Longitudinal Changes of Angle Configurationin Primary Angle-Closure SuspectsThe Zhongshan Angle-Closure Prevention Trial

Yuzhen Jiang, MSc, MD,1,2 Dolly S. Chang, MD, PhD,2,3 Haogang Zhu, MSc, PhD,1

Anthony P. Khawaja, MPhil, FRCOphth,4 Tin Aung, PhD, FRCS(Ed),5 Shengsong Huang, MSc, MD,2

Qianyun Chen, BA, MA,2 Beatriz Munoz, MSc,3 Carlota M. Grossi, BSc, PhD,1 Mingguang He, MD, PhD,1,2,*David S. Friedman, MD, PhD,2,3,6,* Paul J. Foster, PhD, FRCS(Ed)1,2,7,*

Objective: To determine longitudinal changes in angle configuration in the eyes of primary angle-closuresuspects (PACS) treated by laser peripheral iridotomy (LPI) and in untreated fellow eyes.

Design: Longitudinal cohort study.Participants: Primary angle-closure suspects aged 50 to 70 years were enrolled in a randomized, controlled

clinical trial.Methods: Each participant was treated by LPI in 1 randomly selected eye, with the fellow eye serving as a

control. Angle width was assessed in a masked fashion using gonioscopy and anterior segment optical coher-ence tomography (AS-OCT) before and at 2 weeks, 6 months, and 18 months after LPI.

Main Outcome Measures: Angle width in degrees was calculated from Shaffer grades assessed understatic gonioscopy. Angle configuration was also evaluated using angle opening distance (AOD250, AOD500,AOD750), trabecular-iris space area (TISA500, TISA750), and angle recess area (ARA) measured in AS-OCTimages.

Results: No significant difference was found in baseline measures of angle configuration between treatedand untreated eyes. At 2 weeks after LPI, the drainage angle on gonioscopy widened from a mean of 13.5� atbaseline to a mean of 25.7� in treated eyes, which was also confirmed by significant increases in all AS-OCT anglewidth measures (P<0.001 for all variables). Between 2 weeks and 18 months after LPI, a significant decrease inangle width was observed over time in treated eyes (P<0.001 for all variables), although the change over the first5.5 months was not statistically significant (P ¼ 0.07e1.00). In untreated eyes, angle width consistently decreasedacross all follow-up visits after LPI, with a more rapid longitudinal decrease compared with treated eyes (P valuesfor all variables �0.01). The annual rate of change in angle width was equivalent to 1.2�/year (95% confidenceinterval [CI], 0.8e1.6) in treated eyes and 1.6�/year (95% CI, 1.3e2.0) in untreated eyes (P<0.001).

Conclusions: Angle width of treated eyes increased markedly after LPI, remained stable for 6 months, andthen decreased significantly by 18 months after LPI. Untreated eyes experienced a more consistent and rapiddecrease in angle width over the same time period. Ophthalmology 2014;-:1e7 ª 2014 by the AmericanAcademy of Ophthalmology.

Supplemental material is available at www.aaojournal.org.

Primary angle-closure glaucoma (PACG) predominantlypresents in the form of a chronic asymptomatic condition1e3

and is estimated to be responsible for approximately half ofbinocular glaucoma blindness worldwide.4 A previouspopulation-based study reported that more than 10% ofelderly Chinese are asymptomatic suspects at risk of angle-closure.5 A considerable proportion of angle-closure suspectsare at risk of progression to primary angle-closure or PACG.6,7

Laser peripheral iridotomy (LPI), a recognized first-linetherapy for the treatment of PACG, has been demonstratedto prevent acute attacks of angle-closure in the fellow eyes ofpatients who have unilateral acute angle-closure.8e10 How-ever, no conclusive evidence has demonstrated that persons

� 2014 by the American Academy of OphthalmologyPublished by Elsevier Inc.

with asymptomatic narrow angles on gonioscopy benefit fromprophylactic LPI. Previous studies have shown that LPI opensthe drainage angle in a majority of primary angle-closuresuspects (PACS), whereas angles in a significant minority ofeyes remained closed after LPI.8,11 In the context of limitedhealthcare resources and budgets, the efficacy of prophylacticLPI needs to be demonstrated. Furthermore, the harms (if any)of prophylactic treatment need to be determined.

