May 2019
Volume 60, Issue 6
Open Access
Glaucoma  |   May 2019
Anterior Segment Features in Nanophthalmos With Secondary Chronic Angle Closure Glaucoma: An Ultrasound Biomicroscopy Study
Author Affiliations & Notes
  • Congcong Guo
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Zhenni Zhao
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Dandan Zhang
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Jiafan Liu
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Jianlong Li
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Jiamin Zhang
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Nannan Sun
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Denghui Chen
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Miao Zhang
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Zhigang Fan
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Correspondence: Zhigang Fan, State Key Laboratory of Ophthalmology, Department of Glaucoma, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 Xianlie South Road, Guangzhou 510060, China; fanzhg3@mail.sysu.edu.cn
  • Footnotes
     CG and ZZ contributed equally to the work presented here and should therefore be regarded as equivalent authors.
Investigative Ophthalmology & Visual Science May 2019, Vol.60, 2248-2256. doi:https://doi.org/10.1167/iovs.19-26867
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      Congcong Guo, Zhenni Zhao, Dandan Zhang, Jiafan Liu, Jianlong Li, Jiamin Zhang, Nannan Sun, Denghui Chen, Miao Zhang, Zhigang Fan; Anterior Segment Features in Nanophthalmos With Secondary Chronic Angle Closure Glaucoma: An Ultrasound Biomicroscopy Study. Invest. Ophthalmol. Vis. Sci. 2019;60(6):2248-2256. doi: https://doi.org/10.1167/iovs.19-26867.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: We compare anterior segment parameters and the risk of malignant glaucoma between nanophthalmos with secondary chronic angle closure glaucoma (NSCACG) and chronic primary angle-closure glaucoma (CPACG).

Methods: This retrospective case-control study included 32 NSCACG (32 eyes) and 36 CPACG (36 eyes) patients. Anterior segment parameters, including anterior chamber depth (ACD) and width (ACW), pupil diameter (PD), lens vault (LV), ciliary process-ciliary process distance (CCD), angle opening distance500 (AOD500), trabecular-iris angle (TIA), trabecular-ciliary processes distance (TCPD), ciliary body max thickness (CBMT), iris convexity (IC), peripheral iris thickness (PIT), iris-zonule distance (IZD), trabecular ciliary process angle (TCPA), and anterior vault (AV), were measured by ultrasound biomicroscopy. A-scan ultrasonography measurements, including lens thickness (LT) and axial length (AL), also were reviewed.

Results: ACD, ACW, CCD, TCPD, and AL were smaller, whereas the LV, LT/AL, LV/LT, LV/ACD, LT/ACD, LV/AV, and AV/AL were larger in NSCACG compared to CPACG eyes (all Bonferroni-corrected P < 0.05). Eyes with NSCACG had a higher risk of malignant glaucoma postoperatively than eyes with CPACG (P = 0.018).

Conclusions: Characterized by narrower anterior segment, forward movement of larger lens, more anteriorly rotated ciliary bodies, and smaller CCD, NSCACG eyes have a higher risk of malignant glaucoma than CPACG eyes.

