December 2013
Volume 54, Issue 13
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Glaucoma  |   December 2013
Choroidal Thickness in the Subtypes of Angle Closure: An EDI-OCT Study
Author Affiliations & Notes
  • Wenbin Huang
    Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, China
  • Wei Wang
    Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, China
  • Xinbo Gao
    Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, China
  • Xingyi Li
    Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, China
  • Zheng Li
    Department of Ophthalmology, The Affiliated 1st People's Hospital of Chenzhou City, Nanhua University, Chenzhou, China
  • Minwen Zhou
    Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, China
  • Shida Chen
    Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, China
  • Xiulan Zhang
    Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, China
  • Correspondence: Xiulan Zhang, Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-sen University, 54 S. Xianlie Road, Guangzhou, China 510060; zhangxl2@mail.sysu.edu.cn
Investigative Ophthalmology & Visual Science December 2013, Vol.54, 7849-7853. doi:https://doi.org/10.1167/iovs.13-13158
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      Wenbin Huang, Wei Wang, Xinbo Gao, Xingyi Li, Zheng Li, Minwen Zhou, Shida Chen, Xiulan Zhang; Choroidal Thickness in the Subtypes of Angle Closure: An EDI-OCT Study. Invest. Ophthalmol. Vis. Sci. 2013;54(13):7849-7853. https://doi.org/10.1167/iovs.13-13158.

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

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Abstract

Purpose.: To evaluate choroidal thickness (CT) in the subtypes of angle-closure (AC) disease compared with CT in a healthy control.

Methods.: A total of 297 subjects (eyes) were enrolled in the study: 87 were nonglaucoma controls and 210 were AC subtype eyes (primary AC suspect [PACS], 73 eyes; acute primary AC [APAC], 46 eyes; primary AC [PAC], 35 eyes; and primary AC glaucoma [PACG], 56 eyes). Enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT) was used to measure the macular CT in the subtypes of AC disease and in healthy control subjects. The average CT was compared among the five groups.

Results.: Thinner CT was associated with older age and longer axial length (AL) (all P < 0.001). All AC groups had thicker subfoveal CT (SFCT) compared with the control eyes (all P < 0.05), even after controlling for age and the AL factor. Acute primary angle-closure eyes had the thickest SFCT and were 61.9-μm thicker than healthy eyes, while PACS, PAC, and PACG eyes were 32.9-, 30.9-, and 25.4-μm thicker than healthy eyes, respectively. No significant difference was observed among the PACS, PAC, and PACG groups.

Conclusions.: Increased CT might be another anatomic characteristic of AC eyes. These findings may support the hypotheses that choroidal expansion is a contributing factor to the development of AC disease.

