Pretreatment Anterior Segment Imaging During Acute Primary Angle Closure

Pretreatment Anterior Segment Imaging During Acute Primary Angle Closure Insights into Angle Closure Mechanisms in the Acute Phase Chelvin C.A. Sng, MBBChir, FRCS(Ed), 1,2 Maria Cecilia D. Aquino, MMed(Ophth), 1 Jiemin Liao, MA(App Stats), 1 Marcus Ang, MBBS, FRCS(Ed), 2 Ce Zheng, PhD, 1,2,3 Seng Chee Loon, FRCS(Ed), 1 Paul T.K. Chew, FRCOphth 1,2 Objective: To describe anterior segment optical coherence tomography (ASOCT) parameters during acute primary angle closure (APAC) before therapeutic interventions and comparative analyses of biometric parameters of APAC eyes with fellow eyes. Design: Prospective, comparative case series. Participants: Thirty-one consecutive patients with APAC. Methods: All patients underwent ASOCT imaging of both eyes during the attack, before therapeutic interventions were administered. Custom software was used to measure anterior chamber depth (ACD), anterior chamber area (ACA), anterior chamber volume (ACV), iris curvature (I-Curv), iris area (I-Area), lens vault (LV), and angle opening distance (AOD750), trabecular iris space area (TISA750), and iris thickness (IT750) at 750 mm from the scleral spur. Multivariate logistic regression modeling using forward selection was used to determine the most important biometric variables associated with APAC compared with the fellow eye during the attack. Main Outcome Measures: Anterior segment biometric parameters associated with APAC. Results: The mean age of the patients was 60.97.5 years, and 11 patients (35.5%) were male. The mean intraocular pressure was 3.89.2 mmhg in the APAC eye and 4.24.3 mmhg in the fellow eye before treatment (P < 0.001). After adjustment for pupil diameter, APAC eyes had smaller ACD, ACA, ACV, I-Curv (all P < 0.001), AOD750 (P ¼ 0.037), TISA750 (P ¼ 0.043), I-Area (P ¼ 0.027), and IT750 (P ¼ 0.002) and larger LV (P ¼ 0.041) than fellow eyes. An optimal model consisting of 3 variables (pupil diameter, ACD, and I-Curv) explained 36.7% of the variance in APAC occurrence, with ACD accounting for 18.1% and I-Curv accounting for 14.1% of this variance. Conclusions: Shallower ACD and smaller I-Curv were the 2 main anterior segment biometric parameters associated with APAC during the attack. These findings present new insights into the anterior segment biometric parameters of APAC and fellow eyes before therapeutic interventions. Anatomic changes in the anterior segment explained only about one third of the variance in APAC occurrence, and the role of nonanatomic factors require further investigation. Ophthalmology 2014;121:119-125 ª 2014 by the American Academy of Ophthalmology. Acute primary angle closure (APAC) is an ophthalmic emergency that is potentially blinding unless prompt treatment is administered to lower the markedly increased intraocular pressure (IOP). 1,2 APAC has been described as a bilateral condition with frequent early involvement of the fellow eye. 3,4 Lowe 4 reported that 58 of 113 patients with APAC experienced an acute attack in the fellow eye if prophylactic treatment was not administered, of which one third occurred within 1 year of the initial episode of APAC. 4 Consistent with this was the observation that fellow eyes of APAC had more extensive areas of iridocorneal apposition compared with primary angle closure suspect eyes, which may predispose the fellow eyes to an acute increase in IOP. 5,6 Significant differences in the anterior segment morphology have also been reported between fellow eyes of APAC and primary angle closure suspect eyes, including a reduced distance between the iris root and the angle recess, 5 shallower anterior chamber depth (ACD), narrower angle width, and a shorter distance between the trabecular meshwork and the ciliary processes in fellow eyes. 6 The biometric characteristics of APAC eyes have been shown to be well-correlated with their fellow eyes. 7 The reported morphologic similarities between APAC and fellow eyes, as well as the high rates of subsequent APAC in the fellow eyes, indicate that both the APAC eye and the fellow eye have an inherent susceptibility to an acute IOP increase. Despite this, about 90% of patients with APAC present unilaterally, with the IOP in the fellow eye within normal limits. 3 Factors significant in the initiation or activation of APAC in these predisposed eyes are currently unknown. To our knowledge, only 2 previous studies have compared APAC with fellow eyes in an attempt to identify factors that may contribute to the acute episode. 7,8 Moghimi Ó 2014 by the American Academy of Ophthalmology Published by Elsevier Inc. ISSN 0161-6420/14/$ - see front matter http://dx.doi.org/10.1016/j.ophtha.2013.08.004 119