Nanophthalmos is defined as a small eye without other ocular or systemic malformations. During 7 weeks to 8 months of embryonic phase in nanophthalmos patients, there seems to be an arrest in eye growth after closure of the embryonic cleft.1 Consequently, the nanophthalmos has several anatomic characters, such as short axial length (AL), shallow anterior chamber depth (ACD) and thick sclera.24 In addition, nanophthalmic patients are prone to have a chronic, painless type of angle closure glaucoma in middle age due to the natural increase in size of the lens.5,6 
The anterior segment in eyes with nanophthalmos and secondary chronic angle closure glaucoma (NSCACG) is similar to that in eyes with chronic primary angle closure glaucoma (CPACG), but it might be more like an extreme form of CPACG. The high risk of surgical complications in NSCACG patients often is attributed to their unique anatomic structure. Many studies have reported that the thick and dense sclera would limit the ophthalmic venous reflux, resulting in a thick choroid and leading to surgical complications, such as uveal effusion.3,7 However, few studies focused on its crowded anterior segment,8 which might be associated with malignant glaucoma, a severe surgical complication.9 Possible risk factors for malignant glaucoma that have been postoperatively validated by other studies are axial shallowing ACD, anterior rotation of the ciliary body, and a small ciliary ring.1012 
The ocular anterior segment can be observed clearly through ultrasound biomicroscopy (UBM). This relatively objective and reproducible examination provides cross-sectional images of the chamber angle, profile of the iris and posterior chamber, and size and position of the ciliary body.13,14 Many structural parameters can be measured precisely using the special caliper within the UBM instrument.15,16 
To identify features of the anterior segment in eyes with NSCACG and analyze which group has the higher risk of malignant glaucoma under the stimuli of surgeries, we compared the UBM-measured anterior segment parameters between NSCACG and CPACG patients. 
Methods
This retrospective case-control study included patients diagnosed with NSCACG by two glaucoma specialists (Z.F. and Z.Z.) between May 2012 and March 2017 in Zhongshan Ophthalmic Center (ZOC) affiliated with Sun Yat-sen University (China) and patients with CPACG randomly selected during the same period using random number tables. This study adhered to the tenets of the Declaration of Helsinki and was approved by the human research ethics committee in ZOC. Informed consent was exempted for this retrospective study. 
The diagnosis of NSCACG was based on the following criteria: (1) characters of nanophthalmos including short AL less than 20 mm and without morphologic malformation; (2) in combination with secondary chronic angle closure glaucoma because of the relatively thickened lens without other reasons, such as trauma, uveitis, neovascularization or increased episcleral venous pressure; and (3) without symptoms and signs of acute angle closure attack, such as severe distending pain with nausea and/or vomiting, sudden blurred vision, emergence of glaukomflecken or iris sphincter palsy. On the other side, primary angle closure (PAC) was defined as an eye with at least 180° iridotrabecular contact with peripheral anterior synechiae or elevated IOP, but without glaucomatous optic neuropathy or visual field defect. CPACG is defined as the presence of PAC with evidence of optic nerve damage and glaucomatous visual field defect caused by relatively high IOP, but without symptoms and signs of acute angle closure attack. Patients with iris and ciliary body condition influenced by local or systemic mydriatics, miotics, or hyperosmotic agents, or patients without UBM examination or with blurred UBM image (assessed based on corneal reflection, indeterminate scleral spurs, continuity of anterior segment structures, and motion artifacts) were excluded. 
All patients received a comprehensive ocular examination including the best-corrected visual acuity (BCVA) measured with the Snellen chart and converted into a logMAR equivalent, IOP measured with a Goldmann applanation tonometer, anterior segment examined with slit-lamp microscopy, anterior chamber angle examined in the dark using gonioscopy at high magnification, ocular fundus examined with a 90 diopter (D) preset lens and optical coherence tomography (OCT; Heidelberg Engineering, Heidelberg, Germany), lens thickness (LT) and AL measured with a A-scan ultrasonic biometry (Model KN-3000A; Quantel Co Ltd., Clermont-Ferrand, France), and visual field measured with Humphrey perimetry (Carl Zeiss Meditec, Dublin, CA, USA). In addition, the number of antiglaucoma medications was recorded. 
Ultrasound Biomicroscopy
The UBM (model SW-3200L; Tianjin Suowei Electronic Technology Co., Ltd., Tianjin, China) was performed on these patients at the initial consultation in ZOC by a trained physician (XC). The UBM was equipped with a single element mechanical linear scanner and its frequency of the probe transducer was 50 MHz. Patients were examined in a dimly lit room (illumination 60–70 lux, model TES-1339; TES Electrical Electronic Corp, Tianjin, China) in a supine position. Radial scan (big image mode) was performed at the 12, 3, 6, and 9 o' clock positions centered over the limbus, corresponding to the superior, nasal, inferior, and temporal quadrants in the right eye and superior, temporal, inferior, and nasal quadrants in the left eye, respectively. Additionally, perpendicular sulcus-to-sulcus scans (small image mode) were conducted over the pupil center. Up to100 images could be stored as cache in this equipment at a speed of five images per second when conducting anterior segment scanning. Then, the best images were chosen by an experienced glaucoma specialist (ZZ) who was masked to the clinical information. The scan must be centered on the pupil or over the limbus, be well circumscribed, and show the scleral process, corneal epithelium/endothelium, iris pigment epithelium, and anterior lens capsule as clearly as possible. The selected images were stored in the equipment (an example is shown in Fig. 1). 
Figure 1
 
UBM images of eyes with NSCACG and CPACG. Arrow indicates the location of scleral spur.
Figure 1
 