Introduction
In Asian populations, nearly as many cases of glaucoma may be due to primary angle-closure glaucoma (PACG) as are due to open-angle glaucoma. 1,2 Chinese populations are reported to represent one of highest rates of PACG. In China, PACG is estimated to cause unilateral blindness in 1.5 million individuals and bilateral blindness in another 1.5 million. 2  
Angle-closure (AC) disease is an anatomic disorder characterized by biometric factors such as shallow anterior chamber depth (ACD), thick crystalline lens, short axial length (AL), and steep corneal curvature associated with angle closure. 35 Pupillary-block and angle-crowding mechanisms of filtration angle closure have been proposed as the two main mechanisms underlying the pathogenesis of AC disease. 6,7 However, according to Quigley et al., 7 choroidal expansion may also play an important role in this disease. 
Our previous studies using enhanced depth imaging optical coherence tomography (EDI-OCT) indicated that a higher level of macular CT occurs in acute primary AC (APAC) eyes than in primary AC suspect (PACS) eyes, and that CT was thicker in APAC and PACS eyes than in healthy control eyes. 8,9 Given the evidence from our previous studies, we hypothesize that CT, to some degree, takes part in the pathogenesis of AC disease. However, the trends in CT distribution and variation during progression of AC disease remain unclear. In the present study, we measured the CT in the subtypes of AC disease (including PACS, APAC, primary AC [PAC], and PACG) to further research the role of CT in AC disease. 
Methods
Subject Recruitment
All participants in this study received a detailed explanation about the study and signed an informed consent form in accordance with the principles embodied in the Declaration of Helsinki. This study was approved by the ethical review committee of Zhongshan Ophthalmic Center. Participants were recruited prospectively and consecutively for this study between July 2012 and July 2013. 
Participants were selected as a convenience sample of patients and those accompanying them at the Glaucoma Department, Zhongshan Ophthalmic Center. One eye of each subject was included. Subjects were older than 18 years, had clear ocular media, and had no evidence of glaucoma or were diagnosed as PACS, APAC, PAC, and PACG. None of the patients had ever received any antiglaucomatous surgical treatment before the EDI-OCT measurement. The definitions of each subgroup in the study were as follows 10,11
  1.  
    Primary angle-closure suspects: PACS was defined as a pigmented trabecular meshwork in the eye not visible for greater than or equal to 180° under static gonioscopy (Goldmann) and IOP lower than 21 mm Hg, without peripheral anterior synechiae (PAS) or glaucomatous neuropathy;
  2.  
    Acute primary angle closure 11 : Presence of at least two of the following symptoms to ocular or periocular pain, nausea and/or vomiting, and an antecedent history of intermittent blurring of vision with halos; presenting IOP of at least 22 mm Hg, and the presence of at least three of the following signs to conjunctival injection, corneal epithelial edema, middilated unreactive pupil, and a shallow anterior chamber; and the presence of an occluded angle in the affected eye, verified by gonioscopy;
  3.  
    Primary angle closure: These were eyes with narrow angles (defined as eyes in which the posterior trabecular meshwork was not seen for at least 180° on indentation gonioscopy in the primary position), with PAS and/or raised IOP (defined as an IOP > 21 mm Hg), but without glaucomatous optic neuropathy or visual field loss. Peripheral anterior synechiae were defined as abnormal adhesions of the iris to the angle that were present at the level of the anterior trabecular meshwork or higher. They were deemed to be present if apposition between the peripheral iris and angle structures could not be broken, despite indentation gonioscopy; and
  4.  
    Primary angle-closure glaucoma: These were eyes with PAC and glaucomatous optic neuropathy (defined as a vertical cup/disc (C/D) ratio > 0.7 and/or C/D asymmetry > 0.2 and/or focal notching), with compatible visual field loss on static automated perimetry (SITA standard algorithm with a 24-2 test pattern; Humphrey Visual Field Analyser II; Carl Zeiss Meditec, Dublin, CA). This was defined as a glaucoma hemifield test outside normal limits, with an abnormal pattern and a SD of P less than 5% in the healthy population and fulfilling test reliability criteria (fixation losses < 20%, false positives < 33%, and/or false negatives ≤ 33%).
All the eyes underwent an ultrasound biomicroscopy (UBM) and gonioscopy examination to confirm the existence of a narrow-angle component. Acute primary angle-closure eyes were enrolled when the IOP was decreased and when the optical media had cleared following treatment with adjunctive glaucoma medications or anterior chamber paracentesis. All APAC eyes were scheduled for peripheral iridectomy, iridoplasty, or trabeculectomy and their fellow PACS eyes scheduled for prophylactic peripheral iridectomy. Other PACS and PAC eyes were scheduled for prophylactic peripheral iridectomy. All the EDI-OCT measurements were performed before these procedures. 
The medication treatment for APAC and PACG was standardized as follows: topical beta-blocker (timolol 0.5%) twice daily and/or brinzolamide (Azopt; Alcon Laboratories, Elkridge, MD), and/or topical alpha-2 agonists (Alphagan; Allergan, Inc., Irvine, CA). For APAC, topical pilocarpine 1%, four times daily, and topical steroids were also added. Other treatments included oral acetazolamide 250 mg, three times daily, and intravenous mannitol 20% at 1 to 2 g/kg, 4 hours after the initiation of the treatment in cases where the IOP was not reduced by 20% from the initial IOP, unless contraindicated by systemic disease (e.g., congestive heart failure). 
Normals were included who had no prior history of eye disease other than cataract, no intraocular surgery, no glaucomatous optic neuropathy, and no history of IOP exceeding 21 mm Hg. 