Ophthalmology Volume 121, Number 1, January 2014 et al 8 did not observe a difference in anterior segment optical coherence tomography (ASOCT) parameters between the APAC and the fellow eye. Lim et al 7 reported that APAC eyes had shallower ACD, more anterior lens position, and less cortical opacity compared with fellow eyes. However, in both studies, patients were assessed only after laser peripheral iridotomy, which results in significant alterations in the anterior segment morphology. The ASOCT is a noncontact optical system that uses lowcoherence interferometry to obtain in vivo cross-sectional images of the entire anterior segment in 1 image frame. 9 The ASOCT allows a more objective assessment of anterior segment structures than highly subjective gonioscopy. Furthermore, customized software now allows semiautomated measurements of the anterior segment parameters with good reproducibility. 10,11 Anterior segment imaging of an APAC eye has not been performed during the attack before therapeutic interventions because patients often present as an emergency after office hours, making it logistically difficult to obtain ASOCT scans. Despite the anticipated logistic and procedural challenges, we embarked on this prospective study to determine the ocular biometric parameters of the anterior segment during an APAC attack, before laser peripheral iridotomy or medical treatment (which can alter the anterior segment measurements). 12 By comparing ASOCT parameters between the APAC and fellow eyes, we aimed to identify significant biometric parameters associated with APAC and to determine the relative significance of these parameters. Methods In this prospective study, we enrolled consecutive patients who presented with unilateral APAC to the Department of Ophthalmology at the National University Health System in Singapore. All patients were referred from the Accident and Emergency Department and immediately recruited for the study if they met the inclusion criteria outlined, and they underwent clinical evaluation with prompt ASOCT imaging before therapeutic interventions were administered. We obtained informed consent from all study subjects and ensured the safety of patients in accordance with the principles of the Declaration of Helsinki. We also obtained ethical approval from the Domain Specific Review Board of the National Healthcare Group (Singapore). Participants We included patients who presented with unilateral APAC, which was defined by the following criteria 2,13 : 1. Presence of 2 of these symptoms: headache, nausea and/ or vomiting, ocular or periocular pain, blurring of vision; 2. Presenting IOP >21 mmhg (as measured by Goldmann applanation tonometry); 3. Presence of 3 of these signs: conjunctival injection, corneal epithelial edema, shallow anterior chamber, and mid-dilated unreactive pupil; and 4. Closed anterior chamber angles in 4 quadrants found on gonioscopic examination. We excluded patients with secondary angle closure, such as iris neovascularization, lens intumescence, or subluxation and uveitis. Patients with previous ocular surgery were also excluded. Demographic data were recorded for each patient. Ophthalmic Examination Detailed slit-lamp examination of the anterior segment was performed by a fellowship-trained glaucoma specialist before any medical treatment or laser procedures were performed. Intraocular pressure was measured with Goldmann applanation tonometry, with 3 measurements performed and the mean calculated. Gonioscopy was performed with a 4-mirror goniolens (Volk Optical, Inc., Mentor, OH) with and without indentation under dark conditions. Cornea indentation was performed very briefly (<5 seconds) to determine whether the posterior trabecular meshwork was visible with indentation. A narrow beam of light (11 mm) was used to evaluate the angles, with care taken to avoid the light being directed within the pupil. The angle quadrant was classified as closed if the posterior trabecular meshwork was not visible. 