UBM images of eyes with NSCACG and CPACG. Arrow indicates the location of scleral spur.
The following UBM parameters of the anterior segment were examined by the built-in caliper in the equipment. The definitions of these quantitative parameters (Fig. 2) were: 
  1.  
    ACD is measured from the corneal endothelium to the anterior lenticular surface centered over the pupil;17
  2.  
    Pupil diameter (PD) is the distance between the pupil edges on the center cross-sectional images;18
  3.  
    Anterior chamber width (ACW) is the horizontal scleral spur-to-spur distance;19
  4.  
    Lens vault (LV) is the perpendicular distance between the anterior pole of the lens and the horizontal line joining the two scleral spurs;20
  5.  
    Ciliary process-ciliary process distance (CCD), corresponding to the ciliary ring diameter, is the maximum distance between the apex of ciliary process on the center cross-sectional images;21
  6.  
    Angle opening distance500 (AOD500) is the distance between the inner corneal surface and the anterior iris surface measured on a line perpendicular to the plane of the trabecular meshwork at 500 μm from the scleral spur;17
  7.  
    Trabecular-iris angle (TIA) is measured with its apex at the scleral spur and the arms of the angle passing through a point on the trabecular meshwork at 500 μm from the scleral spur and the point on the anterior surface of the iris perpendicularly opposite;17
  8.  
    Trabecular-ciliary processes distance (TCPD) is measured as a line extending from the trabecular meshwork at 500 μm from the scleral spur perpendicularly through the iris to the surface of ciliary process;17
  9.  
    Ciliary body max thickness (CBMT) is the distance from the most inner point of the ciliary body perpendicular to the inner surface of the sclera or its extended line;17
  10.  
    Iris convexity (IC) is the perpendicular distance between the greatest convexity point of the iris pigment epithelium and the line joining the most peripheral to the most central points of iris pigment epithelium (the distance value is positive when the iris is convex anteriorly, but negative when iris is convex posteriorly);18
  11.  
    Peripheral iris thickness (PIT) is the iris thickness along the same line of TCPD;17
  12.  
    Iris-zonule distance (IZD), corresponding to the posterior chamber depth (PCD), is the distance between the posterior iris surface to the first visible zonule fiber at the point just clearing the ciliary process, along with the same line of TCPD;17
  13.  
    Trabecular ciliary process angle (TCPA) is measured with its apex at the scleral spur, one arm along the posterior corneal surface, and another arm along the most anterior surface of the ciliary body.17
Figure 2
 
UBM measurement parameters of anterior segment. (A) ACD, PD, ACW, LV, CCD. (B) AOD500, TIA, CBMT, IC. (C) TCPD, PIT, IZD, TCPA. UBM, ultrasound biomicroscopy.
Figure 2
 
UBM measurement parameters of anterior segment. (A) ACD, PD, ACW, LV, CCD. (B) AOD500, TIA, CBMT, IC. (C) TCPD, PIT, IZD, TCPA. UBM, ultrasound biomicroscopy.
The ACD value was obtained through the UBM software automatically. The other UBM parameters were measured manually three times and the median values were recorded. The parameters, including AOD500, TIA, TCPD, CBMT, IC, PIT, IZD, and TCPA measured in the superior, nasal, inferior, and temporal direction were averaged and recorded. In addition, five previously reported parameters2224 (anterior vault [AV], ACD + LV; relative AV, AV/AL; relative LV, LV/AV; relative ACD, ACD/AL; relative anterior chamber position, LT/ACD) and three novel parameters (relative anterior chamber position, LV/ACD; relative lens position, LV/LT; relative iris thickness, PIT/TCPD) were calculated. 
Malignant Glaucoma After Intraocular Surgery
Twenty-four of 32 NSCACG eyes and 34 of 36 CPACG eyes had undergone surgeries. Malignant glaucoma was diagnosed based on the presence of a shallow or flat anterior chamber, increased IOP, presence of a patent peripheral iridotomy, and absence of posterior segment pathology (choroidal effusion or suprachoroidal hemorrhage). 
Statistical Analyses
Statistical analyses were conducted using SPSS version 20 (SPSS, Inc., Chicago, IL, USA). The left eye in each subject was selected for analyses. However, the right eye data were used when the left eye did not meet inclusion criteria. Parameters between the NSCACG and CPACG groups were compared using the independent t-test or the Mann-Whitney U test according to the distribution of the data. Stepwise multivariable linear regression was used to identify biometric measurements associated with TCPD, after adjusting for age, BCVA, and IOP. Multicollinearity among explanatory variables was detected using variance inflation factors (VIF). The difference in malignant glaucoma after intraocular surgery between NSCACG and CPACG patients was analyzed by the χ2 test. Receiver operating characteristic (ROC) analysis was performed on UBM parameters to identify area under the curve (AUC) and optimal thresholds for malignant glaucoma. All multiple testings were adjusted by Bonferroni correction. P < 0.05 was considered statistically significant. 
To evaluate intraobserver reproducibility, 15 images from recruited subjects were selected randomly and the anterior segment parameters were remeasured by the same experienced glaucoma specialist (ZZ) on two separate occasions. The intraobserver reproducibility was estimated with an intraclass correlation coefficient (ICC). 
Results
Excluding five NSCACG and 10 CPACG eyes due to low-quality UBM images, a total of 32 eligible eyes from 32 NSCACG subjects and 36 eligible eyes from 36 CPACG subjects were reviewed. The demographics, BCVA, IOP, number of antiglaucoma medications, extent of peripheral anterior synechiae (PAS), ratio of cup to disc (C/D), the mean deviation (MD), and pattern standard deviation (PSD) of the visual field at initial consultation in ZOC are listed in Table 1. NSCACG patients were younger than CPACG patients (P < 0.001), and there was no sex difference between the two groups (P = 0.418). The BCVA was worse, whereas the C/D ratio was lower in NSCACG than in CPACG eyes (P < 0.001; P = 0.004). There were no significant differences in IOP, number of antiglaucoma medications, extent of PAS, MD, and PSD between these two groups (all P > 0.05). 
Table 1
 
