March 2013
Volume 54, Issue 3
Free
Clinical and Epidemiologic Research  |   March 2013
Relationship between Intraocular Pressure and Angle Configuration: An Anterior Segment OCT Study
Author Affiliations & Notes
  • Rachel S. Chong
    From the Singapore Eye Research Institute and Singapore National Eye Centre, Singapore; the
  • Lisandro M. Sakata
    From the Singapore Eye Research Institute and Singapore National Eye Centre, Singapore; the
    Federal University of Parana, Curitiba, Brazil; the
  • Arun K. Narayanaswamy
    From the Singapore Eye Research Institute and Singapore National Eye Centre, Singapore; the
  • Sue-Wei Ho
    From the Singapore Eye Research Institute and Singapore National Eye Centre, Singapore; the
  • Mingguang He
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China; and the
  • Mani Baskaran
    From the Singapore Eye Research Institute and Singapore National Eye Centre, Singapore; the
  • Tien Yin Wong
    From the Singapore Eye Research Institute and Singapore National Eye Centre, Singapore; the
    Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Shamira A. Perera
    From the Singapore Eye Research Institute and Singapore National Eye Centre, Singapore; the
  • Tin Aung
    From the Singapore Eye Research Institute and Singapore National Eye Centre, Singapore; the
    Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Corresponding author: Tin Aung, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751; aung_tin@yahoo.co.uk
Investigative Ophthalmology & Visual Science March 2013, Vol.54, 1650-1655. doi:10.1167/iovs.12-9986
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      Rachel S. Chong, Lisandro M. Sakata, Arun K. Narayanaswamy, Sue-Wei Ho, Mingguang He, Mani Baskaran, Tien Yin Wong, Shamira A. Perera, Tin Aung; Relationship between Intraocular Pressure and Angle Configuration: An Anterior Segment OCT Study. Invest. Ophthalmol. Vis. Sci. 2013;54(3):1650-1655. doi: 10.1167/iovs.12-9986.

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

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Abstract

Purpose.: To assess the relationship between intraocular pressure (IOP) and anterior chamber angle (ACA) configuration as assessed by gonioscopy and anterior segment optical coherence tomography (AS-OCT).

Methods.: A total of 2045 subjects aged 50 years and older, were recruited from a community clinic and underwent AS-OCT, Goldmann applanation tonometry, and gonioscopy. A quadrant was classified as closed on gonioscopy if the posterior trabecular meshwork could not be seen. A closed quadrant on AS-OCT was defined by the presence of any contact between the iris and angle wall anterior to the scleral spur. Customized software (Zhongshan Angle Assessment Program, Guangzhou, China) was used to measure AS-OCT parameters on AS-OCT scans, including anterior chamber depth, area, and volume; iris thickness (IT) and curvature; lens vault; angle opening distance; and trabecular-iris space area. IOP values were adjusted for age, sex, diabetes and hypertension status, body mass index, central corneal thickness, and presence of peripheral anterior synechiae.

Results.: Mean age of study subjects was 63.2 ± 8.0 years, 52.6% were female, and 89.4% were Chinese. Mean IOP was 14.8 ± 2.4 mm Hg (range 8–26). IOP (mean ± SE) increased with number of quadrants with gonioscopic angle closure (none: 14.6 ± 0.2; one: 14.7 ± 0.3; two: 15.0 ± 0.3; three: 15.0 ± 0.3; four: 15.6 ± 0.3 mm Hg; P < 0.001), and on AS-OCT (none: 14.7 ± 0.2; one: 15.0 ± 0.2; two: 14.8 ± 0.2; three: 15.1 ± 0.3; four: 16.0 ± 0.3 mm Hg; P < 0.001). IOP also increased in association with most of the ACA quantitative parameters measured on AS-OCT images, except for IT and lens vault.

Conclusions.: There was an association between the extent of angle closure, as assessed on AS-OCT and gonioscopy, with increasing IOP.

