Abstract
Précis:
Biometric parameters, including binocular difference of anterior chamber depth (ACD), lens vault (LV) in affected eyes, and binocular difference of the LV, had high efficiency in diagnosing acute angle closure (AAC) with zonular laxity.
Purpose:
To investigate the ocular biometric characteristics of eyes with AAC with zonular laxity to further explore the sensitive parameters for preoperative diagnosis.
Methods:
This study included 50 patients with AAC with zonular laxity and 54 patients with AAC without zonular laxity. Demographic data, ocular examination results, and biometric parameters on ultrasound biomicroscopy images were compared between the affected and fellow eyes in 2 groups. Parameters significant in the multiple linear regression model were included in a regression equation and the diagnostic efficiency was evaluated by area under the curve.
Results:
In patients with AAC with zonular laxity, the binocular difference of central ACD, LV in affected eyes, and binocular difference of the LV were significantly larger than those in patients without zonular laxity respectively and these three parameters were all significant in multiple linear regression analysis (all P<0.001). The area under the curve of binocular difference of ACD, LV in affected eyes, and binocular difference of LV were 0.972, 0.796, and 0.855, respectively, with the cutoff values of 0.23, 1.28, and 0.19 mm. The regression equation containing these three parameters was: ln (P/(1−P))=−4.322 + 1.222 [LV in affected eyes (mm)] + 3.657 [binocular difference of LV (mm)] + 6.542 [binocular difference of ACD (mm)], with the accuracy of prediction reaching 94.05%.
Conclusion:
Binocular difference of ACD, LV in affected eyes, and binocular difference of LV had high efficiency in diagnosing AAC with zonular laxity.
Key Words: acute angle closure, zonular laxity, biometric characteristics, diagnosis
Acute angle closure (AAC) is an ophthalmologic emergency that can lead to vision loss in a very short time.1 A challenge in treating AAC is to differentiate between patients with AAC with and without zonular laxity,2 because AAC with zonular laxity could have similar symptoms and clinical features to AAC without zonular laxity.3 Previous research4,5 has proved that zonular laxity is best assessed in phacoemulsification, finding the movement of the entire capsular bag during propagation of the capsular flap and anterior capsule striae during continuous curvilinear capsulorhexis. These signs could reflect the instability of the zonule, and if zonular dehiscence is not observed after full dilation of the pupil intraoperatively, zonular laxity could be diagnosed.6,7 However, there are no specific diagnostic criteria for determining zonular laxity in eyes with AAC before surgery.
In AAC cases with zonular laxity, the occurrence rate of complications during cataract surgery increases, with a risk of posterior capsule rupture, nucleus drop, intraocular lens (IOL) dislocation, and so on.8 If trabeculectomy is operated on patients with AAC with zonular laxity, severe complications like malignant glaucoma may occur postoperatively.9 It is crucial to properly ascertain the condition of the zonule preoperatively because this is a determining factor pertaining to whether the surgery can be safely conducted.
Although there are studies revealing the pathogenesis of acute primary angle closure (APAC) and AAC owing to zonular dehiscence,10–14 the pathogenesis and ocular characteristics of AAC with zonular laxity have not been reported yet. Kwon and Sung12 reported that less hyperopic spherical equivalent, longer axial length, shallower anterior chamber depth (ACD), and higher lens vault (LV) increased the likelihood of zonular instability among patients with a history of AAC attack. However, in that research, the ocular characteristics of patients with zonular laxity were not investigated separately. Moreover, ocular parameters such as anterior and posterior chamber area, the thickness of the lens, and the parameters of ciliary body and choroid have not been investigated yet, and the prediction of zonular laxity preoperatively remains baseless. In this study, we compared the ocular biometric parameters in patients with AAC with and without zonular laxity, to clarify the ocular characteristics of patients with AAC with zonular laxity, reveal the pathogenesis, and set up preoperative diagnostic criteria for AAC with zonular laxity. That would provide a theoretical basis for the selection of treatment schemes and reduce the risk of complications during cataract surgery.
METHODS
Participants
From July 1, 2018 to April 1, 2021, 104 consecutive patients were enrolled who were diagnosed with AAC attack in 1 eye and underwent phacoemulsification and IOL implantation at the Department of Glaucoma, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. The study protocol was approved by the Institutional Review Board and all procedures conformed to the tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants in the study. The age, sex, and affected eye of each subject were recorded. All participants underwent complete ophthalmic evaluation, such as best-corrected visual acuity measurement before surgery, slit-lamp examination, gonioscopy examination, and stereoscopic optic disc examination with a 90-D lens. Axial length (AL) and lens thickness (LT) were measured by IOL Master 500 (Carl Zeiss Meditec), with choroidal thickness measured by optical coherence tomography (RTVue OCT, Optovue Inc.) and corneal endothelium cell counting measured by keratoendoscope (EM-3000, Tomey). IOP was measured during AAC attack (peak IOP) by Goldmann applanation tonometry. Visual field examination was performed with the Humphrey perimetry [Swedish Interactive Threshold Algorithm (SITA) Standard 30-2 or 24-2] if the best-corrected visual acuity was better than 20/400.