14 ASOCT Imaging and Analysis Before medical treatment or laser procedures, an experienced operator performed ASOCT imaging (Visante; Carl Zeiss Meditec, Dublin, CA) of the horizontal angles in a dark room (0 lux), with the images centered on the pupil. The scans were obtained with the standard anterior segment single-scan protocol, which produces 256 scans in 0.125 seconds. The polarization was optimized, and the noise and image saturation were adjusted to obtain an image with the best quality. Several ASOCT images were obtained for each patient, and the image with the fewest artifacts was chosen for analysis. A single observer, who was masked to the clinical data, obtained measurements of the ASOCT parameters using a customized software (Anterior Segment Analysis Program, National University Hospital, Singapore). 10 The accurate identification of the scleral spurs was the only observer input required, and the algorithm then automatically calculated the anterior segment parameters (Fig 1). The ACD was defined as the axial distance from the corneal endothelium to the anterior lens surface. 10 The anterior chamber width (ACW) was defined as the distance between the 2 scleral spurs. 15 The anterior chamber area (ACA) was the cross-sectional area of the anterior chamber bordered by the posterior surface of the cornea, the anterior surface of the iris, and the anterior surface of the lens within the pupil. The software calculated anterior chamber volume (ACV) by plotting a vertical axis through the center of the ACA and rotating ACA 360 around this vertical axis. 16 Angle opening distance at 750 mm from the scleral spur (AOD750) was the perpendicular distance from the iris to the trabecular meshwork at 750 mm anterior to the scleral spur. Trabecular iris space area at 750 mm anterior to the scleral spur (TISA750) was the trapezoidal area bounded anteriorly by AOD750, posteriorly by a line perpendicular to the plane of the inner corneoscleral wall drawn from the scleral spur to the opposing iris, inferiorly by the anterior iris surface, and superiorly by the inner corneoscleral wall. 11 Iris area (I-Area) was defined as the cross-sectional area of the iris from the scleral spur to the pupil. Iris curvature (I-Curv) was the perpendicular distance from a line between the most central to the most peripheral points of the iris pigment epithelium to the posterior iris surface at the point of greatest convexity. Iris thickness at 750 mm from the scleral spur (IT750) was measured. 17e19 Lens vault (LV) was defined as the perpendicular distance from the anterior pole of the lens to the horizontal line between the scleral spurs. 20 Pupil diameter was the distance between the pupil edges of the iris. The intraclass correlation coefficient for anterior segment 120

Sng et al Anterior Segment Imaging During APAC Figure 1. Measurement of anterior segment parameters on anterior segment optical coherence tomography images using the Anterior Segment Analysis Program. ACA ¼ anterior chamber area; ACD ¼ anterior chamber depth; ACW ¼ anterior chamber width; AOD750 ¼ angle opening distance at 750 mm; I-Area ¼ iris area; I-Curv ¼ iris curvature; IT750 ¼ iris thickness at 750 mm from the scleral spur; LV ¼ lens vault; SS ¼ scleral spur; TISA750 ¼ trabecular iris space area at 750 mm. measurements using the Anterior Segment Analysis Program was >85% for all measurements in our study. Statistical Analysis Statistical analyses were performed using Stata Software version 12.1 (StataCorp LP, College Station, TX). The mean values and standard deviations were calculated for continuous data and the frequency distribution and percentages were used for categorical data for the descriptive statistics. Demographic characteristics were compared between included and excluded subjects, with the Fisher exact test used for categorical variables and the ManneWhitney U test used for continuous variables. The Wilcoxon signed-rank test was used to compare the IOP between APAC and fellow eyes. The mean values of the nasal and temporal AOD750, TISA750, I-Area, IT750, and I-Curv were calculated and used for subsequent analyses. The anterior segment measurements were compared between APAC and fellow eyes using mixed effects linear models to account for the correlation between eyes from the same individual. Data were analyzed at the eye level instead of individual level and an indicator variable for APAC status was used as an independent variable. Controlling for pupil diameter, we obtained the adjusted mean values for the anterior segment measurements in APAC eyes and fellow eyes. Adjustment for pupil diameter was performed by including it as an independent variable in the mixed models. Pupil diameter affected other anterior segment measurements significantly, especially iris parameters. Hence, previous studies investigating the association of primary angle closure with quantitative iris parameters also included pupil diameter in the logistic regression models. 