Exclusion criteria for participants enrolled in this study included: a secondary acute attack because of lens subluxation, uveitis, iris neovascularization, trauma, tumor, or any obvious cataract leading to an intumescent lens; diabetes or systemic hypertension; a history of intraocular surgery; inability to tolerate gonioscopy or UBM examination; high myopia or hyperopia with a spherical equivalent (SE) refractive error (greater than 3 or −3 diopters [D]); any retinal or neuro-ophthalmologic disease; and clinically relevant opacities of the optical media and low-quality images due to unstable fixation or severe cataract. 
Examination
All eyes of the subjects underwent a thorough ophthalmic evaluation, including slit-lamp biomicroscopy, IOP measurement (applanation tonometry), gonioscopy, fundus examination, UBM, and B-scanning. They also underwent refractive error examination using an autorefractometer (KR-8900, version 1.07; Topcon Corporation, Tokyo, Japan) and AL measurements using partial optical coherence interferometry (IOL-Master; Carl Zeiss Meditec, La Jolla, CA). The central anterior chamber depth (ACD), defined as the distance from the anterior corneal surface to the anterior crystalline lens surface; the lens thickness (LT), defined as the distance from the anterior to the posterior lens surface; and the vitreous chamber depth (VCD), defined as the distance from the posterior lens surface to the inner limiting membrane, were measured by A-mode ultrasonography (CINESCAN; Quantel Medical, Clermont-Ferrand, France). The median was used for the analysis of all repeat measurements. Demographic data were collected, such as age, sex, and blood pressure at imaging. Diastolic blood pressure (DBP), systolic blood pressure (SBP), mean blood pressure (MBP), diastolic ocular perfusion pressure (DOPP), systolic ocular perfusion pressure (SOPP), and mean ocular perfusion pressure (MOPP) were collected for each subject. Mean blood pressure, DOPP, SOPP, and MOPP were calculated according to the following formulas 12 : MBP = DBP + 1/3(SBP − DBP); DOPP = DBP − IOP; SOPP = SBP − IOP; and MOPP = MBP − IOP. 
EDI-OCT Examination
A single experienced ophthalmologist, blinded to the clinical diagnosis of the patients, performed the EDI-OCT examinations in the morning, always around 10 AM. 
All subjects were examined with undilated pupils using an EDI system of multimodality diagnostic imaging (wavelength: 870 nm; scan pattern: EDI; Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany). The image was averaged for 100 scans using the automatic averaging and eye tracking features. Measurements of macular CT were made by selecting horizontal and vertical sections going directly through the center of the fovea, as our previous studies described. 8,9 The resultant images were viewed and measured with the supplied Heidelberg Eye Explorer software (version 1.5.12.0; Heidelberg Engineering). Keratometry readings and the most recent refraction were entered into the software program to estimate optical magnification, and therefore to allow for more accurate comparisons across individuals. The CT was measured manually from the outer portion of the hyperreflective line corresponding to the RPE to the inner surface of the sclera. Choroidal thickness was measured at the subfovea, as well as at 1 and 3 mm from the fovea superiorly (S), inferiorly (I), temporally (T), and nasally (N). The choroid was measured by two independent graders who were blinded to the diagnosis. If the difference in the thickness measurements of the two examiners exceeded 15% of the mean of the two values, there was open adjudication with the senior author. 13,14 The values of the measurements were compared for each observer and then averaged for analysis. The images were obtained with the best visualization of the border between the choroid and the sclera, known as the choroidal–scleral interface (CSI). If neither image had a clearly identifiable CSI, additional images were taken to produce the best possible view of the CSI. 
Statistical Analysis
The data were processed and analyzed statistically using SPSS (Version 13.0; SPSS, Chicago, IL). Demographic data as well as clinical measurements were tabulated for all participants and by diagnostic group. The significance of differences among diagnostic groups was determined using the χ2 test for categorical variables, ANOVA for normally distributed variables, and the Kruskal-Wallis test for continuous variables that were not normally distributed. Pairwise comparisons among diagnostic groups were made by partitioning the χ2 statistic for categorical variables and using least significant difference test for continuous variables. Univariate linear regression and multivariable linear regression were used to identify participant characteristics that were associated with CT. Independent variables for the multivariable regression model with a clustering level at the individual level were chosen using the stepwise-selection method, with the criterion for inclusion in the model set at a probability value of 0.10. Adjust mean CT for the diagnostic groups were calculated and compared using analysis of covariance (ANCOVA). For all the tests, P less than 0.05 was considered to be significant. 
Results
A total of 297 subjects (eyes) were enrolled in the study: 87 were nonglaucoma controls, and 210 were AC subtype eyes classified into one of the following four groups: (1) PACS, 73 eyes, (2) APAC, 46 eyes, (3) PAC, 35 eyes, and (4) PACG, 56 eyes. The demographic and clinical examination data of the five groups are summarized in Table 1. The mean age among the five groups was similar (healthy, 58.3 years; PACS, 59.7 years; APAC, 59.8 years; PAC, 57.9 years; PACG, 59.0 years; P = 0.158). A significantly larger percentage of females occurred in the PACS, APAC, and PAC groups than in the other two groups (P < 0.001). As would be expected, AL and ACD were significantly longer in healthy eyes than in the PACS, APAC, PAC, and PACG groups (P < 0.001). The PACG group had higher IOP at imaging when compared with the other groups (P < 0.001). No significant differences were noted in DBP, SBP, MBP, DOPP, SOPP, and MOPP among the five groups. 
Table 1
 