The criteria for AAC attack were as follows15: (1) the presence of any two of the following symptoms: ocular pain, nausea or vomiting, and an antecedent history of intermittent blurring of vision with haloes; (2) peak IOP >40 mm Hg; (3) the presence of conjunctival injection, shallow anterior chamber, and mid-dilated fixed pupil with or without corneal epithelial edema; (4) the presence of an occluded angle in the affected eye as determined by gonioscopy. Only subjects with an AAC attack in 1 eye for the first time were included. All the subjects underwent phacoemulsification and IOL implantation by the same ophthalmologist (J.H.) for the treatment of AAC. According to previous studies,4–7 eyes with the movement of the entire capsular bag during propagation of the capsular flap and anterior capsule striae during continuous curvilinear capsulorhexis intraoperatively and without zonular dehiscence were diagnosed as AAC with zonular laxity. The video of the surgery was reviewed by another experienced ophthalmologist at the Department of Cataract in Zhongshan Ophthalmic Center who determined whether the subjects met the diagnostic criteria for zonular laxity. If a discrepancy existed between the two ophthalmologists, subjects would not be diagnosed as AAC with zonular laxity and would be excluded from the current research. Subjects with shallow anterior chamber and narrow angle in both eyes but without signs of zonular laxity were diagnosed as AAC without zonular laxity.
Exclusion criteria were: (1) history of AAC attack or primary angle closure glaucoma in either eye; (2) lens subluxation due to zonular dehiscence detected preoperatively by ultrasound biomicroscopy (UBM) scan or during surgery (lens subluxation due to zonular dehiscence was defined as the invisibility of zonule in some quadrants by UBM, or rupture of the zonule and the displacement of lens equator in some quadrants in the operative setting)16; (3) history of ocular surgeries, including peripheral iridotomy or iridoplasty, or trauma; (4) AAC owing to other ocular diseases such as pseudoexfoliation syndrome, retinitis pigmentosa, Marfan syndrome, homocystinuria, Weill-Marchesani syndrome, and so on; (5) inability to tolerate UBM examination.
UBM
UBM (model SW-3200L; Tianjin Suowei Electronic Technology Co., Ltd.) examination and measurement were performed within 1 week of AAC diagnosis by an experienced physician (H.C.) who was masked to the clinical data. Subjects were examined in a dimly lit room (illumination: 60–70 lux, model TES-1339; TES Electrical Electronic Corp.). Radial scan images at the 12, 3, 6, and 9 o’clock positions centered over the limbus and perpendicular sulcus-to-sulcus scan over the pupillary center were obtained. When performing scans, up to 100 images could be stored as cache in the machine at a speed of 5 images/second. After image capture, the best image was selected by 2 experienced physicians (L.C. and H.C.) who were both masked to the clinical data. The scan had to be centered on the pupil or over the limbus, be well-circumscribed, and show corneal epithelium/endothelium, anterior lens capsule, and iris pigment epithelium. The details of the UBM instruments and steps of examination were similar to those in our previous study.17
Using the special caliper in the instrument, UBM parameters were measured as described previously.18–21 The following parameters of 5 criteria were measured (Fig. 1): (1) parameters of the anterior and posterior chamber (Figs. 1A, B): central ACD, anterior chamber width, anterior chamber area (ACA), posterior chamber area; (2) parameters of anterior chamber angle (Fig. 1C): angle opening distance 500 μm (AOD500), anterior chamber angle 500 μm (ACA500); (3) LV (Fig. 1A); (4) parameters of iris: pupil diameter, iris thickness (IT500, IT750, and IT1000), iris curvature (IC); (5) parameters of ciliary body (Fig. 1E and Fig. 2): trabecular meshwork-ciliary process distance, iris-ciliary process distance (ICPD), trabecular-ciliary process angle (TCPA), anterior placement of ciliary body, maximum ciliary body thickness, ciliary body thickness at the point of the scleral spur, and at the distance of 1000 μm from the scleral spur. Each parameter was measured three times, with the mean values recorded. The parameters of lens position should be used in the study, which can be obtained indirectly through the above data calculation: lens-axial length factor=LT/AL × 10; relative lens position (RLP)=(ACD + 1/2LT)/AL × 10.15 The reliabilities of UBM measurements have been reported in detail in our previous study and elsewhere.21,22
FIGURE 1.
Determinations of parameters on ultrasound biomicroscopy. A, Central ACD is defined as the axial distance from the corneal endothelium to the anterior lens surface. ACW is defined as the distance between the two scleral spurs. PD is defined as the distance between the pupil edges of the iris. LV is defined as the perpendicular distance between the anterior pole of the crystalline lens and the horizontal line joining the two scleral spurs. The dotted line indicates the measurement of the ACA, defined as the cross-sectional area of the anterior chamber bordered by the corneal endothelium, angle, iris surface, and the anterior lens epithelium. B, The dotted line indicates the measurement of the PCA, defined as the cross-sectional area of the posterior chamber bordered by the posterior iris surface, lens zonules, and the anterior border of the lens. C, AOD500 is defined as the perpendicular distance from the point anterior to the scleral spur to the anterior iris surface measured at 500 μm from the scleral spur. ACA500 is defined as the angle formed from the angle recess to points 500 μm from the scleral spur on trabecular meshwork and perpendicular on the surface of the iris. D, Iris thickness is defined as the perpendicular distance from iris pigment epithelium to the anterior iris surface measured at 500, 750, and 1000 μm from the iris root (IT500, IT750, and IT1000, respectively). IC is defined as the maximum perpendicular distance between the iris pigment epithelium and the line connecting the most peripheral to the most central point of the epithelium. E, TCPD is measured as a line extending from a point 500 μm anterior to the scleral spur along the corneal endothelium and dropped perpendicularly through the iris to the most anterior ciliary process. ICPD is measured from the iris pigment epithelium to the ciliary process along the same line as TCPD. ACA indicates anterior chamber area; ACA500, anterior chamber angle 500 μm; ACD, anterior chamber depth; ACW, anterior chamber width; AOD500, angle opening distance 500 μm; IC, iris curvature; ICPD, iris-ciliary process distance; IT500, IT750, IT1000, iris thickness at 500, 750, and 1000 μm from the iris root; LV, lens vault; PCA, posterior chamber area; PD, pupil diameter; TCPD, trabecular meshwork-ciliary process distance.