Demographics and Basic Clinical Data of Recruited Eyes
Table 1
 
Demographics and Basic Clinical Data of Recruited Eyes
Table 2 summarizes the comparisons of biometric measurements detected by UBM and A-scan between NSCACG and CPACG. Twelve measurements showed differences between the two groups at a Bonferroni level of significance. ACD, ACW, CCD, TCPD, and AL were smaller, whereas LV, LT/AL, LV/LT, LV/ACD, LT/ACD, LV/AV, and AV/AL were larger in NSCACG compared to CPACG eyes (all Bonferroni-corrected P < 0.05). Figure 3 and Supplementary Table S1 show the comparisons of AOD500, TIA, TCPD, CBMT, IC, PIT, IZD, and TCPA in all quadrants between the two groups. After Bonferroni correction, TCPD was significantly smaller in the nasal and temporal quadrants (P = 0.004, P < 0.001) and TCPA was significantly narrower in the nasal quadrant (P = 0.008) in NSCACG eyes than in CPACG eyes. 
Table 2
 
Comparison of Biometric Measurements of Recruited Eyes Between NSCACG and CPACG
Table 2
 
Comparison of Biometric Measurements of Recruited Eyes Between NSCACG and CPACG
Figure 3
 
Comparisons of AOD500, TIA, TCPD, CBMT, IC, PIT, IZD, TCPA in all quadrants between eyes with NSCACG and CPACG. *Bonferroni-corrected P < 0.05. Error bars: 95% CI.
Figure 3
 
Comparisons of AOD500, TIA, TCPD, CBMT, IC, PIT, IZD, TCPA in all quadrants between eyes with NSCACG and CPACG. *Bonferroni-corrected P < 0.05. Error bars: 95% CI.
In the stepwise multivariable linear regression, ACD/AL and AL were positively associated with TCPD (P = 0.026, P = 0.001), respectively (Table 3). There was no evidence for multicollinearity, since all VIF values were <10. 
Table 3
 
Multivariable Linear Regression Analysis to Identify the Association Between Biometric Measurements and TCPD
Table 3
 