Introduction
Angle closure occurs in anatomically predisposed eyes in which contact between the peripheral iris and the trabecular meshwork causes mechanical impairment of aqueous outflow. This process may eventually lead to increased intraocular pressure (IOP) and ultimately glaucomatous optic neuropathy. Currently, eyes with suspected angle closure are identified based on gonioscopic assessment, which is conventionally defined as the presence of iridotrabecular contact for 180° or more. However, a few longitudinal studies have shown that only 20% of eyes considered to have gonioscopic narrow angles actually develop peripheral anterior synechiae (PAS) and/or elevated IOP over a follow-up of 3 to 5 years. 1,2 Thus, while we can identify primary angle closure suspects (PACS) who are at risk for primary angle closure glaucoma (PACG), we are still unable to identify those who will indeed develop the disease. 3,4  
As IOP is the major risk factor for the development of glaucomatous optic neuropathy, it is important to assess how the structure of the anterior chamber angle (ACA) configuration affects IOP. Foster et al. 5 have previously evaluated the determinants of IOP in a population-based study of 1232 Chinese Singaporeans, and observed a significant association between IOP and gonioscopic angle width. Aung et al. 6 evaluated 275 subjects with PACG who had undergone previous laser peripheral iridotomy (LPI), and also observed that the extent of PAS and a narrower width of the drainage angle were associated with higher untreated IOP. Both these studies used gonioscopy for ACA assessment. 5,6  
Anterior segment optical coherence tomography (AS-OCT) represents a noncontact method to obtain cross-sectional images of the ACA. These images can be used to qualitatively assess the presence of iridoangle contact, and to quantitatively measure ACA parameters. The aim of this study is to evaluate the relationship between IOP and ACA configuration, as assessed by both gonioscopy and AS-OCT, in a large community-based population from Singapore. 
Methods
In this prospective cross-sectional study, subjects aged >50 years who did not have any ophthalmic symptoms were recruited from a government-run community polyclinic providing primary health care services. This polyclinic serves >10,000 people per month, mainly of lower to middle socioeconomic status with a high proportion requiring chronic disease management. Subjects were identified by systematic sampling (every fifth patient registered at the polyclinic) and asked to participate in the study after obtaining written informed consent. This study was carried out in accordance with the Declaration of Helsinki with approval from the Institutional Review Board of the Singapore Eye Research Institute. 
After an interview to obtain previous medical and ophthalmic history, each subject underwent the following examinations on the same day: visual acuity assessment, anterior segment imaging by AS-OCT (Visante; Carl Zeiss Meditec, Dublin, CA); slit-lamp biomicroscopy; and gonioscopy. A single experienced examiner performed IOP measurements once in each eye using Goldmann applanation tonometry. The exclusion criteria were a history of glaucoma, previous intraocular surgery or penetrating eye injury, and corneal disorders, such as corneal endothelial dystrophy, corneal opacity, or pterygium, preventing ACD measurement. Subjects taking medications that could affect pupillary diameter were excluded from analysis. 
Height was measured using a wall-mounted measuring tape and weight was measured using an automatic weighing scale. Body mass index (BMI) was calculated as weight in kilograms/(height in meters). Gonioscopy was performed at the lowest level of ambient illumination that permitted a view of the angle and at high magnification (×16) by a single examiner masked to AS-OCT findings. The examiner was a trained ophthalmologist with extensive experience in performing gonioscopy in a research setting. A 1-mm beam of light was reduced to a very narrow slit and was offset vertically for assessing superior and inferior angles, and horizontally for nasal and temporal angles. Static and dynamic gonioscopy was performed using a Goldmann two-mirror lens and a Sussman four-mirror lens (both from Ocular Instruments Inc., Bellevue, WA), respectively, with the eye at the primary position of gaze. Slight tilting of the gonioscopy lens was permitted in an attempt to gain a view over the convexity of the iris. Care was taken to avoid light falling on the pupil and to avoid accidental indentation during the examination. The drainage angle in each quadrant was classified according to the Scheie grading system (based on the most posterior anatomical structure visible in the angle during nonindentation gonioscopy: grade I, ciliary body; grade II, sclera spur; grade III, anterior trabecular meshwork; grade IV, angle structures not visible) 7 to determine the number of quadrants with “angle closure”—defined as failure to visualize the posterior trabecular meshwork on nonindentation gonioscopy. PAS was defined as abnormal adhesions of the peripheral iris to the angle wall that were at least half a clock hour in width and present to the level of the anterior trabecular meshwork or higher. 
AS-OCT was performed under standardized dark conditions before any procedures that involved contact with the eye. Images of the nasal and temporal angle quadrants were captured with the participant in the sitting position and fixating on an internal target, by a single examiner masked to the other test results. The eyelids were gently retracted manually in order to obtain images of the superior and inferior angle quadrants, taking care to avoid inadvertent pressure on the globe. Three images were taken for each eye: one image scanning the angles at both the 3 and 9 o'clock–hour positions, one scanning the superior angle at 12 o'clock, and one scanning the inferior angle at 6 o'clock. 