Clinical Characteristics of the Study Subjects
Table 1
 
Clinical Characteristics of the Study Subjects
Characteristic Overall Healthy PACS APAC PAC PACG P Value*
No. of patients (no. of eyes) 297 (297) 87 (87) 73 (73) 46 (46) 35 (35) 56 (56) -
Age, y (mean, SD) 58.3 (11.7) 55.7 (14.2) 59.7 (9.6) 59.8 (9.5) 57.9 (10.0) 59.0 (11.9) 0.158
Sex (no., %)
 Male 122 (41) 49 (56) 18 (25) 15 (32) 11 (31) 29 (51) <0.001
 Female 175 (59) 38 (44) 55 (75) 31 (68) 24 (69) 27 (49)
SE, D (median, IQ) 0.27 (1.37) 0.27 (1.37) 1.03 (1.30) 0.52 (2.18) 0.25 (1.17) 0.00 (1.07) <0.001
AL, mm (mean, SD) 22.65 (0.89) 23.22 (0.80) 22.23 (0.83) 22.34 (0.90) 22.54 (0.73) 22.65 (0.69) <0.001
ACD, mm (median, IQ) 2.41 (0.68) 3.06 (0.81) 2.16 (0.36) 2.22 (0.45) 2.42 (0.45) 2.46 (0.42) <0.001
IOP at imaging, mm Hg (median, IQ) 16.0 (8.0) 16.0 (6.0) 13.0 (7.0) 18.0 (16.0) 15.0 (10.0) 24.0 (17.0) <0.001
DBP, mm Hg (mean, SD) 74.6 (9.8) 74.6 (8.5) 75.7 (10.3) 77.4 (11.3) 70.2 (8.9) 71.2 (9.4) 0.043
SBP, mm Hg (median IQ) 124.0 (21.0) 124.0 (22.0) 125.0 (24.0) 126.0 (27.0) 121.0 (17.0) 124.0 (36.0) 0.802
MBP, mm Hg (median, IQ) 90.0 (12.0) 90.0 (13.0) 91.0 (14.0) 91.0 (18.0) 87.0 (5.0) 87.0 (13.0) 0.243
DOPP, mm Hg (median, IQ) 58.0 (14.0) 59.0 (13.0) 62.0 (19.0) 59.0 (20.0) 54.0 (17.0) 40.5 (23.0) <0.001
SOPP, mm Hg (mean, SD) 108.3 (12.9) 108.3 (16.6) 114.1 (19.3) 107.1 (22.0) 104.1 (14.7) 97.6 (22.9) 0.009
MOPP, mm Hg (mean, SD) 74.6 (13.3) 75.7 (9.4) 79.5 (12.7) 75.4 (15.6) 69.6 (11.7) 60.1 (15.2) <0.001
The CT at different locations in the five groups is shown in Table 2. The mean macular CT was greatest at the subfovea. It decreased in vertical and horizontal sections, and reached a minimum of 3 mm from the fovea. Acute primary angle-closure eyes had the thickest subfoveal CT (SFCT) at 318.1 ± 88.3 μm (P < 0.05), followed by PACS, PAC, PACG, and healthy eyes. A similar pattern was also observed for SI, S3, I1, I3, N1, N3, T1, and T3 mm from the fovea. No significant differences in CT were noted between PACS and PAC eyes at any location. 
Table 2
 