17,18 To determine the most important variable that was associated with APAC, we used a forward logistic regression model, including the most significant variable at each iteration, with pupil diameter included in the model. The threshold to stop iterating was set at P < 0.05. The odds ratio was calculated for the occurrence of APAC per 0.1-mm decrease in each significant parameter. The analysis in the forward logistic regression model was repeated, with pupil diameter included as one of the variables in consideration for the iteration. The Pearson correlation coefficient was determined for the anterior segment measurements between the APAC and the fellow eye. P < 0.05 was considered significant. Results We recruited 38 consecutive patients who presented with unilateral APAC at the National University Hospital in Singapore, of which 7 patients (18.4%) were excluded owing to poor-quality ASOCT images with indeterminate scleral spurs. There were no differences in age, sex, or race between included and excluded patients. The mean age of the remaining 31 patients (81.6%) included in this study was 60.97.5 years, and 11 patients (35.5%) were male. The predominant race was Chinese (27 Chinese, 2 Malay, and 2 Indian). At presentation and before therapeutic interventions, the mean IOP was 53.89.2 mmhg in the APAC eye and 14.24.3 mmhg in the fellow eye (P < 0.001). The anterior segment angle was closed in 4 quadrants in all APAC and fellow eyes, and the posterior trabecular meshwork was not visible in all APAC eyes during cornea indentation. The anterior segment parameters of APAC and fellow eyes are compared in Table 1. After adjustment for pupil diameter, APAC eyes had smaller ACD, ACA, ACV, I-Curv (all P < 0.001), AOD750 (P ¼ 0.037), TISA750 (P ¼ 0.043), I-Area (P ¼ 0.027), and IT750 (P ¼ 0.002), as well as larger LV (P ¼ 0.041), compared with fellow eyes. The pupil diameter in APAC eyes (4.75 mm; 95% confidence interval [CI], 4.48e5.01) was greater than that in fellow eyes (4.33 mm; 95% CI, 4.04e4.62; P ¼ 0.001). Anterior segment optical coherence tomography images of 2 patients with unilateral APAC before therapeutic interventions are shown in Figure 2. In the forward logistic regression model for anterior segment parameters with the occurrence of APAC as the dependent variable (Table 2), after including pupil diameter in the model, the first iteration identified ACD as the significant factor associated with APAC (P ¼ 0.003). In the second iteration, the next most significant factor associated with APAC was I-Curv (P ¼ 0.010), after including pupil diameter and ACD in the model. In the third iteration, no other anterior segment parameters were significantly associated with APAC, after including pupil diameter, ACD, and I-Curv in the model. This model consisting of pupil diameter, ACD, and I-Curv explained 36.7% of the variance in APAC occurrence, with ACD accounting for 18.1% and I-Curv accounting for 14.1% of this variance. For every 0.1-mm decrease in ACD and I-Curv, the odds of developing APAC was 1.59 121

Ophthalmology Volume 121, Number 1, January 2014 Table 1. Comparison of Anterior Segment Optical Coherence Tomography Measurements between Acute Primary Angle Closure (APAC) and Fellow Eyes Parameter Fellow Eye APAC Eye P Value* ACD (mm) 1.91 (1.80, 2.02) 1.63 (1.54, 1.73) <0.001 ACW (mm) 11.44 (11.33, 11.56) 11.47 (11.36, 11.58) 0.515 ACA (mm 2 ) 12.87 (11.96, 13.79) 10.83 (10.03, 11.64) <0.001 ACV (mm 3 ) 74.39 (67.86, 80.92) 60.89 (55.15, 66.63) <0.001 AOD750 (mm) 0.030 (0.010, 0.050) 0.002 ( 0.015 to 0.019) 0.037 TISA750 (mm) 0.007 (0.002, 0.0114) 0.000 ( 0.004 to 0.004) 0.043 I-Area (mm 2 ) 1.70 (1.60, 1.81) 1.55 (1.46, 1.64) 0.027 IT750 (mm) 0.37 (0.35, 0.39) 0.34 (0.32, 0.36) 0.002 I-Curv (mm) 0.35 (0.31, 0.38) 0.26 (0.23, 0.29) <0.001 LV (mm) 1.06 (0.96, 1.16) 1.18 (1.09, 1.26) 0.041 ACA ¼ anterior chamber area; ACD ¼ anterior chamber depth; ACV ¼ anterior chamber volume; ACW ¼ anterior chamber width; AOD750 ¼ angle opening distance at 750 mm from the scleral