Multivariable Linear Regression Analysis to Identify the Association Between Biometric Measurements and TCPD
The surgery types and development of malignant glaucoma in NSCACG and CPCAG patients are detailed in Table 4. The NSCACG eyes had a higher risk of malignant glaucoma postoperatively than CPACG eyes (37.5% vs. 8.8%; odds ratio [OR], 6.20; 95% confidence interval [CI], 1.46–26.29; P = 0.018). The χ2 test showed a significant difference in surgical types between the two groups (P < 0.001). The most common surgeries were surgical peripheral iridectomy (54.2%) and phacoemulsification (25.0%) in NSCACG patients, and trabeculectomy (58.8%), phacotrabeculectomy (14.7%), and surgical peripheral iridectomy (14.7%) in CPACG patients. The incidence of malignant glaucoma for each operation in each group also is shown in Table 4. Although phacotrabeculectomy had the lowest incidence of malignant glaucoma (0.0%), there was no significant association between surgical types and the occurrence of malignant glaucoma (P = 0.132), whether in NSCACG (P = 0.051) or in CPACG (P = 0.340) patients. No significant difference of the time intervals between the surgeries and development of malignant glaucoma between NSCACG (113.25 ± 74.82 days) and CPACG (100.33 ± 70.47 days) patients was observed (P = 0.802). 
Table 4
 
The Surgical Types and the Incidence of Malignant Glaucoma in NSCACG and CPCAG Patients
Table 4
 
The Surgical Types and the Incidence of Malignant Glaucoma in NSCACG and CPCAG Patients
To investigate which parameters were associated with malignant glaucoma postoperatively, the parameters were compared between patients with and without malignant glaucoma in the NSCACG and CPACG groups, respectively (Table 5). No parameters were associated with malignant glaucoma in NSCACG patients. However, four parameters had connections with malignant glaucoma occurrence in CPACG patients. CPACG patients with larger IC, LV/ACD, and LT/ACD and smaller PIT were prone to suffer malignant glaucoma (all P < 0.05). Figure 4 shows the ROC curves for these parameters among the CPACG patients for identification of malignant glaucoma cases. The AUCs and optimal thresholds of UBM parameters for malignant glaucoma in CPACG patients are shown in Table 6. The AUC ranged from 0.94 to 1.00, with PIT showing the greatest diagnostic power. 
Table 5
 
Comparison of Parameters Between Patients With and Without Malignant Glaucoma After Intraocular Surgeries in NSCACG and CPACG Groups
Table 5
 
Comparison of Parameters Between Patients With and Without Malignant Glaucoma After Intraocular Surgeries in NSCACG and CPACG Groups
Figure 4
 
ROC curves for parameters to separate malignant glaucoma from CPACG patients.
Figure 4
 
ROC curves for parameters to separate malignant glaucoma from CPACG patients.
Table 6
 
Result of ROC Analysis in CPACG Patients
Table 6
 
Result of ROC Analysis in CPACG Patients
Table 7 lists the intraobserver reproducibility of UBM parameters measurements in a randomly selected subset of 15 eyes. All parameters verified excellent reproducibility with ICCs (all ICC > 0.90). 
Table 7
 
Reproducibility of UBM Parameters of Anterior Segment in a Random Subset of Eyes
Table 7
 