Average Choroidal Thickness at Different Locations in Macula
Table 2
 
Average Choroidal Thickness at Different Locations in Macula
Location Healthy PACS APAC PAC PACG P Value*
SFCT, μm (SD) 250.7 (85.5) 291.8 (76.9) 318.1 (88.3) 291.2 (76.5) 272.8 (58.6) <0.001
S1 mm, μm (SD) 242.0 (83.1) 277.2 (73.2) 294.7 (85.2) 264.1 (64.5) 245.7 (65.3) 0.001
S3 mm, μm (SD) 239.0 (69.2) 262.5 (70.6) 276.6 (65.6) 268.9 (58.9) 245.8 (53.6) 0.012
I1 mm, μm (SD) 217.9 (82.6) 255.0 (69.1) 277.3 (78.6) 256.3 (64.8) 252.5 (63.6) <0.001
I3 mm, μm (SD) 190.3 (68.8) 226.8 (62.5) 240.5 (68.8) 225.3 (64.4) 227.2 (67.2) <0.001
N1 mm, μm (SD) 216.7 (82.3) 247.9 (82.4) 276.5 (84.7) 257.2 (78.5) 238.5 (69.6) 0.001
N3 mm, μm (SD) 144.0 (70.4) 176.6 (67.3) 191.7 (71.3) 167.6 (72.7) 171.5 (62.4) 0.002
T1 mm, μm (SD) 231.6 (77.2) 269.8 (70.7) 288.7 (77.7) 264.8 (69.5) 251.4 (59.1) <0.001
T3 mm, μm (SD) 205.6 (58.4) 250.0 (54.8) 263.7 (77.1) 238.2 (51.6) 229.1 (42.8) <0.001
Univariate regression analysis was conducted to determine parameters related to SFCT (Table 3). Diagnosis was significantly associated with SFCT (P < 0.001). Other factors significantly associated with a thinner choroid were older age (ß = −11.9, per 5-years greater, P < 0.001), longer AL (ß = −30.1, per mm greater, P < 0.001), and deeper ACD (ß = −21.2, per mm greater, P = 0.014). No correlation was noted between SFCT and other factors (sex, SE, IOP, DBP, SBP, MPP, DOPP, SOPP, and MOPP). 
Table 3
 
Subfoveal Choroidal Thickness, Univariate Analysis
Table 3
 
Subfoveal Choroidal Thickness, Univariate Analysis
Characteristic Regression Parameter (95% CI) P Value
Diagnosis
 Healthy, R 0 <0.001
 PACS 41.0 (16.0, 66.0)
 APAC 67.3 (39.0, 95.5)
 PAC 40.4 (8.8, 72.1)
 PACG 22.0 (−4.4, 48.6)
Age, per 5-y greater −11.9 (−15.7, −8.1) <0.001
Sex
 Male, R 0
 Female −6.4 (−25.6, 12.6) 0.506
SE, per D greater 6.6 (−0.5, 13.7) 0.070
AL, per mm greater −30.1 (−39.9, −20.2) <0.001
ACD, per mm greater −21.2 (−38.1, 4.3) 0.014
IOP, per 10-mm Hg greater 2.8 (−7.4, 13.1) 0.592
DBP, per 10-mm Hg greater 10.0 (−1.5, 21) 0.089
SBP, per 10-mm Hg greater 14.2 (−7.8, 4.9) 0.663
MBP, per 10-mm Hg greater 5.4 (−3.7, 14) 0.245
DOPP, per 10-mm Hg greater 4.2 (−4.6, 13) 0.347
SOPP, per 10-mm Hg greater −1.9 (−8.0, 4.0) 0.520
MOPP, per 10-mm Hg greater 1.2 (−7.4, 9.8) 0.780
Multivariate analysis including all participants identified three variables that were significantly associated with SFCT. Thinner SFCT was related to older age, longer AL, and diagnosis (with APAC subjects having a thicker choroid than the other groups) (Table 4). Even after adjusting for AL and age, diagnosis was significantly associated with SFCT (P < 0.001). Compared with the control eyes, all AC groups had thicker SFCT (all P < 0.05). Acute primary angle-closure eyes had the thickest SFCT and were 61.9-μm thicker than healthy eyes, while PACS, PAC, PACG eyes were 32.9-, 30.9-, 25.4-μm thicker, respectively, than healthy eyes. No significant difference was observed among the PACS, PAC, and PACG groups. P values of pairwise comparisons among the five groups are shown in Table 5
Table 4
 