FIGURE 2.
Determination of ciliary body parameters on ultrasound biomicroscopy. CBTmax is defined as the distance from the innermost point of the ciliary body to the inner wall of the sclera or its extended line. Ciliary body thickness was also measured at the point of the scleral spur (CBT0) and at the distance of 1000 μm (CBT1000) from the scleral spur. APCB is the distance from the most anterior point of the ciliary body to the vertical line from the inner wall of the sclera through the scleral spur. TCPA is the angle between the posterior corneal surface and the anterior surface of the ciliary body. APCB indicates anterior placement of ciliary body; CBT0, ciliary body thickness at the point of the scleral spur; CBTmax, maximum ciliary body thickness; TCPA, trabecular–ciliary process angle.
Statistical Analysis
Statistical analyses were performed using SPSS software version 25.0 (SPSS, Inc.). The means and standard deviations of the above parameters were calculated. Paired t tests were used to detect the differences between the affected eyes with AAC and their fellow eyes. Independent t tests were used to detect the differences in affected eyes between patients with AAC with and without zonular laxity, and the differences in fellow eyes between the two groups. Sex and the affected eye between the two groups were compared using the χ2 test. Univariate regression was conducted to evaluate age, sex, peak IOP, AL, anterior segment parameters, and the binocular difference in each group as predictors of the diagnosis of AAC with zonular laxity. Parameters that were significant at a level of P<0.05 were included in a multiple linear regression model and the regression equation was calculated. The area under the curve (AUC) was used to evaluate the diagnostic efficiency of the parameters that were significant in multiple linear regression analysis, as well as the efficiency of the regression equation. A P<0.05 was considered statistically significant.
RESULTS
A total of 50 patients with AAC with zonular laxity and 54 patients with AAC without zonular laxity met the inclusion criteria and were included in the current study. Demographic and biometric characteristics are summarized in Table 1. AL was shorter in both affected eyes (P=0.006) and fellow eyes (P=0.005) respectively in patients with AAC without zonular laxity compared with patients with zonular laxity. There was no significant difference in demographic characteristics, vision indexes, peak IOP, choroidal thickness, and corneal endothelial cell counting between the two groups (all P>0.05).
TABLE 1.
Demographic and Biometric Characteristics of Patients With AAC With and Without Zonular Laxity
| AAC without zonular laxity, n=54 | AAC with zonular laxity, n=50 | P | ||||||
|---|---|---|---|---|---|---|---|---|
| Affected eyes (A) | Fellow eyes (B) | Affected eyes (C) | Fellow eyes (D) | AvsB* | CvsD* | AvsC† | BvsD† | |
| Sex, male/female | 9/45 | 16/34 | 0.059‡ | |||||
| Age, y | 63.24±8.30 | 62.80±7.42 | 0.776† | |||||
| Affected eye, OD/OS | 34/20 | 24/26 | 0.102‡ | |||||
| Preoperative logMAR BCVA | 0.51±0.28 | 0.20±0.09 | 0.45±0.31 | 0.15±0.06 | <0.001 | <0.001 | 0.468 | 0.047 |
| Peak IOP, mm Hg | 47.55±10.00 | — | 45.03±9.57 | — | — | — | 0.464 | — |
| MD of VF, dB | −10.34±8.31 | −5.89±5.19 | −8.30±8.88 | −3.26±2.42 | <0.001 | 0.001 | 0.090 | 0.006 |
| PSD of VF, dB | 4.40±2.57 | 3.72±2.29 | 3.69±2.58 | 2.74±2.05 | 0.165 | 0.017 | 0.096 | 0.01 |
| VFI, % | 77.25±28.71 | 90.39±15.13 | 83.36±28.12 | 96.46±4.98 | 0.001 | <0.001 | 0.047 | 0.017 |
| Axial length, mm | 22.25±0.78 | 22.27±0.70 | 22.69±0.67 | 22.72±0.71 | 0.891 | 0.353 | 0.006 | 0.005 |
| Choroidal thickness, μm | 325.63±96.22 | 315.04±102.06 | 311.17±103.64 | 313.38±109.69 | 0.696 | 0.554 | 0.853 | 0.561 |
| Corneal endothelial cell counting, n/mm2 | 2189.92±840.64 | 2594.00±391.72 | 2467.30±490.47 | 2616.84±359.20 | 0.011 | 0.455 | 0.230 | 0.915 |
Data are presented as mean ± SD. Bold values indicate statistical significance.
Paired t test.
Independent t test.
χ2 test.