AS-OCT images were qualitatively analyzed by two experienced examiners (TA and LMS) masked to the other results, to determine the number of quadrants with “closed angles,” defined as the presence of any contact between the iris and angle wall anterior to the scleral spur, for each subject. Quantitative analysis was performed on horizontal AS-OCT scans only using customized software (the Zhongshan Angle Analysis Program; Guangzhou, China) by a single masked observer (LMS) who identified the position of the scleral spur before the software-enabled algorithm calculated parameters of the ACA, iris, and lens. Anterior chamber depth (ACD) was defined as the distance between the endothelial surface of the cornea and the anterior surface of the lens along the visual axis. ACA was defined as the cross-sectional area of the anterior segment bounded by the endothelium, the anterior surface of iris, and the anterior surface of the lens (within the pupil). A vertical axis through the midpoint (center) of the ACA was plotted by the program, and anterior chamber volume (ACV) was calculated by rotating the ACA 360° around this vertical axis. Angle opening distance (AOD) 750 was defined as the perpendicular distance between the trabecular meshwork and the iris at 750 μm anterior to the scleral spur. Trabecular iris space area (TISA) 750 was defined as the trapezoidal area with the following boundaries: anteriorly, the AOD750; posteriorly, a line drawn from the scleral spur perpendicular to the plane of the inner scleral wall to the opposing iris; superiorly, the inner corneoscleral wall; and inferiorly, the iris surface. Lens vault (LV) was the perpendicular distance between the anterior pole of the crystalline lens and the horizontal line joining the two scleral spurs. Iris thickness (IT) 750 was defined as the iris thickness measured at 750 μm from the scleral spur. To calculate iris curvature, the software drew a line from the most peripheral to the most central point of iris pigment epithelium and then a perpendicular line that extended from this line to the iris pigment epithelium at the point of greatest convexity. Pupil diameter was defined as the distance between the most central points of the nasal and temporal iris. 
Statistical Analysis
Only right eyes were considered for analysis. Parametric and nonparametric tests were used to compare continuous variables, according to data distribution. The χ2 test was used to compare categorical data. In all analyses, IOP measurements were adjusted for age, sex, body mass index, central corneal thickness (CCT), previous diagnosis of systemic arterial hypertension and diabetes, and for the presence of PAS in order to minimize the effect of these well-known confounders in IOP measurement. Regarding the AS-OCT quantitative analysis, IOP was also adjusted for pupil diameter measured in dark conditions. Multiple regression using analysis of covariance with standard least-square analysis was performed. Well-known IOP measurements confounders were included in the model, regardless of statistical significance. The mean adjusted IOP and standard error (SE) values were obtained and compared among eyes with zero, one, two, three, and four quadrants with closed angle using ANOVA and least square mean differences using Tukey honest significance difference tests (for multiple comparisons). In the remaining analysis, the α level was set at 0.05. Statistical analyses were performed using data analysis software (JMP 5; SAS Institute, Inc., Cary, NC) and statistical analysis software (SPSS, version 13; SPSS Inc., Chicago, IL). 
Results
A total of 2114 subjects were examined from December 2005 to June 2006. Twelve subjects were ineligible because they were pseudophakic in both eyes or were known to have glaucoma and were excluded. Of the 2102 eligible subjects, 50 subjects could not complete the tests for various reasons: alignment errors (n = 12); inability to follow instructions (n = 16) or focus on the fixation light (n = 4); refused gonioscopy (n = 4); or other reasons (n = 14). A total of 2045 subjects were evaluated, of whom 1076 (52.6%) were women. Most participants were Chinese (1829 [89.4%]). The rest were Malay (150 [7.3%]); Indian (42 [2.0%]); and other races (24 [1.2%]). The mean age (SD) was 63.2 (8.0 [range, 50–93]) years. The mean IOP of the right eyes was normally distributed, with a mean IOP (SD) of 14.8 (2.4 [range, 8–26]) mm Hg. There were six subjects with problems with gonioscopy data recording, and they were excluded from all gonioscopic analysis. Only 90 subjects (4.4%) were found to have PAS on indentation gonioscopy (range 1–4 clock hours), 82 (91%) of whom showed PAS extension up to two clock hours. 
Qualitative analysis of AS-OCT images was not possible in 197 (9.6%) eyes. Comparing excluded with included subjects for this analysis, there was no significant difference for race, history of hypertension or diabetes, IOP, age, or BMI (P > 0.15). However, more men than women were excluded from this qualitative analysis (111 [5.4%] vs. 81 [4.0%], P < 0.001), and excluded subjects tended to have fewer closed quadrants on gonioscopy (0.30 [SE 0.06] vs. 0.74 [0.03], P > 0.001). Quantitative analysis of AS-OCT images was not possible in 587 (28.7%) eyes, mainly due to poor scleral spur visibility. There was no significant difference found on comparing the distribution of race, history of hypertension or diabetes, IOP, and number of closed quadrants on gonioscopy between both groups of subjects. However, excluded subjects tended to be older (mean age [SE]: 64.34 [0.33] vs. 62.72 [0.21]; P < 0.001), and had a greater BMI (BMI [SE]: 23.42 [0.15] vs. 23.97 [0.10]; P < 0.001) than included subjects. More men than women were also excluded from quantitative analysis (297 [14.6%] vs. 283 [13.9%], respectively; P = 0.03). 
After adjusting for age, sex, race, history of diabetes or hypertension, BMI, presence of PAS, and CCT, the numbers of quadrants with closed angles on gonioscopy and on AS-OCT were significantly associated with the mean adjusted IOP (Table 1, Fig. 1). The mean IOP of eyes with four quadrants with closed angles on gonioscopy was significantly higher when compared with eyes with zero and one quadrants with closed angles (P = < 0.001 and P = 0.001, respectively). For AS-OCT qualitative analysis, the mean adjusted IOP of eyes with four quadrants with closed angle was significantly higher when compared with eyes with zero, one, two, and three quadrants with closed angles (P < 0.001, P < 0.001, P < 0.001, P = 0.002, respectively). Table 2 shows the number of eyes with IOP ≥ 20 mm Hg according to the number of quadrants with closed angles, as well as the IOP range within each subgroup. Of note, all these results remained similar when eyes with PAS were excluded from the analysis (data not shown). 
Figure. 
 