Since 2008, a large-scale randomized clinical trial12 (theZhongshan Angle-Closure Prevention [ZAP] trial, trialregistration information: http://www.controlled-trials.com/ISRCTN45213099; accessed January 26, 2014) was initi-ated with the purpose of assessing the efficacy and safety of

1ISSN 0161-6420/14/$ - see front matterhttp://dx.doi.org/10.1016/j.ophtha.2014.03.039

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LPI as a prophylactic measure to prevent the development ofacute or chronic primary angle-closure in asymptomaticsuspects with gonioscopically evident narrow drainage an-gles. In the current study, we analyzed the longitudinalchanges in anterior chamber angle configuration of PACSeyes in the ZAP cohort. The study design of the ZAP trial(i.e., treating 1 randomly selected eye in each participantwith LPI and using the fellow untreated eye as the control)provides a unique opportunity to compare the long-termchange of angle configuration in eyes with and withoutintervention by laser treatment. This will also help evaluatethe influence of LPI on the natural history of PACS.

Methods

Ethical approval was obtained from the Ethical Review Board ofSun Yat-sen University and the Ethical Committee of ZhongshanOphthalmic Center. The study also received institutional reviewboard approval from Moorfields Eye Hospital (via the LondonSchool of Hygiene and Tropical Medicine) and Johns HopkinsUniversity Hospital. The study was conducted in accordancewith the Tenets of the World Medical Association’s Declarationof Helsinki. Study participants were recruited from a randomizedcontrolled clinical trial, the ZAP trial (trial registration informa-tion: http://www.controlled-trials.com/ISRCTN45213099, accessedJanuary 26, 2014). The International Standard RandomizedControlled Trial Number was issued on May 6, 2008.

All examinations and interventions were carried out in theClinical Research Data Collection Center at ZhongshanOphthalmic Center, a tertiary specialized hospital in Guangzhou,South China. The field procedures for this trial have been re-ported.12 In brief, 11 991 Guangzhou citizens aged between 50 and70 years participated in the screening survey from September 2008to August 2010. Primary angle-closure suspects eligible for thisstudy were defined as those who had 6 or more clock hours ofangle circumference in which the posterior/pigmented trabecularmeshwork was not visible under static gonioscopy in both eyes,without intraocular pressure (IOP) elevated to >21 mmHg, noperipheral anterior synechiae, no glaucomatous optic neuropathy,and no evidence of anterior segment ischemia from a previousacute IOP increase. All participants underwent a darkroom proneprovocative test as part of the enrollment tests. Those who had anIOP increase greater than 15 mmHg above baseline during dark-room prone provocative test were excluded. All eligible partici-pants received LPI in 1 randomly selected eye, with the fellow eyeserving as a control. Randomization was carried out using a pre-generated list of random numbers. Each eligible participant wasassigned a number according to his/her sequence of entering thestudy. Randomization numbers and their corresponding eyeassignment were generated at the data-monitoring center at WilmerEye Institute and sent in sealed envelopes to the clinical data-collection center at Zhongshan Ophthalmic Centre.12

Detailed information on all examinations in the ZAP trial hasbeen reported.12 The limbal anterior chamber depth was assessedunder slit-lamp microscopy using a modified van Herick gradingscheme.13 The IOP was measured using Goldmann applanationtonometry (Haag-Streit AG, Koeniz, Switzerland). The median of3 readings for each eye was considered. Ocular biometricmeasures (i.e., axial length, central anterior chamber depth, andlens thickness) were acquired using ultrasound A-scan (CineScanA/B, Quantel Medical, Bozeman, MT). The width of the anteriorchamber angle was assessed using both evaluation under staticgonioscopy and quantitative measurements from images acquiredby anterior segment optical coherence tomography (AS-OCT).