AAC indicates acute angle closure; BCVA, best-corrected visual acuity; IOP, intraocular pressure; MD, mean deviation; OD, right eye; OS, left eye; PSD, pattern standard deviation; VF, visual field; VFI, visual field index; vs, compared with.
Comparison of parameters of the anterior and posterior chamber is shown in Table 2 and Figure 3. ACD, ACA, AOD500, and ACA500 were smaller in affected eyes than in fellow eyes in both groups (all P<0.001). In affected eyes, they were even smaller in patients with AAC with zonular laxity than in those without zonular laxity (P<0.001, <0.001, 0.020, 0.025, respectively), while in fellow eyes they were larger in patients with AAC with zonular laxity (P<0.001, 0.006, <0.001, <0.001, respectively).
TABLE 2.
Comparison of Parameters of Anterior and Posterior Chamber of Patients With AAC With and Without Zonular Laxity
| AAC without zonular laxity | AAC with zonular laxity | P | ||||||
|---|---|---|---|---|---|---|---|---|
| Affected eyes (A) | Fellow eyes (B) | Affected eyes (C) | Fellow eyes (D) | AvsB* | CvsD* | AvsC† | BvsD† | |
| ACD, mm | 1.73±0.22 | 1.82±0.22 | 1.49±0.24 | 2.03±0.32 | <0.001 | <0.001 | <0.001 | <0.001 |
| ACW, mm | 11.19±1.87 | 11.23±0.56 | 11.57±0.72 | 11.36±0.82 | 0.008 | 0.002 | 0.148 | 0.173 |
| ACA, mm2 | 12.15±1.73 | 12.79±1.80 | 11.20±1.39 | 13.67±1.21 | <0.001 | <0.001 | <0.001 | 0.006 |
| PCA, mm2 | 1.20±0.35 | 1.05±0.44 | 1.13±0.23 | 1.07±0.36 | 0.341 | 0.254 | 0.582 | 0.427 |
| AOD500, mm | 0.024±0.041 | 0.072±0.052 | 0.019±0.073 | 0.134±0.077 | <0.001 | <0.001 | 0.020 | <0.001 |
| ACA500, deg | 2.342±3.901 | 8.302±6.211 | 1.262±4.023 | 14.282±6.811 | <0.001 | <0.001 | 0.025 | <0.001 |
Data are presented as mean±SD. Bold values indicate statistical significance.
Paired t test.
Independent t test.
AAC indicates acute angle closure; ACA, anterior chamber area; ACA500, anterior chamber angle 500 μm; ACD, central anterior chamber depth; ACW, anterior chamber width; AOD500, angle opening distance 500 μm; PCA, posterior chamber area; vs, compared with.
FIGURE 3.
Comparison of parameters between patients with AAC with and without zonular laxity. A, ACD; B, ACA; C, AOD500; and D, ACA500 were smaller in affected eyes than in fellow eyes in both groups. In affected eyes, they were even smaller in patients with AAC with zonular laxity than in patients without zonular laxity, while in fellow eyes were larger in patients with AAC with zonular laxity. E, LV was larger in affected eyes than in fellow eyes in both groups and larger in affected eyes in patients with AAC with zonular laxity. F, RLP was smaller in affected eyes in patients with zonular laxity than in those without zonular laxity. G, IT500; H, IT750; and I, IT1000 were smaller in affected eyes in patients with AAC with zonular laxity than in their fellow eyes and affected eyes in patients without zonular laxity. J, IC was smaller in affected eyes than in fellow eyes, but it is larger in affected eyes in patients with AAC with zonular laxity. K, TCPA was smaller in affected eyes in patients with AAC without zonular laxity than in their fellow eyes and affected eyes in patients with AAC with zonular laxity. L, CBT0 was significantly thinner in affected eyes than in fellow eyes in patients with AAC without zonular laxity. *P<0.05, **P<0.01, ***P<0.001. Error bars: standard deviation. AAC indicates acute angle closure; ACA, anterior chamber area; ACA500, anterior chamber angle 500 μm; ACD, central anterior chamber depth; AOD500, angle opening distance 500 μm; CBT0, ciliary body thickness at the point of the scleral spur; IC, iris curvature; IT500, IT750, IT1000, iris thickness at 500, 750, and 1000 μm from the iris root; LV, lens vault; RLP, relative lens position; TCPA, trabecular–ciliary process angle.
Comparison of parameters of lens, iris, and ciliary body is shown in Table 3 and Figure 3. There was no significant difference in LT and lens-axial length factor in affected eyes between the two groups (P>0.05). LV was larger in affected eyes than in fellow eyes in both groups (both P<0.05), and it was larger in affected eyes in patients with AAC with zonular laxity than in those without zonular laxity (P<0.001). In affected eyes, RLP was smaller in patients with zonular laxity than in those without zonular laxity (P<0.001). As shown in Table 3, IT500, IT750, and IT1000 were smaller in affected eyes than fellow eyes in patients with AAC with zonular laxity (all P<0.001) and affected eyes in patients without zonular laxity (all P<0.001). IC was larger in affected eyes in patients with zonular laxity than in patients without zonular laxity (P=0.006). As for parameters of the ciliary body, ICPD was smaller in affected eyes in patients without zonular laxity than in patients with zonular laxity (P=0.003). TCPA was smaller in affected eyes in patients without zonular laxity than their fellow eyes and affected eyes in patients with zonular laxity (P=0.007, 0.005, respectively).