Relationship between mean adjusted IOP and number of closed quadrants detected on gonioscopy (top) and AS-OCT (bottom).
Figure. 
 
Relationship between mean adjusted IOP and number of closed quadrants detected on gonioscopy (top) and AS-OCT (bottom).
Table 1. 
 
Mean Adjusted IOP in Eyes with Closed Quadrants on Gonioscopy and Qualitative AS-OCT Analysis
Table 1. 
 
Mean Adjusted IOP in Eyes with Closed Quadrants on Gonioscopy and Qualitative AS-OCT Analysis
No. of Quadrants with Closed Angles 0 Quadrants Mean Adjusted IOP (SE) 1 Quadrant Mean Adjusted IOP (SE) 2 Quadrants Mean Adjusted IOP (SE) 3 Quadrants Mean Adjusted IOP (SE) 4 Quadrants Mean Adjusted IOP (SE) P Value*
Gonioscopy, N = 2039 14.59 (0.22) 14.72 (0.29) 15.00 (0.33) 15.00 (0.28) 15.62 (0.26) <0.001
N = 1492 N = 153 N = 81 N = 140 N = 173
range (8–26) range (10–21) range (10–20) range (10–20) range (10–26)
AS-OCT, N = 1848 14.73 (0.24) 14.98 (0.25) 14.84 (0.24) 15.12 (0.28) 16.02 (0.31) <0.001
N = 791 N = 354 N = 424 N = 171 N = 108
range (8–26) range (10–21) range (10–24) range (10–23) range (10–26)
Table 2. 
 