2

Gonioscopy

Static gonioscopy was performed using a Goldmann-type, 1-mirrorgonioscopic lens (Haag-Streit AG) with low ambient illuminationand a 1-mm narrow beam. Gonioscopic examinations were carriedout by specialist-trained ophthalmologists (Y.J., S.H.) with highintergrader agreement (weighted kappa values for all variables>0.80).12 Gonioscopy was performed in a standardized dark roomwith low ambient illumination (<1 lux illumination by digitallight meter (measured using the Easy View model EAQ30; ExtechInstruments, Inc, Waltham, MA)) at all study visits by anexaminer who was masked to the findings collected at other visits.Care was taken to avoid the beam falling on the pupil to preventalteration of the angle configuration. If trabecular meshwork couldnot be seen because of marked iris convexity, an “over the hill”view was obtained by slightly tilting the lens toward thetrabecular meshwork without causing corneal indentation. Anglewidth was assessed under static gonioscopy using the Shaffergrading system: The width of anterior chamber angle in eachquadrant was estimated as the angle in degrees between a tangentline to the surface of the trabecular meshwork and another tangentline to the peripheral third of the iris, and then was recorded in 5-point categories (Shaffer grades 0 to 4 correspond to 0�, 10�, 20�,30�, and 40�, respectively). The range of iridotrabecular appositionalcontact observed under static gonioscopy was recorded. Peripheraliris profile was evaluated under gonioscopy and classified as beingregular, steep, plateau, or queer.14

Anterior Segment Optical Coherence Tomography

Horizontal and vertical scans of AS-OCT (Visante, Carl ZeissMeditec, Dublin, CA) were performed to obtain images of theanterior chamber angle in 4 quadrants. The AS-OCT scans werecarried out in the same standardized low ambient illumination at allstudy visits.

The AS-OCT images were quantitatively assessed using customsoftware (the Zhongshan Angle Assessment Program15) to measureangle opening distance (AOD), trabecular-iris space area (TISA),and angle recess area (ARA). Image analysis was performed by 3certified graders who were masked to the intervention assignmentand study visit. A set of 200 images from 200 eyes were randomlyselected and graded by all 3 graders independently. Good inter-grader agreement was shown by high intraclass correlation coeffi-cient (0.77e1.00). The AOD was defined as the length of a linedrawn from the anterior surface of the iris to the corneal endothelialperpendicular to the plane of the surface of the trabecular mesh-work at 250 mm, 500 mm, and 750 mm from the scleral spur(AOD250, AOD500, and AOD750, respectively).16 The TISA wasdefined as the trapezoidal area between anteriorly, AOD500 andAOD750 (TISA500 and TISA750, respectively); posteriorly, aline drawn from the scleral spur perpendicular to the plane of theinner scleral wall to the anterior surface of the iris; superiorly,the inner corneoscleral wall; and inferiorly, the anterior surface ofthe iris.17,18 The ARA was defined as the triangular area betweenthe anterior iris surface, the inner corneoscleral wall, and a lineperpendicular to the AOD750.18 Iris curvature (alternatively named“iris convexity”) was defined as the maximum perpendiculardistance between the posterior iris surface and the lineconnecting the most peripheral and the most central points of irispigment epithelium relative to the pupillary center. The IT750was defined as perpendicular iris thickness measured at 750 mmfrom the scleral spur. Mean pupil diameter of the horizontal andvertical scans acquired in the dark was recorded for each eye.Lens vault, defined as the perpendicular distance between theanterior pole of the crystalline lens and the horizontal line joiningthe 2 scleral spurs,19 was measured using AS-OCT images.