TABLE 3.
Comparison of Parameters of Lens, Iris, and Ciliary Body of Patients With AAC With and Without Zonular Laxity
| AAC without zonular laxity | AAC with zonular laxity | P | ||||||
|---|---|---|---|---|---|---|---|---|
| Affected eyes (A) | Fellow eyes (B) | Affected eyes (C) | Fellow eyes (D) | AvsB* | CvsD* | AvsC† | BvsD† | |
| LT, mm | 5.042±0.250 | 5.064±0.231 | 5.113±0.424 | 5.042±0.401 | 0.329 | 0.007 | 0.409 | 0.912 |
| LV, mm | 1.089±0.241 | 0.997±0.228 | 1.444±0.357 | 0.979±0.267 | 0.003 | <0.001 | <0.001 | 0.507 |
| RLP | 1.928±0.097 | 1.946±0.116 | 1.779±0.163 | 2.026±0.122 | 0.319 | <0.001 | <0.001 | 0.003 |
| LAF | 2.299±0.193 | 2.263±0.181 | 2.285±0.197 | 2.264±0.192 | 0.218 | 0.273 | 0.800 | 0.963 |
| PD, mm | 4.162±1.082 | 2.869±0.771 | 3.957±1.144 | 2.950±1.050 | <0.001 | <0.001 | 0.382 | 0.641 |
| IT500, mm | 0.374±0.089 | 0.383±0.091 | 0.317±0.081 | 0.387±0.074 | 0.353 | <0.001 | <0.001 | 0.739 |
| IT750, mm | 0.403±0.080 | 0.392±0.099 | 0.336±0.074 | 0.396±0.075 | 0.617 | <0.001 | <0.001 | 0.799 |
| IT1000, mm | 0.449±0.081 | 0.421±0.108 | 0.368±0.078 | 0.416±0.084 | 0.346 | <0.001 | <0.001 | 0.993 |
| IC, mm | 0.126±0.104 | 0.246±0.091 | 0.185±0.103 | 0.242±0.088 | <0.001 | 0.01 | 0.006 | 0.815 |
| TCPD, mm | 0.487±0.143 | 0.556±0.163 | 0.540±0.189 | 0.579±0.133 | 0.024 | 0.124 | 0.157 | 0.200 |
| ICPD, mm | 0.122±0.135 | 0.097±0.126 | 0.199±0.154 | 0.092±0.116 | 0.207 | <0.001 | 0.003 | 0.720 |
| TCPA, deg | 50.779±13.134 | 57.173±15.463 | 59.148±14.324 | 59.353±9.921 | 0.007 | 0.651 | 0.005 | 0.293 |
| APCB, mm | 0.545±0.217 | 0.599±0.226 | 0.482±0.197 | 0.579±0.200 | 0.024 | 0.124 | 0.157 | 0.200 |
| CBT0, mm | 0.930±0.201 | 1.004±0.201 | 1.003±0.188 | 1.024±0.140 | 0.039 | 0.204 | 0.144 | 0.506 |
| CBT1000, mm | 0.716±0.174 | 0.722±0.154 | 0.747±0.164 | 0.762±0.150 | 0.776 | 0.308 | 0.309 | 0.178 |
| CBTmax, mm | 1.005±0.219 | 1.083±0.141 | 1.018±0.209 | 1.120±0.177 | 0.057 | 0.010 | 0.625 | 0.157 |
Data are presented as mean ± SD. Bold values indicate statistical significance.
Paired t test.
Independent t test.
AAC indicates acute angle closure; APCB, anterior placement of ciliary body; CBT0, ciliary body thickness at the point of the scleral spur; CBT1000, ciliary body thickness at the distance of 1000 μm from the scleral spur; CBTmax, ciliary body thickness; IC, iris curvature; ICPD, iris-ciliary process distance; IT500, IT750, IT1000, iris thickness at 500, 750, and 1000 μm from the iris root; LAF, lens-axial length factor; LT, lens thickness; LV, lens vault; PD, pupil diameter; RLP, relative lens position; TCPA, trabecular–ciliary process angle; TCPD, trabecular meshwork-ciliary process distance; vs, compared with.
We also compared the binocular difference of all the parameters, as shown in Table 4 and Figure 4. Binocular difference of ACD, ACA, AOD500, ACA500, LT, LV, RLP, IT500, IT750, and IT1000 was larger in patients with zonular laxity respectively, while the binocular difference of IC was smaller (all P<0.05).
TABLE 4.