Number of Eyes with IOP ≥ 20 mm Hg according to the Number of Quadrants with Closed Angle on Gonioscopy and AS-OCT, and the IOP Range in Each Subgroup
Table 2. 
 
Number of Eyes with IOP ≥ 20 mm Hg according to the Number of Quadrants with Closed Angle on Gonioscopy and AS-OCT, and the IOP Range in Each Subgroup
No. of Quadrants with Closed Angles 0 1 2 3 4 P Value
Gonioscopy 54/1492 (3.6%) range (8–26) 6/153 (3.9%) range (10–21) 3/81 (3.7%) range (10–20) 6/140 (4.3%) range (10–20) 18/173 (10.4%) range (10–26) <0.001
AS-OCT 29/791 (3.7%) range (8–26) 9/354 (2.5%) range (10–21) 15/424 (3.5%) range (10–24) 9/171 (5.3%) range (10–23) 15/108 (13.9%) range (10–26) <0.001
The presence of PAS on gonioscopy tended to increase with the number of quadrants with closed angles on gonioscopy (P < 0.001): zero quadrants, 6/1492 (0.4%); one quadrant, 2/153 (1.3%); two quadrants, 10/81 (12.3%); three quadrants, 30/140 (21.4%); four quadrants, 42/173 (24.3%). PAS seen on gonioscopy also tended to increase according to the number of quadrants with closed angles on AS-OCT (P < 0.001): zero quadrants, 6/790 (0.7%); one quadrant, 10/354 (0.3%); two quadrants, 38/424 (8.9%); three quadrants, 18/171 (10.5%); four quadrants, 15/108 (13.9%; P < 0.001). 
When analyzing AS-OCT quantitative parameters, ACD, ACV, AOD750, TISA750, and iris curvature (but not iris thickness or lens vault) were significantly associated with mean IOP (Table 3). These analyses were also adjusted for pupil diameter measured in dark conditions. Only analyses that showed significant IOP differences between quartiles of quantitative measurements are stated in the following sentences. Eyes with shallower ACD showed higher mean IOP values, when comparing the first versus the second quartile and the first versus the fourth quartile (both P < 0.001). Eyes with lower TISA750 also showed higher mean adjusted IOP values, particularly when comparing the first versus the second quartile and the first versus the fourth quartile (P = 0.043, P < 0.001, respectively). Eyes with more pronounced iris curvature showed higher mean IOP, as observed in the comparison between the third versus first quartile and the fourth versus the first quartile (P = 0.002, P = 0.017; respectively). Similar findings were observed with ACV and AOD750 (data not shown). Eyes with greater lens vault showed borderline higher mean IOP, as the fourth quartile showed higher IOP when compared with the first and second quartile (P = 0.024, P = 0.023, respectively). 
Table 3. 
 
Relationship between Quantitative AS-OCT Parameters and Mean IOP
Table 3. 
 