Subfoveal Choroidal Thickness, Multivariable Analysis
Table 4
 
Subfoveal Choroidal Thickness, Multivariable Analysis
Characteristic Regression Parameter (95% CI) P Value
Age, per 5-y greater −11.6 (−15.1, −8.0) <0.001
AL, per mm greater −25.2 (−34.7, −15.7) <0.001
Diagnosis
 Healthy, R 0 <0.001
 PACS 32.9 (8.4, 57.3)
 APAC 61.9 (35.2, 88.5)
 PAC 30.9 (1.8, 60.1)
 PACG 25.4 (0.8, 50.0)
Table 5
 
Pairwise Comparison of Subfoveal Choroidal Thickness in Subtypes of Angle Closure and Healthy Control Eyes (Adjusted for Age and AL)
Table 5
 
Pairwise Comparison of Subfoveal Choroidal Thickness in Subtypes of Angle Closure and Healthy Control Eyes (Adjusted for Age and AL)
Diagnosis Healthy PACS APAC PAC PACG
Healthy - - - - -
PACS 0.009 - - - -
APAC <0.001 0.027 - - -
PAC 0.037 0.898 0.054 - -
PACG 0.043 0.558 0.009 0.722 -
Discussion
Our previous studies and other studies have demonstrated that choroidal structure and function may contribute to the pathogenesis of certain AC diseases. 8,9,15 In the present study, we used EDI-OCT to further investigate macular CT in the whole range of subtypes of AC disease by comparing the measured values with healthy control eyes. To the best of our knowledge, this is the first time that high-quality imaging modalities have been used to show the CT distribution in the whole subtypes of AC disease. 
This prospective study of 297 participants, which included 87 normals, showed that AC diagnosis was associated with a thicker choroid, while older age and longer AL were associated with a thinner choroid. Several studies investigating factors associated with CT have also demonstrated that older persons and eyes with longer AL have a thinner choroid. 16 Angle-closure eyes had a thicker choroid when compared with healthy eyes, even after adjusting for age and AL. Subfoveal choroidal thickness in all subtypes of AC (PACS, APAC, PAC, and PACG) was significantly thicker than in healthy eyes. Acute primary angle-closure eyes had the thickest CT, followed by PACS and/or PAC, PACG, and healthy eyes. No significant differences were noted in CT between PACS and PAC eyes. 
In the present study, we found that AC eyes had a greater baseline CT compared with healthy eyes. In addition to the shallow anterior chamber, shorter AL, small corneal diameter, radius of curvature, and increased lens thickness, the increased CT might be another anatomic characteristic of AC eyes. Greater baseline CT in AC eyes, leading to greater tendency to choroidal expansion, may be related to the development of AC disease. 7,17 Quigley et al. 7 hypothesized that choroidal expansion coincident with intraocular volume increase could cause an immediate increase in IOP. As aqueous humor leaves the anterior chamber to restore IOP toward normal, a pressure differential would then develop between the vitreous cavity and the posterior chamber. The lens would move forward, which would worsen the pupil block. In AC-disease eyes with a baseline narrow angle, dynamic expansion of the choroid would contribute to a greater chance for symptomatic or asymptomatic AC. 7,17  
Acute primary angle-closure eyes had the thickest CT among the five groups. A greater CT might be associated with a higher incidence of acute attacks. However, a more extensive, population-based study is needed to conform or to refute this finding. More useful information might be obtained by capturing EDI-OCT images of patients before they experience an attack of APAC in a population-based study, and subsequent images obtained during and after the attack. Uveal effusion might be another potential source of the greater CT in APAC eyes. Inflammation, hypotony, and/or sudden IOP reduction may contribute to the prevalence of uveal effusion in APAC eyes. Recent UBM studies of AC eyes show abnormal separations between the choroid and sclera, an observation that demonstrated a prevalence of uveal effusion in APAC. 18,19  
The CT in PACG eyes was thinner than in PAC eyes, although the difference was not statistically significant. In the present study, PACG eyes also had higher IOP compared with the other groups. Logically, long-term increases in IOP in PACG eyes would be expected to reduce choroidal blood volume and cause thinning of the choroid. Consistent with this hypothesis, using the water-drinking test, Arora et al. 20 found that AC eyes underwent an expansion of the choroid, but eyes with a greater IOP increase showed less choroidal expansion. 
Some potential limitations in our study should be mentioned. First, CT was greater in the APAC eyes than in the others when the IOP was reduced; however, we could not conclude that the choroidal thickening was present before or during the attack. Second, our findings are obtained from a cross-sectional comparison, so the distribution of CT in the subtypes of AC may not represent the true tendency toward variation in CT during the progression of AC disease. Well-designed longitudinal studies are needed to confirm this potential relationship. Third, in our assumptions and speculations, we considered the change in the posterior choroid to be a general change that was distributed proportionately throughout the choroid. However, quite possibly, only segmental changes were occurred in the CT. Further research is required to examine these issues. 
Conclusions
In summary, we found that AC eyes had a greater baseline CT when compared with healthy eyes, even after adjusting for age and AL. Acute primary angle-closure eyes had the thickest CT, followed by PACS and/or PAC, PACG, and healthy eyes. The increased CT might be another anatomic characteristic of AC eyes. This observation may support the hypothesis that choroidal expansion is a contributing factor to the development of AC disease. 
Acknowledgments
Supported by grants from the National Natural Science Foundation of China (81371008). 
Disclosure: W. Huang, None; W. Wang, None; X. Gao, None; X. Li, None; Z. Li, None; M. Zhou, None; S. Chen, None; X. Zhang, None 
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Footnotes
 WH and WW are joint first authors.
Table 1
 