Comparison of the Binocular Difference of the Parameters of Patients With AAC With and Without Zonular Laxity
| Binocular difference | |||
|---|---|---|---|
| AAC without zonular laxity | AAC with zonular laxity | P * | |
| ACD, mm | −0.091±0.108 | −0.542±0.344 | <0.001 |
| ACW, mm | −0.094±1.881 | 0.170±0.403 | 0.776 |
| ACA, mm2 | −0.643±0.204 | −0.882±0.330 | <0.001 |
| PCA, mm2 | −0.150±0.029 | −0.021±0.024 | 0.745 |
| AOD500, mm | −0.052±0.076 | −0.104±0.077 | 0.007 |
| ACA500, degrees | −7.109±7.215 | −11.890±7.724 | 0.012 |
| LT, mm | −0.017±0.111 | 0.074±0.188 | 0.002 |
| LV, mm | 0.082±0.165 | 0.466±0.230 | <0.001 |
| RLP | −0.018±0.118 | −0.247±0.190 | <0.001 |
| LAF | 0.036±0.192 | 0.021±0.117 | 0.684 |
| PD, mm | 1.299±1.035 | 0.979±1.502 | 0.183 |
| IT500, mm | −0.012±0.093 | −0.072±0.088 | 0.004 |
| IT750, mm | 0.010±0.093 | −0.059±0.084 | 0.001 |
| IT1000, mm | 0.027±0.087 | −0.048±0.095 | <0.001 |
| IC, mm | −0.131±0.108 | −0.052±0.130 | 0.005 |
| TCPD, mm | −0.071±0.185 | −0.042±0.201 | 0.517 |
| ICPD, mm | 0.027±0.145 | 0.107±0.182 | 0.061 |
| TCPA, deg | −6.788±15.774 | −0.458±13.201 | 0.068 |
| APCB, mm | −0.054±0.253 | −0.093±0.223 | 0.491 |
| CBT0, mm | −0.071±0.270 | −0.024±0.171 | 0.462 |
| CBT1000, mm | −0.008±0.233 | −0.017±0.152 | 0.857 |
| CBTmax, mm | −0.074±0.248 | −0.106±0.223 | 0.143 |
Data are presented as mean ± SD. Bold values indicate statistical significance.
Independent t-test.
AAC indicates acute angle closure; ACA, anterior chamber area; ACA500, anterior chamber angle 500 μm; ACD, central anterior chamber depth; ACW, anterior chamber width; AOD500, angle opening distance 500 μm; APCB, anterior placement of ciliary body; CBT0, ciliary body thickness at the point of the scleral spur; CBT1000, ciliary body thickness at the distance of 1000 μm from the scleral spur; CBTmax, ciliary body thickness; IC, iris curvature; ICPD, iris-ciliary process distance; IT500, IT750, IT1000, iris thickness at 500, 750, and 1000 μm from the iris root; LAF, lens-axial length factor; LT, lens thickness; LV, lens vault; PCA, posterior chamber area; PD, pupil diameter; RLP, relative lens position; TCPA, trabecular–ciliary process angle; TCPD, trabecular meshwork-ciliary process distance.
FIGURE 4.
Comparison of the binocular difference of the parameters between patients with AAC with and without zonular laxity. A-J, binocular difference values of ACD, ACA, AOD500, ACA500, LT, LV, RLP, IT500, IT750, and IT1000 were all larger in patients with AAC with zonular laxity than in those without zonular laxity respectively. K, binocular difference of IC was smaller in patients with zonular laxity. *P<0.05, **P<0.01, ***P<0.001. Error bars: standard deviation. AAC indicates acute angle closure; ACA, anterior chamber area; ACA500, anterior chamber angle 500 μm; ACD, central anterior chamber depth; AOD500, angle opening distance 500 μm; IC, iris curvature; IT500, IT750, IT1000, iris thickness at 500, 750, and 1000 μm from the iris root; LT, lens thickness; LV, lens vault; RLP, relative lens position.
The results of regression analysis are shown in Table 5. The diagnosis of AAC with zonular laxity was significantly associated with ACD, LV in affected eyes and binocular difference of ACD and LV (P=0.003, <0.001, <0.001, <0.001, respectively). Among these parameters, LV in affected eyes and binocular difference of ACD and LV were significant in multiple linear regression analysis. AUC was used to evaluate the diagnostic efficiency of LV in affected eyes and the binocular difference of ACD and LV, counting 0.796, 0.972, and 0.855, respectively (Figs. 5A–C). The cutoff values were 1.28, 0.23, and 0.19, respectively, indicating that when LV in affected eyes exceeds 1.28 mm, or binocular difference of ACD exceeds 0.23 mm, or binocular difference of LV exceeds 0.19 mm, the diagnosis of AAC with zonular laxity should be considered. The regression equation containing these three parameters was:
TABLE 5.
Univariate and Multivariate Regression Analyses of Diagnosis of AAC With Zonular Laxity
| Univariate | Multivariate | |||
|---|---|---|---|---|
| OR (95% CI) | P | OR (95% CI) | P | |
| Age | 0.96 (0.68–1.23) | 0.084 | ||
| Sex | 1.75 (1.22–3.13) | 0.477 | ||
| Peak IOP | 0.96 (0.54–1.50) | 0.375 | ||
| Axial length | 1.22 (0.79–1.55) | 0.156 | ||
| ACD | 0.63 (0.40–1.22) | 0.003 | 0.99 (0.39–1.21) | 0.421 |
| ACA | 1.33 (0.29–2.67) | 0.363 | ||
| AOD500 | 0.95 (0.58–1.35) | 0.321 | ||
| ACA500 | 0.85 (0.13–1.09) | 0.102 | ||
| LT | 1.12 (0.99–1.21) | 0.219 | ||
| LV | 1.89 (0.79–3.42) | <0.001 | 1.45 (1.10–2.46) | 0.029 |
| RLP | 1.95 (1.39–4.22) | 0.292 | ||
| IT500 | 1.07 (0.30–2.17) | 0.095 | ||
| IT750 | 1.35 (1.06–1.88) | 0.292 | ||
| IT1000 | 1.22 (0.37–1.21) | 0.899 | ||
| IC | 0.99 (0.15–2.46) | 0.486 | ||
| TCPD | 1.64 (1.17–2.00) | 0.358 | ||
| TCPA | 1.08 (0.05–3.01) | 0.867 | ||
| Binocular difference of ACD | 1.68 (0.81–2.22) | <0.001 | 1.89 (1.33–4.47) | 0.004 |
| Binocular difference of AOD500 | 0.99 (0.16–1.30) | 0.307 | ||
| Binocular difference of ACA500 | 0.82 (0.77–0.98) | 0.121 | ||
| Binocular difference of LT | 1.03 (0.70–2.87) | 0.091 | ||
| Binocular difference of LV | 0.56 (0.29–0.83) | <0.001 | 1.38 (1.03–3.95) | 0.047 |
| Binocular difference of IC | 1.03 (0.45–2.07) | 0.176 | ||
Bold values indicate statistical significance.