Relationship between Quantitative AS-OCT Parameters and Mean IOP
Quantitative AS-OCT Parameters A: First Quartile Mean Adjusted IOP (SE) B: Second Quartile Mean Adjusted IOP (SE) C: Third Quartile Mean Adjusted IOP (SE) D: Fourth Quartile Mean Adjusted IOP (SE) P Value*
ACD 15.15 (0.26), N = 364 14.50 (0.27), N = 367 14.87 (0.27), N = 364 14.29 (0.28), N = 365 <0.001
ACV 15.06 (0.26), N = 365 14.78 (0.27), N = 365 14.70 (0.27), N = 365 14.40 (0.28), N = 365 0.008
AOD750 15.07 (0.26), N = 365 14.71 (0.27), N = 364 14.57 (0.28), N = 364 14.31 (0.28), N = 367 0.001
TISA750 15.05 (0.26), N = 371 14.69 (0.27), N = 359 14.76 (0.28), N = 365 14.35 (0.28), N = 365 0.002
Iris thickness 750 14.73 (0.27), N = 349 14.80 (0.27), N = 360 14.82 (0.27), N = 382 14.97 (0.27), N = 368 0.703
Iris curvature 14.45 (0.28), N = 357 14.60 (0.27), N = 359 15.01 (0.26), N = 366 14.89 (0.26), N = 378 0.008
Lens vault 14.59 (0.28), N = 364 14.60 (0.28), N = 367 14.67 (0.27), N = 365 15.03 (0.26), N = 364 0.078
Pupil diameter in dark conditions was measured in all AS-OCT images in which the quantitative analysis could be performed (n = 1460). Considering the 1458 eyes with available gonioscopy and pupil measurements data, the pupil diameter was included as an independent variable in the multivariate analysis, and it did not represent a significant variable in the model (P = 0.062). Considering the 1351 eyes with available AS-OCT qualitative grading and pupil measurements data, the pupil diameter was included as an independent variable in the multivariate analysis, and it did not represent a significant variable in the model (P = 0.163). Considering the 1460 eyes with available AS-OCT quantitative and pupil measurements data, pupil diameter was included as an independent variable on the multivariate analysis, and it did represent a significant variable in the multivariate analysis that evaluated ACD, ACV, and iris curvature (P = 0.046, P = 0.033, P = 0.017, respectively), but not significantly associated in the multivariate analysis that evaluated TISA, IT, LV, and AOD750 (P = 0.112, P = 0.091, P = 0.0786, P = 0.119, respectively). 
Considering the 1848 eyes with available data from both gonioscopy and AS-OCT qualitative analysis, it was observed that AS-OCT identified more eyes with at least one quadrant with closed angles when compared with gonioscopy (1057 [57.2%] vs. 520 [28.1%], P < 0.001). 
Discussion
In this large cross-sectional study, we found that the IOP tended to increase with greater number of quadrants with closed angles as assessed using both gonioscopy and AS-OCT. These findings reflect the association between highser IOP and a narrower ACA configuration. AS-OCT is a rapid noncontact method to evaluate the ACA. However, there seems to be some disagreement in detecting rates of angle closure between AS-OCT and gonioscopy, the latter being the current clinical reference standard. In three different studies using data from three different gonioscopic examiners, AS-OCT detected approximately 50% more eyes with closed quadrants than gonioscopy. 810 In the current study, among the 1848 subjects with available data from both techniques, AS-OCT also identified more eyes with closed angles than gonioscopy (1057 [57.2%] vs. 520 [28.1%]). Nevertheless, the IOP increased in association with the number of quadrants with closed angles identified using both techniques. A significant relationship between the presence of PAS and number of quadrants of closed angles was noted in our subjects, both on gonioscopy and AS-OCT. These findings are similar to a previous paper by Foster et al., which demonstrated an association between PAS with narrow gonioscopic angles in East Asian populations. 11  
Interestingly, IOP also showed an increasing trend with decreasing ACD, anterior chamber width, and angle parameters measured by AS-OCT quantitative analysis. Notably, with smaller ACD, ACV, AOD, and TISA values, there was a significantly higher mean IOP. These results were also observed when evaluating quantitative parameters such as iris curvature and lens vault, which aim to grade the iris curvature and the relative position of the lens in the anterior chamber, respectively. Iris thickness was the only AS-OCT quantitative parameter assessed on this study that did not show an association with IOP. 
IOP is the only known modifiable risk factor for the development of glaucomatous optic neuropathy at present. In eyes with angle closure, the impairment of aqueous drainage causing raised IOP is thought to arise from several main causes: pretrabecular mechanisms, such as the direct blockage of the trabecular meshwork by the peripheral iris, or PAS; structural changes in Schlemm's canal (endothelial damage and subsequent occlusion) or trabecular meshwork (cell damage and fusion of the trabecular beams) likely secondary to the iridotrabecular contact 12,13 ; and trabecular compaction caused by increasing lens thickness and/or reduced zonular traction on the ciliary body leading to alteration in the microarchitecture of the trabecular beams. 5 The relationship between ACA appearance and its effects on the IOP is a complex one, however, as it may be influenced by many additional factors such as the height of the iridotrabecular contact; the strength in which the iris is maintained against the trabecular meshwork; the presence of iridotrabecular contact during normal daily activities (i.e., during exposure to different light conditions); characteristics of the structure and physiology of the peripheral iris tissue 14,15 ; ultrastructural changes of the trabecular meshwork and Schlemm's canal 12,13 ; and the stage of the angle closure process. 