spur; I-Area ¼ iris area; I-Curv ¼ iris curvature; IT750 ¼ iris thickness at 750 mm from the scleral spur; LV ¼ lens vault; TISA750 ¼ trabecular iris space area at 750 mm from the scleral spur. Data are presented as mean values (95% confidence interval). *Data adjusted for pupil diameter. (95% CI, 1.18e2.17) and 3.70 (95% CI, 1.37e10.0), respectively. Including pupil diameter as one of the variables in consideration for the iteration in the forward logistic regression model did not alter the results, and ACD and I-Curv remained the 2 most important variables associated with the occurrence of APAC; pupil diameter was not a significant independent variable. There were significant correlations for ACD (P ¼ 0.012), ACW (P < 0.001), ACA (P ¼ 0.002), ACV (P ¼ 0.002), and pupil diameter (P < 0.001) between the APAC and the fellow eye, but AOD750, TISA750, IT750, I-Area, I-Curv, and LV were not significantly correlated (Table 3). Discussion The pathogenesis of APAC is not well-understood, and the anatomic factors associated with an acute increase of IOP in predisposed eyes have not been identified. To our knowledge, this is the first study to describe the anterior segment parameters of APAC eyes during an attack, before therapeutic interventions. In this study, we have detected subtle but significant differences in several ASOCT parameters between APAC and fellow eyes at presentation, before therapeutic interventions. We also found that the 2 most significant factors associated with APAC were shallower ACD and smaller I-Curv, but these explained only about one third of the variance in APAC occurrence. Our study has provided novel data that shallower ACD and smaller I-Curv were the most important ASOCT measurements associated with the occurrence of APAC. No previous study has attempted to determine the relative significance of various anterior segment biometric parameters in association with APAC. The ACD is an important anatomic risk factor and was previously regarded as among the strongest predictors of primary angle closure glaucoma. 21,22 However, recent studies suggest that the association between angle width and ACD is confounded by other ASOCT parameters, and the correlation between angle width and ACD is not as great as it was previously thought to be. 2,23 A predictive model that included ocular biometric parameters showed that ACD was not an independent determinant of angle width in the Singapore Chinese Eye Study. 23 Nevertheless, our data indicate that ACD may be important in the development of APAC in anatomically predisposed eyes. Fellow eyes of APAC have also been reported to have shallower ACD compared with primary angle closure suspect eyes. 6,24 We found that shallower ACD was the most important anterior segment measurement associated with APAC, accounting for almost one fifth of the variance in APAC occurrence. Among people who are susceptible to APAC, it is possible that APAC occurs first in the eye with the shallower anterior chamber, although it is also possible that shallower ACD is a consequence of the increased IOP in APAC eyes. Our finding that smaller I-Curv was the second most important factor associated with APAC, accounting for 14.1% of the variance in APAC occurrence, is a novel and Figure 2. Anterior segment optical coherence tomography images of 2 patients (patients 1 and 2) with unilateral acute primary angle closure before therapeutic interventions. A, Acute primary angle closure eye. B, Fellow eye. 122

Sng et al Anterior Segment Imaging During APAC Table 2. Forward Logistic Regression Model for Anterior Segment Parameters with the Occurrence of Acute Primary Angle Closure as the Dependent Variable Parameter First Iteration P Value Second Iteration P Value Third Iteration P Value Number of Variables in Model* Odds Ratio (95% CI)/0.1-mm Decrease in Parameter Partial R 2 Model R 2 ACD (mm) 0.003 d d 2 1.59 (1.18e2.17) 0.181 0.226 ACW (mm) 0.652 0.427 0.270 d d d d ACA (mm 2 ) 0.005 0.479 0.659 d d d d ACV (mm 3 ) 0.007 0.578 0.473 d d d d AOD750 (mm) 0.209 0.451 0.415 d d d d TISA750 (mm) 0.187 0.276 0.294 d d d d I-Area (mm 2 ) 0.072 0.196 0.335 d d d d IT750 (mm) 0.027 0.603 0.194 d d d d I-Curv (mm) 0.009 0.010 d 3 3.70 (1.37e10.0) 0.141 0.367 LV 0.079 0.022 0.191 d d d d ACD ¼ anterior chamber depth; ACW ¼ anterior chamber width; ACA ¼ anterior chamber area; ACV ¼ anterior chamber volume; AOD750 ¼ angle opening distance at 750 mm from the