AAC indicates acute secondary angle closure; ACA, anterior chamber area; ACA500, anterior chamber angle 500 μm; ACD, central anterior chamber depth; AOD500, angle opening distance 500 μm; IC, iris curvature; IOP, intraocular pressure; IT500, IT750, IT1000, iris thickness at 500, 750, and 1000 μm from the iris root; LT, lens thickness; LV, lens vault; OR, odds ratio; RLP, relative lens position; TCPA, trabecular–ciliary process angle; TCPD, trabecular meshwork-ciliary process distance.
FIGURE 5.
ROC curves. A, Binocular difference of ACD; B, binocular difference of LV; C, LV in affected eyes (AUC=0.972, 0.855, 0.796, respectively) showed a high diagnostic ability for differentiating between AAC with and without zonular laxity. D, The regression equation including the three parameters mentioned above showed better diagnostic ability (AUC=0.981) than any of the parameters alone. AAC indicates acute angle closure; ACD, central anterior chamber depth; AUC, area under the curve; LV, lens vault; ROC, receiver operator characteristic.
ln (P/(1 − P)) = −4.322 + 1.222 [LV in affected eyes (mm)] + 3.657 [binocular difference of LV (mm)] + 6.542 [binocular difference of ACD (mm)]
In this equation, P referred to the possibility of diagnosing AAC with zonular laxity. The AUC of the equation was 0.981 as shown in Figure 5D and the accuracy of prediction of the regression equation reached 94.05%.
DISCUSSION
In the current study, we compared the ocular biometric parameters between patients with AAC with and without zonular laxity. We found that three parameters, including LV in affected eyes, the binocular difference of ACD, and the binocular difference of LV, had high efficiency in the diagnosis of AAC with zonular laxity. The regression equation containing these parameters had higher diagnostic accuracy reaching 94.05%. To the best of our knowledge, this is the first study investigating the pathogenesis and preoperative diagnostic criteria of AAC with zonular laxity by comparing the ocular biometric parameters in patients with AAC with and without zonular laxity, which provides a piece of moderate-certainty evidence for developing appropriate follow-up treatment of different types of AAC.
ACD has been identified as an important clinical characteristic for distinguishing between APAC and lens-induced AAC.2 Luo et al and Xing et al2,13 found that the anterior chamber was shallower in AAC eyes with lens subluxation due to zonular dehiscence than in APAC eyes (1.34±0.45 mm vs. 1.80±0.24 mm, 1.25±0.35 mm vs. 1.64±0.26 mm, respectively). In the current study, ACD in eyes with zonular laxity (1.49±0.24 mm) was larger than that in eyes with secondary AAC in the 2 studies mentioned above. The inconsistency may arise from the subjects included. The 2 studies mentioned above included eyes with lens subluxation due to zonular dehiscence, leading to a more severe forward movement of the displaced lens. But in eyes with zonular laxity, the weak zonule may still have tension to a certain extent stopping the lens from severe forward movement, which makes it more difficult to differentiate AAC with zonular laxity from that without zonular laxity. Another important characteristic of patients with AAC with zonular laxity was the high asymmetry in ACD between the affected eyes and the fellow eyes. The binocular difference of ACD was 0.542±0.344 mm in AAC cases with zonular laxity, significantly larger than that in patients without zonular laxity, counting 0.091±0.108 mm. Moreover, multiple linear regression analysis showed that the binocular difference of ACD had a high diagnostic ability for diagnosing AAC with zonular laxity, with the AUC reaching 0.972. The cutoff value of the binocular difference of ACD was 0.23 mm, indicating that the diagnosis of AAC with zonular laxity should be considered when the binocular difference of ACD exceeded 0.23 mm in patients with AAC. These results provided a new diagnostic basis for AAC with zonular laxity. Consistent with the results of ACD, the current study also revealed that eyes with zonular laxity had narrower anterior chamber angle and smaller cross-sectional area of the anterior chamber than eyes without zonular laxity, suggesting that a more crowded anterior segment was one of the characteristics of AAC with zonular laxity. This characteristic indicated that pupillary block, as well as the position of the lens, was one of the important mechanisms of AAC with zonular laxity.