Reproducibility of UBM Parameters of Anterior Segment in a Random Subset of Eyes
Discussion
Short AL and narrow anterior chamber with the gradual growth of LT are the main causes of secondary chronic angle closure glaucoma in nanophthalmic eyes.3 In the current study, symptoms and signs of NSCACG were similar to those of CPACG, such as gradually blurred vision without obvious ocular pain, anterior chamber angle adhesion, high IOP, optic nerve damage, and visual field defect. Although many studies verified that the anterior segment in NSCACG eyes was narrower than that in normal eyes,3,8,25 to date little is known about the quantitative comparisons, including biometric measurements and the occurrence of malignant glaucoma, between NSCACG and CPACG eyes. To this end, we designed and conducted this study. 
In the present study, the anterior segment in the NSCACG eyes was more crowded than that in CPACG eyes, and this was validated through the following points: (1) ACW, which corresponds to spur-spur distance, implies a smaller anterior chamber volume and indicates a risk of angle closure.19,26 In our study, the ACW and ACD were lower in NSCACG eyes than in CPACG eyes; (2) The increased LV was thought to be associated with angle closure in a clinical research by Monisha et al.,20 who found that the increased LV would enlarge contact area between the lens and iris, promoting a narrow or even closed anterior chamber angle. In this study, compared to CPACG eyes, NSCACG eyes showed larger LV, suggesting a smaller anterior chamber angle. (3) Additionally, two novel calculated parameters (LV/LT and LV/ACD) and four reported calculated parameters (LT/AL, LV/AV, LT/ACD, and AV/AL)22,24,27 were larger in NCSACG than in CPACG eyes, indicating the forward movement of enlarged lens and the narrow anterior chamber. In a word, our study proved the extremely crowded anterior segment in NSCACG eyes, which had a higher incidence of malignant glaucoma postoperatively than did CPACG eyes. 
CCD also is called “ciliary ring diameter” reflecting the ciliary ring size.21 In the current research, the CCD in the eyes with NSCACG was smaller than in eyes with CPACG. Two possible pathogenesis mechanisms underly this phenomenon: (1) due to the developmental eyeball defect, the small eye volume leads to the small CCD; (2) because of high hyperopia in nanophthalmos, ciliary spasm induced by excessive accommodation causes small CCD. On the other hand, the lens gradually loses elasticity and its equatorial diameter increases with growth during aging.28 Therefore, due to a combination of small CCD and increased hardness and volume of the lens, middle-aged patients with NSCACG would tend to have ciliary ring block, especially in surgeries with an unstable anterior chamber. This study also illustrates that, during surgery, the eyes with NSCACG have higher risk factors for malignant glaucoma. 
No significant differences in PIT and IC were observed between NSCACG and CPACG patients. However, we found that PIT and IC had high diagnosis power for malignant glaucoma in CPACG patients. Several mechanisms have been delineated to explain the cause of malignant glaucoma.2932 The key lies in the lack of forward movement of the aqueous due to the anterior rotation of the ciliary processes against the lens equator (ciliolenticular block) in phakic or the anterior hyaloid face (ciliovitreal) in aphakic or pseudophakic eyes, which leads to the difference of pressures in the posterior and anterior chambers.32 By UBM studies, anterior rotation of the ciliary body has been identified as the main anatomic change in eyes with malignant glaucoma.11,16 The pressure differential causes anterior convexity of the iris and shallowing of the anterior chamber. Huang et al.33 reported that the thinned and floppy iris was more prone to positional changes influenced by aqueous currents. Our study firstly reported that PIT and IC had the diagnostic power for malignant glaucoma in CPACG patients, and the optimal thresholds for these two parameters were identified (PIT ≤ 0.29 mm, IC ≥ 0.33 mm). A disproportionately large lens in nanophthalmos leads to increased ciliolenticular apposition, which probably explains the higher malignant glaucoma tendency in these eyes.34 Moreover, LV/ACD and LT/ACD could be used to identify malignant glaucoma in CPACG patients. For ruling in malignant glaucoma, the optimal LV/ACD threshold value of ≥ 0.55 had a sensitivity of 100% and specificity of 81%, and the optimal LT/ACD threshold value of ≥ 2.89 had a sensitivity of 100% and specificity of 87%. The PS Power and Sample Size Calculations V3.0 was used to detect the expected statistical power, presenting the probability that the tests correctly reject the null hypothesis when the alternative hypothesis is true.35 The level of significance was set at 0.05. The powers to detect the association between IC, PIT, LV/ACD, LT/ACD, and the occurrence of malignant glaucoma were 0.899, 0.922, 0.878, and 0.868, respectively. All powers were over 0.80, which suggested the relative reliability of our study on addressing the associations between parameters and the occurrence of malignant glaucoma in CPACG patients. For NSCACG patients, although eyes with malignant glaucoma had relatively smaller AL, ACW, ACD, CCD, and relative larger LV compared to eyes without malignant glaucoma, no UBM parameters were observed to be associated with malignant glaucoma in NSCACG patients, resulting partly from the limited number of sample size. The modest anatomical differences in NSCACG patients could be studied by further large-scale cohort research. 
Shorter TCPD, reflecting the position of ciliary bodies, was associated with the more anteriorly rotated ciliary body.33,36 Wang et al.16 reported that more anteriorly rotated ciliary body and greater LV may predispose to malignant glaucoma, which was verified by our study. Furthermore, AL and ACD/AL were positively correlated with TCPD in our study, based on stepwise multivariable linear regression. The smaller ACD/AL and the shorter AL were connected with the more anteriorly located ciliary body, which might be the anatomic contributing factors for the occurrence of malignant glaucoma. Therefore, one should be more cautious when conducting antiglaucoma surgeries on patients with smaller ACD/AL and shorter AL. 
Our study, however, has several limitations. Firstly, systemic errors in distance measurements from the ultrasound digital image were inevitable. Secondly, the manual localization of the anatomic landmark scleral spur was subjective, but in our study the researcher was blinded to the patients' clinical information to avoid bias. Additionally, the reproducibility test was conducted on two separate occasions by the same ophthalmologist. Thirdly, antiglaucoma medications used in the recruited subjects might have influenced our measurements. Fourthly, the sample size was not large and further large-scale cohort study is needed. 
In summary, our study demonstrated that NSCACG eyes with a narrower anterior segment, forward movement of a larger lens, more anteriorly rotated ciliary bodies, and smaller CCD are at higher risk for malignant glaucoma than CPACG eyes when undergoing antiglaucoma surgeries. Specifically, performing surgery on eyes with CPACG should be done more carefully in cases of smaller PIT, larger IC, LT/ACD, and LV/ACD. Further investigation of the incidence rate of malignant glaucoma after surgeries in two groups with a larger sample size may provide more powerful evidence into this finding. 
Acknowledgments
The authors thank Xiaoyu Cai for conducting the UBM test on the patients in this study. 
Supported by the Major Project of National Natural Science Foundation of China (NSFC)-Guangdong Province Joint Fund (Grant 3030902113080), the Science and Technology Planning Project of Guangdong Province (Grant 303090100502050-18), Research Funds of the State Key Laboratory of Ophthalmology (Grants 30306020240020153, 30306020240020192, 3030902113058, 3030902113118, PT1001022), and Fundamental Research Funds of Sun Yat-sen University (Grant 16ykjc31). 
Disclosure: C. Guo, None; Z. Zhao, None; D. Zhang, None; J. Liu, None; J. Li, None; J. Zhang, None; N. Sun, None; D. Chen, None; M. Zhang, None; Z. Fan, None 
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Figure 1
 