scleral spur; CI ¼ confidence interval; I-Area ¼ iris area; I-Curv ¼ iris curvature; IT750 ¼ iris thickness at 750 mm from the scleral spur; LV ¼ lens vault; TISA750 ¼ trabecular iris space area at 750 mm from the scleral spur. *Pupil diameter included in model. surprising finding. In pupil block, the pressure differential between the anterior and posterior chambers causes the iris to adopt a convex, forward bowing configuration, 25,26 and this is measured as an increased I-Curv. Pupil block is regarded as the primary mechanism responsible for APAC 25 ; therefore, one would expect APAC eyes to have an increased I-Curv, which is contrary to our study observations. We suggest several possibilities for this discrepancy. First, the flattened iris profile may lead to an increased area of contact between the iris and the lens at the pupil margin, leading to a greater resistance to aqueous flow at the level of the pupil, initiating the attack of APAC. Second, as IOP increases in APAC eyes, the pressure in the anterior chamber would be expected to rise, thereby reducing the pressure differential between the Table 3. Correlation of Anterior Segment Biometric Characteristics Assessed Using Anterior Segment Optical Coherence Tomography between Acute Primary Angle Closure and Fellow Eyes Parameter Correlation P Value ACD (mm) 0.514 0.012 ACW (mm) 0.843 <0.001 ACA (mm 2 ) 0.617 0.002 ACV (mm 3 ) 0.615 0.002 AOD750 (mm) 0.125 0.502 TISA750 (mm) 0.120 0.520 I-Area (mm 2 ) 0.266 0.220 IT750 (mm) 0.171 0.357 I-Curv (mm) 0.333 0.120 LV (mm) 0.271 0.212 Pupil diameter (mm) 0.748 <0.001 ACD ¼ anterior chamber depth; ACW ¼ anterior chamber width; ACA ¼ anterior chamber area; ACV ¼ anterior chamber volume; AOD750 ¼ angle opening distance at 750 mm from the scleral spur; I-Area ¼ iris area; I-Curv ¼ iris curvature; IT750 ¼ iris thickness at 750 mm from the scleral spur; LV ¼ lens vault; TISA750 ¼ trabecular iris space area at 750 mm from the scleral spur. anterior and posterior chambers that causes the increased convexity of the iris. The acutely increased IOP could also lead to iris ischemia 27 and reduced I-Curv. Third, nonpupil block mechanisms, which are not associated with increased I-Curv, 10 can also cause APAC. These hypotheses are speculative and require confirmation in future studies. We also provided evidence that APAC eyes had reduced I-Area and IT750 compared with fellow eyes. This was inconsistent with the findings of Wang et al, 17 who showed that increased IT750 and I-Area were associated with a higher risk of angle closure. Our results may be explained by a decrease in iris perfusion and volume, with consequent iris ischemia secondary to the markedly raised IOP in APAC eyes. 27 Besides ACD and I-Curv, we were able to demonstrate other subtle interocular differences in anterior segment measurements between the APAC eye and the fellow eye, which were associated with the large disparity in IOP between the 2 eyes. Although these parameters were not significant, independent factors associated with the occurrence of APAC after adjusting for ACD and I-Curv, they may still be significant in anatomically predisposed individuals and may form the basis for future studies. Because the IOP was much higher in the APAC eye compared with the fellow eye at the time of ASOCT imaging, it is perhaps not surprising that we found the ACA, ACV, LV, AOD750, and TISA750 in the APAC eye to be lesser than those in the fellow eye. To our knowledge, these real-time parametric measurements and differences have not been previously recorded and described during an APAC attack. Our results suggest that, during an APAC attack, an aggregation of small but significant anatomic changes occur in the eye, either as a cause or consequence of the increased IOP. Ocular measurements performed with A-mode applanation ultrasonography showed that the ocular biometric characteristics (axial length, ACD, relative lens position, and lens thickness) between APAC and fellow eyes were wellcorrelated. 7 In our study, ASOCT imaging of the APAC and fellow eyes also demonstrated significant correlations for 123