As shown in our results, there was no significant difference in LT in affected eyes between patients with AAC with and without zonular laxity in the current study. On the other hand, LV in eyes with zonular laxity was larger than that in eyes without zonular laxity in the current study, which was consistent with the results of Kwon et al.12 LV depended on the location and the thickness of the lens. Since the thickness of the lens was similar in affected eyes between the two groups, larger LV suggested a more forward-moving lens. In addition, RLP was smaller in eyes with zonular laxity, indicating that the lens was positioned more forward when the zonule was loose. This indicated that zonular laxity could lead to the movement of the lens toward the anterior chamber and finally result in the shallow anterior chamber and angle closure, which might be a possible cause of AAC with zonular laxity. Multiple linear regression analysis revealed that LV in affected eyes was another important factor in the diagnosis of AAC with zonular laxity, with AUC reaching 0.796. The cutoff value of LV in affected eyes was 1.28 mm. In other words, when LV in eyes with AAC exceeded 1.28 mm, the diagnosis of AAC with zonular laxity should be considered. We also found that the binocular difference of LV was larger in patients with AAC with zonular laxity. The AUC of the binocular difference of LV reached 0.855, showing high diagnostic efficiency in the diagnosis of AAC with zonular laxity, with the cutoff value counting 0.19 mm.
Our results revealed that three parameters, including binocular difference of ACD, LV in affected eyes, and binocular difference of LV, had a high ability for differentiating between AAC with and without zonular laxity. Moreover, by logistic regression analysis, we figured out a regression equation: ln (P/(1 − P)) = −4.322 + 1.222 [LV in affected eyes (mm)] + 3.657 [binocular difference of LV (mm)] + 6.542 [binocular difference of ACD (mm)]. The AUC of this equation was 0.981 and the prediction accuracy reached 94.05%, meaning that using the equation including these three parameters had a higher diagnostic ability in the diagnosis of AAC with zonular laxity. This could be beneficial to the differentiation of AAC with and without zonular laxity preoperatively and conducive to the choice of treatment methods and the prediction of prognosis.
Our previous study has revealed that thickness, position, shape, and dynamic change of the iris played an important role in the pathogenesis of primary angle closure glaucoma.23 In the current study, peripheral IT was smaller in affected eyes in patients with AAC with zonular laxity than in those without zonular laxity. In AAC eyes with zonular laxity, the iridolenticular diaphragm moves forward and generates pushing force toward the iris. The force combined with the effect of high IOP from the reverse direction makes the loose iris tissue thinner.24 IC was larger in affected eyes in cases with zonular laxity. IC could reflect the extent of iris bowing, which depended on the pressure difference between the posterior and anterior chamber.25 Lens in eyes with zonular laxity moved more forward to the anterior chamber and the contact area between the iris and lens increased, resulting in a rise of resistance for aqueous to flow into the anterior chamber and aggravated pupillary block. This might reveal the pathogenesis of AAC with zonular laxity.
Although there is various equipment for visualizing the anterior segment, UBM has been proven to be one of the most helpful methods for visualizing the posterior chamber structures, including the lens zonule and the ciliary body.26 Therefore, we used UBM for the evaluation of the integrity of zonule as well as the measurement of ciliary body parameters. In the current study, ICPD and TCPA were smaller in affected eyes in patients with AAC without zonular laxity than in those with zonular laxity, indicating that the ciliary body in eyes with zonular laxity was not as anteriorly rotated as those without zonular laxity. Therefore, the ciliary body might not be a major risk factor for AAC with zonular laxity.
There were several limitations in this study. First, this is a cross-sectional study comparing AAC with and without zonular laxity; a longitudinal study is better to further reveal the dynamic pathogenesis of AAC with zonular laxity. UBM and other ocular measurements before the onset of AAC were not available for analysis because of the nature of the study. The biometric values might be affected by a combination of multiple angle closure components, such as pupillary block and the forward moving of the lens. Second, although there was a significant difference in parameters of anterior chamber angle, iris, and ciliary body between patients with AAC with and without zonular laxity, only ACD and LV were included in multiple linear regression analysis and showed high diagnostic efficiency. ACD and LV could also be accurately measured by anterior segment optical coherence tomography (AS-OCT), which did not require contact with the ocular surface and was more maneuverable than UBM. Further study should be conducted to investigate the role of anterior segment optical coherence tomography in differentiating between AAC with and without zonular laxity. Third, the current study only included patients with AAC with zonular laxity in 1 eye, and thus the parameters of binocular difference may not be applied to the diagnosis of patients with AAC in both eyes. However, the biometric characteristics of affected eyes in patients with AAC with zonular laxity have been investigated in the current research and parameters (LV in affected eyes, for instance) could be meaningful in the diagnosis of patients with zonular laxity in both eyes. Fourth, the diagnosis of zonular laxity was based on the signs of capsular bag intraoperatively, which could be subjective. However, the video of the surgery was reviewed by another experienced ophthalmologist to avoid misdiagnosis owing to subjectivity.
In conclusion, binocular difference of ACD, LV in affected eyes with AAC, and binocular difference of LV had high efficiency in differentiating AAC with and without zonular laxity. The regression equation containing these three parameters could increase the accuracy in the preoperative diagnosis of AAC with zonular laxity.
ACKNOWLEDGMENTS
The authors thank Professor Ling Jin for her statistical help.
Footnotes
H.C. and L.Y. contributed equally to this work.
This work was supported by the National Natural Science Foundation of China (82271081), the Natural Science Foundation of Guangdong Province in China (2021A1515012142, 2022A1515010302), and the Research Grant from Guangzhou Municipal Science and Technology Bureau in China (202201020268).
Disclosure: The authors declare no conflict of interest.
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