Clinical Characteristics of the Study Subjects
Table 1
 
Clinical Characteristics of the Study Subjects
Characteristic Overall Healthy PACS APAC PAC PACG P Value*
No. of patients (no. of eyes) 297 (297) 87 (87) 73 (73) 46 (46) 35 (35) 56 (56) -
Age, y (mean, SD) 58.3 (11.7) 55.7 (14.2) 59.7 (9.6) 59.8 (9.5) 57.9 (10.0) 59.0 (11.9) 0.158
Sex (no., %)
 Male 122 (41) 49 (56) 18 (25) 15 (32) 11 (31) 29 (51) <0.001
 Female 175 (59) 38 (44) 55 (75) 31 (68) 24 (69) 27 (49)
SE, D (median, IQ) 0.27 (1.37) 0.27 (1.37) 1.03 (1.30) 0.52 (2.18) 0.25 (1.17) 0.00 (1.07) <0.001
AL, mm (mean, SD) 22.65 (0.89) 23.22 (0.80) 22.23 (0.83) 22.34 (0.90) 22.54 (0.73) 22.65 (0.69) <0.001
ACD, mm (median, IQ) 2.41 (0.68) 3.06 (0.81) 2.16 (0.36) 2.22 (0.45) 2.42 (0.45) 2.46 (0.42) <0.001
IOP at imaging, mm Hg (median, IQ) 16.0 (8.0) 16.0 (6.0) 13.0 (7.0) 18.0 (16.0) 15.0 (10.0) 24.0 (17.0) <0.001
DBP, mm Hg (mean, SD) 74.6 (9.8) 74.6 (8.5) 75.7 (10.3) 77.4 (11.3) 70.2 (8.9) 71.2 (9.4) 0.043
SBP, mm Hg (median IQ) 124.0 (21.0) 124.0 (22.0) 125.0 (24.0) 126.0 (27.0) 121.0 (17.0) 124.0 (36.0) 0.802
MBP, mm Hg (median, IQ) 90.0 (12.0) 90.0 (13.0) 91.0 (14.0) 91.0 (18.0) 87.0 (5.0) 87.0 (13.0) 0.243
DOPP, mm Hg (median, IQ) 58.0 (14.0) 59.0 (13.0) 62.0 (19.0) 59.0 (20.0) 54.0 (17.0) 40.5 (23.0) <0.001
SOPP, mm Hg (mean, SD) 108.3 (12.9) 108.3 (16.6) 114.1 (19.3) 107.1 (22.0) 104.1 (14.7) 97.6 (22.9) 0.009
MOPP, mm Hg (mean, SD) 74.6 (13.3) 75.7 (9.4) 79.5 (12.7) 75.4 (15.6) 69.6 (11.7) 60.1 (15.2) <0.001
Table 2
 