In a previous study, Aung et al. 6 observed that post-LPI eyes with an average Shaffer grading of 0 to 1 showed a mean untreated IOP of 26.0 ± 6.4 mm Hg when compared with 24.1 ± 5.4 mm Hg in eyes with an average Shaffer grade > 1 to 2, and 21.5 ± 0.9 mm Hg in eyes with a wider angles with an average Shaffer grade > 2. There was a 0.39 mm Hg IOP increase for each unit increase in clock hours of PAS. 6 However, it is important to note that the study included subjects with more advanced disease: all PACG subjects had an untreated IOP of 21 mm Hg or more, and a mean PAS extent of 4.77 ± 3.2 clock hours (45% had more than 4 clock hours of PAS). 6 These characteristics represent subjects with established glaucomatous optic neuropathy, and already compromised aqueous drainage function. In contrast, Foster et al. 5 evaluated subjects from a population-based study and observed a significant but weak association between IOP and angle width (0.2 mm Hg per 10° change in Shaffer angle width). The authors also noted that PAS was associated with higher IOP (0.6 mm Hg increase per quadrant of drainage angle with any PAS). 6  
In the current study, the association of IOP with the numbers of quadrants with closed angles was also small. Our study sample included subjects attending a general clinic with no ophthalmological complaints and excluded all subjects with previous history of glaucoma or acute angle closure. The maximum observed IOP value was 26 mm Hg and only 4.4% of the subjects had PAS (90% of them less than 2 clock hours). The number of cases with IOP ≥ 20 mm Hg was also relatively low. Nevertheless, the presence of PAS tended to increase according to the number of quadrants with closed angles seen on both gonioscopy and AS-OCT, demonstrating an association between angle width and PAS. Interestingly, there was a greater frequency of PAS in eyes with three and four quadrants closed in gonioscopy when compared with AS-OCT (three quadrants closed: 10/81 vs. 18/171, χ2, P = 0.013; and four quadrants closed: 41/173 vs. 15/108, χ2, P = 0.05, respectively). However, in disagreement with previous studies, the presence of PAS was not significantly associated with IOP. Possible explanations are the small number of eyes with PAS and limited amount of PAS recorded in our study population. 
Our study had some limitations. A single isolated measurement of IOP was taken for each subject at varying times of the day, and it was not possible to predict future IOP behavior and progression of the angle closure process due to the cross-sectional nature of our study. A significant proportion of patients were also excluded from AS-OCT analysis due to poor visibility of the scleral spur. Although no difference regarding angle opening as assessed on gonioscopy was noted, excluded subjects tended to be men, older, and had a greater BMI. This high exclusion rate may affect the quantitative analysis results in unpredictable manners. Pupil diameter represents an important variable that may be associated with the angle opening, and it would have been interesting to check the pupil diameter in light conditions and the impact of light/dark changes on the angle opening. However, pupil diameter was only evaluated in standard dark conditions in the current study. Finally, this was not a population-based study and included mostly Chinese Singaporeans; thus, the characteristics of the study population may affect the generalizability of the results. 
In conclusion, this is the first study to suggest an association between IOP and narrower ACA parameters, as assessed by both gonioscopy and AS-OCT. Given that IOP is the only known modifiable risk factor for the treatment of glaucoma, the correlation of ocular parameters with IOP is a relevant clinical question that may influence our future management of patients at risk of developing high IOP. Longitudinal studies are needed to better understand this relationship, and to optimize the risk assessment evaluation of eyes at risk for the development of PACG. 
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Footnotes
 Supported by grants from the Biomedical Research Council, Singapore, and the National Medical Research Council, Singapore.
Footnotes
 Disclosure: R.S. Chong, None; L.M. Sakata, None; A.K. Narayanaswamy, None; S.-W. Ho, None; M. He, None; M. Baskaran, None; T.Y. Wong, None; S.A. Perera, None; T. Aung, Carl Zeiss Meditec (F, R)
Figure. 
 