UBM images of eyes with NSCACG and CPACG. Arrow indicates the location of scleral spur.
Figure 1
 
UBM images of eyes with NSCACG and CPACG. Arrow indicates the location of scleral spur.
Figure 2
 
UBM measurement parameters of anterior segment. (A) ACD, PD, ACW, LV, CCD. (B) AOD500, TIA, CBMT, IC. (C) TCPD, PIT, IZD, TCPA. UBM, ultrasound biomicroscopy.
Figure 2
 
UBM measurement parameters of anterior segment. (A) ACD, PD, ACW, LV, CCD. (B) AOD500, TIA, CBMT, IC. (C) TCPD, PIT, IZD, TCPA. UBM, ultrasound biomicroscopy.
Figure 3
 
Comparisons of AOD500, TIA, TCPD, CBMT, IC, PIT, IZD, TCPA in all quadrants between eyes with NSCACG and CPACG. *Bonferroni-corrected P < 0.05. Error bars: 95% CI.
Figure 3
 
Comparisons of AOD500, TIA, TCPD, CBMT, IC, PIT, IZD, TCPA in all quadrants between eyes with NSCACG and CPACG. *Bonferroni-corrected P < 0.05. Error bars: 95% CI.
Figure 4
 
ROC curves for parameters to separate malignant glaucoma from CPACG patients.
Figure 4
 
ROC curves for parameters to separate malignant glaucoma from CPACG patients.
Table 1
 
Demographics and Basic Clinical Data of Recruited Eyes
Table 1
 
Demographics and Basic Clinical Data of Recruited Eyes
Table 2
 
Comparison of Biometric Measurements of Recruited Eyes Between NSCACG and CPACG
Table 2
 
Comparison of Biometric Measurements of Recruited Eyes Between NSCACG and CPACG
Table 3
 
Multivariable Linear Regression Analysis to Identify the Association Between Biometric Measurements and TCPD
Table 3
 
Multivariable Linear Regression Analysis to Identify the Association Between Biometric Measurements and TCPD
Table 4
 
The Surgical Types and the Incidence of Malignant Glaucoma in NSCACG and CPCAG Patients
Table 4
 
The Surgical Types and the Incidence of Malignant Glaucoma in NSCACG and CPCAG Patients
Table 5
 
Comparison of Parameters Between Patients With and Without Malignant Glaucoma After Intraocular Surgeries in NSCACG and CPACG Groups
Table 5
 
Comparison of Parameters Between Patients With and Without Malignant Glaucoma After Intraocular Surgeries in NSCACG and CPACG Groups
Table 6
 
Result of ROC Analysis in CPACG Patients
Table 6
 
Result of ROC Analysis in CPACG Patients
Table 7
 
Reproducibility of UBM Parameters of Anterior Segment in a Random Subset of Eyes
Table 7
 
Reproducibility of UBM Parameters of Anterior Segment in a Random Subset of Eyes
Supplement 1
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