Average Choroidal Thickness at Different Locations in Macula
Table 2
 
Average Choroidal Thickness at Different Locations in Macula
Location Healthy PACS APAC PAC PACG P Value*
SFCT, μm (SD) 250.7 (85.5) 291.8 (76.9) 318.1 (88.3) 291.2 (76.5) 272.8 (58.6) <0.001
S1 mm, μm (SD) 242.0 (83.1) 277.2 (73.2) 294.7 (85.2) 264.1 (64.5) 245.7 (65.3) 0.001
S3 mm, μm (SD) 239.0 (69.2) 262.5 (70.6) 276.6 (65.6) 268.9 (58.9) 245.8 (53.6) 0.012
I1 mm, μm (SD) 217.9 (82.6) 255.0 (69.1) 277.3 (78.6) 256.3 (64.8) 252.5 (63.6) <0.001
I3 mm, μm (SD) 190.3 (68.8) 226.8 (62.5) 240.5 (68.8) 225.3 (64.4) 227.2 (67.2) <0.001
N1 mm, μm (SD) 216.7 (82.3) 247.9 (82.4) 276.5 (84.7) 257.2 (78.5) 238.5 (69.6) 0.001
N3 mm, μm (SD) 144.0 (70.4) 176.6 (67.3) 191.7 (71.3) 167.6 (72.7) 171.5 (62.4) 0.002
T1 mm, μm (SD) 231.6 (77.2) 269.8 (70.7) 288.7 (77.7) 264.8 (69.5) 251.4 (59.1) <0.001
T3 mm, μm (SD) 205.6 (58.4) 250.0 (54.8) 263.7 (77.1) 238.2 (51.6) 229.1 (42.8) <0.001
Table 3
 
Subfoveal Choroidal Thickness, Univariate Analysis
Table 3
 
Subfoveal Choroidal Thickness, Univariate Analysis
Characteristic Regression Parameter (95% CI) P Value
Diagnosis
 Healthy, R 0 <0.001
 PACS 41.0 (16.0, 66.0)
 APAC 67.3 (39.0, 95.5)
 PAC 40.4 (8.8, 72.1)
 PACG 22.0 (−4.4, 48.6)
Age, per 5-y greater −11.9 (−15.7, −8.1) <0.001
Sex
 Male, R 0
 Female −6.4 (−25.6, 12.6) 0.506
SE, per D greater 6.6 (−0.5, 13.7) 0.070
AL, per mm greater −30.1 (−39.9, −20.2) <0.001
ACD, per mm greater −21.2 (−38.1, 4.3) 0.014
IOP, per 10-mm Hg greater 2.8 (−7.4, 13.1) 0.592
DBP, per 10-mm Hg greater 10.0 (−1.5, 21) 0.089
SBP, per 10-mm Hg greater 14.2 (−7.8, 4.9) 0.663
MBP, per 10-mm Hg greater 5.4 (−3.7, 14) 0.245
DOPP, per 10-mm Hg greater 4.2 (−4.6, 13) 0.347
SOPP, per 10-mm Hg greater −1.9 (−8.0, 4.0) 0.520
MOPP, per 10-mm Hg greater 1.2 (−7.4, 9.8) 0.780
Table 4
 
Subfoveal Choroidal Thickness, Multivariable Analysis
Table 4
 
Subfoveal Choroidal Thickness, Multivariable Analysis
Characteristic Regression Parameter (95% CI) P Value
Age, per 5-y greater −11.6 (−15.1, −8.0) <0.001
AL, per mm greater −25.2 (−34.7, −15.7) <0.001
Diagnosis
 Healthy, R 0 <0.001
 PACS 32.9 (8.4, 57.3)
 APAC 61.9 (35.2, 88.5)
 PAC 30.9 (1.8, 60.1)
 PACG 25.4 (0.8, 50.0)
Table 5
 
Pairwise Comparison of Subfoveal Choroidal Thickness in Subtypes of Angle Closure and Healthy Control Eyes (Adjusted for Age and AL)
Table 5
 
Pairwise Comparison of Subfoveal Choroidal Thickness in Subtypes of Angle Closure and Healthy Control Eyes (Adjusted for Age and AL)
Diagnosis Healthy PACS APAC PAC PACG
Healthy - - - - -
PACS 0.009 - - - -
APAC <0.001 0.027 - - -
PAC 0.037 0.898 0.054 - -
PACG 0.043 0.558 0.009 0.722 -
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