Relationship between mean adjusted IOP and number of closed quadrants detected on gonioscopy (top) and AS-OCT (bottom).
Figure. 
 
Relationship between mean adjusted IOP and number of closed quadrants detected on gonioscopy (top) and AS-OCT (bottom).
Table 1. 
 
Mean Adjusted IOP in Eyes with Closed Quadrants on Gonioscopy and Qualitative AS-OCT Analysis
Table 1. 
 
Mean Adjusted IOP in Eyes with Closed Quadrants on Gonioscopy and Qualitative AS-OCT Analysis
No. of Quadrants with Closed Angles 0 Quadrants Mean Adjusted IOP (SE) 1 Quadrant Mean Adjusted IOP (SE) 2 Quadrants Mean Adjusted IOP (SE) 3 Quadrants Mean Adjusted IOP (SE) 4 Quadrants Mean Adjusted IOP (SE) P Value*
Gonioscopy, N = 2039 14.59 (0.22) 14.72 (0.29) 15.00 (0.33) 15.00 (0.28) 15.62 (0.26) <0.001
N = 1492 N = 153 N = 81 N = 140 N = 173
range (8–26) range (10–21) range (10–20) range (10–20) range (10–26)
AS-OCT, N = 1848 14.73 (0.24) 14.98 (0.25) 14.84 (0.24) 15.12 (0.28) 16.02 (0.31) <0.001
N = 791 N = 354 N = 424 N = 171 N = 108
range (8–26) range (10–21) range (10–24) range (10–23) range (10–26)
Table 2. 
 
Number of Eyes with IOP ≥ 20 mm Hg according to the Number of Quadrants with Closed Angle on Gonioscopy and AS-OCT, and the IOP Range in Each Subgroup
Table 2. 
 
Number of Eyes with IOP ≥ 20 mm Hg according to the Number of Quadrants with Closed Angle on Gonioscopy and AS-OCT, and the IOP Range in Each Subgroup
No. of Quadrants with Closed Angles 0 1 2 3 4 P Value
Gonioscopy 54/1492 (3.6%) range (8–26) 6/153 (3.9%) range (10–21) 3/81 (3.7%) range (10–20) 6/140 (4.3%) range (10–20) 18/173 (10.4%) range (10–26) <0.001
AS-OCT 29/791 (3.7%) range (8–26) 9/354 (2.5%) range (10–21) 15/424 (3.5%) range (10–24) 9/171 (5.3%) range (10–23) 15/108 (13.9%) range (10–26) <0.001
Table 3. 
 
Relationship between Quantitative AS-OCT Parameters and Mean IOP
Table 3. 
 
Relationship between Quantitative AS-OCT Parameters and Mean IOP
Quantitative AS-OCT Parameters A: First Quartile Mean Adjusted IOP (SE) B: Second Quartile Mean Adjusted IOP (SE) C: Third Quartile Mean Adjusted IOP (SE) D: Fourth Quartile Mean Adjusted IOP (SE) P Value*
ACD 15.15 (0.26), N = 364 14.50 (0.27), N = 367 14.87 (0.27), N = 364 14.29 (0.28), N = 365 <0.001
ACV 15.06 (0.26), N = 365 14.78 (0.27), N = 365 14.70 (0.27), N = 365 14.40 (0.28), N = 365 0.008
AOD750 15.07 (0.26), N = 365 14.71 (0.27), N = 364 14.57 (0.28), N = 364 14.31 (0.28), N = 367 0.001
TISA750 15.05 (0.26), N = 371 14.69 (0.27), N = 359 14.76 (0.28), N = 365 14.35 (0.28), N = 365 0.002
Iris thickness 750 14.73 (0.27), N = 349 14.80 (0.27), N = 360 14.82 (0.27), N = 382 14.97 (0.27), N = 368 0.703
Iris curvature 14.45 (0.28), N = 357 14.60 (0.27), N = 359 15.01 (0.26), N = 366 14.89 (0.26), N = 378 0.008
Lens vault 14.59 (0.28), N = 364 14.60 (0.28), N = 367 14.67 (0.27), N = 365 15.03 (0.26), N = 364 0.078
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