Ophthalmology Volume 121, Number 1, January 2014 ACW, ACD, ACA, and ACV, which could explain the high incidence of APAC in the fellow eye if left untreated. 4,28 However, other ASOCT parameters were not significantly correlated between the APAC eye and the fellow eye, including the iris parameters (IT750, I-Area, and I-Curv), LV, and the measurements of angle width (AOD750 and TISA750). These interocular differences could be the cause or the consequence of acutely raised IOP in only 1 eye, despite both eyes being predisposed to APAC. Our study, which has described ASOCT parameters during an APAC attack before therapeutic interventions, has significant clinical implications. We identified small but significant interocular differences in anterior segment measurements between the APAC eye and the fellow eye. These may provide insight into the currently unknown contributory factors responsible for the initiation of APAC, or they could be changes consequent to the acutely increased IOP. Interestingly, our results show that anterior segment measurements explained only about one third of the variance in APAC occurrence. Other factors, such as medications, 29e32 postural changes, 33,34 weather conditions and the number of hours without sunshine, 35 the speed of iris constriction and dynamic iris parameters, 36,37 and choroidal expansion, 38e40 have been implicated in the pathogenesis of APAC and may be more crucial than anterior segment measurements in initiating the acute increase in IOP. Our study was limited owing to the logistical difficulties, which resulted in the small number of subjects associated with performing prompt ASOCT imaging of APAC patients before any therapeutic interventions while ensuring that patient safety was not compromised. Despite this, there was sufficient statistical power to detect significant differences in many ASOCT measurements between the APAC and the fellow eye. Because our study was cross-sectional and ASOCT imaging was performed at a single timepoint, we were unable to establish the temporal relationship between the changes in anterior segment parameters and the occurrence of APAC. However, to investigate this, anatomically predisposed eyes would need to be assessed and followed prospectively for APAC without any prophylactic interventions, which would not be ethically or logistically feasible. About one fifth of the participants were excluded for poor-quality ASOCT images and indeterminate sclera spurs, and this was comparable with other studies in which ASOCT was used to image the anterior segment. 10,11 Improvements in image acquisition and analysis would need to be made in future studies. Last, the study population was Asian and predominantly Chinese; it is unclear whether similar associations would be seen in other racial groups. In conclusion, we have presented new insights into the anterior segment biometric parameters of APAC and fellow eyes during the attack before therapeutic interventions. Shallower ACD and smaller I-Curv were the 2 most important factors associated with APAC, and we found subtle interocular differences in the anterior segment measurements between the APAC eye and the fellow eye. These novel findings have identified ocular biometric parameters that may be significant in the initiation of APAC or could be the consequence of the acutely increased IOP. Anatomic changes in the anterior segment explained only about one third of the variance in APAC occurrence, and the role of dynamic, systemic, and environmental factors should be investigated in future studies. References 1. Aung T, Friedman DS, Chew PT, et al. Long-term outcomes in Asians after acute primary angle closure. Ophthalmology 2004;111:1464 9. 2. Sng CC, See JS, Ngo CS, et al. Changes in retinal nerve fibre layer, optic nerve head morphology, and visual field after acute primary angle closure. Eye (Lond) 2011;25:619 25. 3. Edwards RS. Behaviour of the fellow eye in acute angleclosure glaucoma. Br J Ophthalmol 1982;66:576 9. 4. Lowe RF. Acute angle-closure glaucoma: the second eye: an analysis of 200 cases. Br J Ophthalmol 1962;46:641 50. 5. Sawada A, Sakuma T, Yamamoto T, Kitazawa Y. Appositional angle closure in eyes with narrow angles: comparison between the fellow eyes of acute angle-closure glaucoma and normotensive cases. J Glaucoma 1997;6:288 92. 6. Merula RV, Cronemberger S, Diniz Filho A, Calixto N. New comparative ultrasound biomicroscopic findings between fellow eyes of acute angle closure and glaucomatous eyes with narrow angle. Arq Bras Oftalmol 2008;71:793 8. 7. Lim MC, Lim LS, Gazzard G, et al. Lens opacity, thickness, and position in subjects with acute primary angle closure. J Glaucoma 2006;15:260 3. 8. 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