) for essential baseline covariates, such as axial length (AL) (SMD = 0.232) and age (SMD = 0.298), was well below the 0.3 threshold, establishing robust balance in these measured baseline variables between the cohorts. However, significant anatomical differences were observed in the UBM parameters (

Discussion

Malignant glaucoma (MG) remains a highly challenging clinical problem in diagnosis and treatment, and improving its identification is crucial for preserving patients’ visual function. Although ciliary block is traditionally considered the key mechanism leading to aqueous misdirection, as documented across modern literature^11,12,17, reliable preoperative predictive indicators have remained elusive. This study provides clini...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Automated Optical Biometer	Carl Zeiss Meditec AG	IOLMaster 500	Partial coherence interferometry ocular axial length biometry device
Bromfenac Sodium Drops	Bausch & Lomb Inc.	Prolensa 0.07%	Topical non-steroidal anti-inflammatory ophthalmic eye drops
Disposable Immersion Eye Cup	Tianjin Suowei Electronic Technology Co., Ltd.	SEC-140	Sterile plastic shell coupling sleeve for contact high-frequency UBM scanning
effsize Package	CRAN Repository	Version 0.8.1	R package for calculating Standardized Mean Differences and Cohen’s d
factoextra Package	CRAN Repository	Version 1.0.7	Specialized R toolkit for principal component matrix visualization
ggplot2 Package	Posit, PBC (CRAN)	Version 3.5.0	High-performance R data package for advanced scatter plotting
Goniosynechialysis Spatula	Katena Products, Inc.	K3-2520	Specialized microsurgical spatula for posterior mechanical iris dissection
Hydrophobic Acrylic IOL	Alcon Laboratories, Inc.	AcrySof IQ SN60WF	Foldable single-piece hydrophobic acrylic intraocular lens
ImageJ Software	National Institutes of Health	Version 1.54h	Open-source Java-based image processing and multi-parameter calibration tool
Methylcellulose Gel	Novartis AG	OcuCoat 2%	1% ophthalmic clear viscoelastic gel serving as acoustic coupling medium
Phacoemulsification Knife	BD Medical - Ophthalmic Systems	372222	2.2 mm calibrated clear corneal tunnel slit incision blade
Phacoemulsification System	Alcon Laboratories, Inc.	Centurion Vision System	Microsurgical cataract extraction platform with low-energy ultrasound parameters
Pilocarpine Hydrochloride Drops	Novartis AG	Isopto Carpine 0.5%	0.5% topical miotic parasympathomimetic iris diaphragm stabilizer
Proparacaine Hydrochloride	Alcon Laboratories, Inc.	NDC 0065-0251-15	0.5% topical ophthalmic anesthetic drops for surface desensitization
psych Package	CRAN Repository	Version 2.4.3	R suite for executing Fisher's z-transformation correlation testing
R Statistical Environment	R Foundation for Statistical Computing	Version 4.5.1	Computational language engine for multivariate modeling and data scaling
Side-Port Knife	BD Medical - Ophthalmic Systems	371015	1.0 mm side-port paracentesis angled incision blade
Sodium Hyaluronate	Bausch & Lomb Inc.	Amvisc Plus 1.6%	Cohesive viscoelastic agent for anterior chamber deepening and stabilization
Spectral-Domain OCT	Heidelberg Engineering GmbH	Spectralis HRA+OCT	Optical coherence tomography scanner for retinal nerve fiber layer screening
tidyverse Package Suite	Posit, PBC (CRAN)	Version 2.0.0	R package matrix for data manipulation and advanced functional piping
Tobramycin-Dexamethasone Drops	Alcon Laboratories, Inc.	TobraDex 5mL	Combined topical post-surgical anti-inflammatory steroid eye drops
Tobramycin-Dexamethasone Ointment	Alcon Laboratories, Inc.	TobraDex Sterile	Combined antibiotic-corticosteroid post-surgical ophthalmic ointment
Ultrasound Biomicroscopy System	Tianjin Suowei Electronic Technology Co., Ltd.	SW-3200L	High-frequency digital 50 MHz anterior segment acoustic imaging scanner