Table 1. Comparison of Baseline Measures between Treated and Untreated Eyes

Treated Eyes, Mean (95% CI) Untreated Eyes, Mean (95% CI) P Value

Angle width on gonioscopy (�) 13.5 (13.1e13.9) 13.5 (13.1e13.9) 0.87IOP (mmHg) 15.3 (15.1e15.5) 15.3 (15.1e15.5) 0.90van Herick score5% 3.5* 3.9* 0.1815% 30.7* 31.7*25% 60.9* 59.4*40% 4.4* 4.5*75% 0.5* 0.5*

Iris profileSteep 77.3* 76.7* 0.55Regular 14.5* 15.2*Plateau 8.2* 8.1*

Axial length (mm) 22.49 (22.44e22.54) 22.49 (22.44e22.54) 0.92ACD (mm) 2.54 (2.52e2.56) 2.54 (2.53e2.56) 0.73Lens thickness (mm) 4.87 (4.85e4.89) 4.87 (4.85e4.89) 0.81Appositional contacty 3.20 (2.96e3.44) 3.23 (2.98e3.47) 0.46AOD250 (mm) 63.4 (59.3e67.5) 68.1 (64.0e72.2) 0.11AOD500 (mm) 86.5 (81.9e91.2) 93.2 (88.6e97.8) 0.05AOD750 (mm) 136.4 (130.2e142.6) 142.2 (135.9e148.5) 0.20TISA500 (1000 mm2) 53.9 (51.4e56.3) 57.3 (54.8e59.7) 0.05TISA750 (1000 mm2) 96.4 (92.7e100.2) 101.3 (97.6e105.1) 0.07ARA (1000 mm2) 110.6 (105.5e115.7) 115. (111.0e121.0) 0.14

ACD ¼ central anterior chamber depth; AOD ¼ angle opening distance; ARA ¼ angle recess area; CI ¼ confidence interval; IOP ¼ intraocular pressure;TISA ¼ trabecular-iris space area.*Percentage of each category.yAppositional contact: number of clock hours in which appositional iridotrabecular contact was seen under static gonioscopy.

Jiang et al � Angle Width in PACS Treated and Untreated by LPI

Statistical Analysis

Baseline measures were compared between the treated and un-treated eyes using Wilcoxon signed-rank tests. Angle widthere-lated measures at different visits before and after LPI werecompared using 1-way repeated-measures analysis of variance,with inter-visit difference analyzed using Tukey’s method. Allstatistical analysis was performed using Stata 12 (StataCorp LP,College Station, TX).

Results

A total of 775 participants (135 men and 640 women; age (mean �standard deviation): 59.4�5.0 years) with data available from allfollow-up visits up to 18 months after LPI were included in thecurrent analysis. When comparing eyes treated by LPI with un-treated eyes, no significant difference was found in baseline fea-tures before LPI, including angle width assessed under staticgonioscopy, AS-OCT measures (i.e., AOD250, AOD500,AOD750, TISA500, TISA750, and ARA), limbal anterior chamberdepth, iris profile, ocular biometric measures, and IOP (Table 1).Of 889 participants initially recruited, 775 had data availablefrom all 4 visits when the current analysis was carried out. Nosignificant difference was found in baseline demographic andbiometric measures between included and excluded participants.The baseline Shaffer grades in the control eyes of subjects whowere excluded did not differ significantly from those included.There was a minor but statistically significant difference inbaseline Shaffer grades of treated eyes between the excluded andincluded subjects (excluded vs. included: 1.22�0.56 vs.1.35�0.60, P ¼ 0.03).

At 2 weeks after LPI, measures from both gonioscopicassessment and AS-OCT showed that the drainage angle width intreated eyes increased markedly compared with baseline (Table 2).For all eyes treated by LPI, the angle width decreased over timeexcept for the time from 2 weeks to 6 months after LPI(Tables 3 and 4, available at www.aaojournal.org; Fig 1).

In the untreated eyes, a nonsignificant increase in the anglewidth was seen on gonioscopy at 2 weeks after LPI (mean, 13.5�vs. 13.7�; P ¼ 0.68). All AS-OCT quantitative measures revealed auniformly significant increase in angle width in treated and un-treated eyes at 2 weeks after LPI (Table 2). The angle widthdecreased over time in the untreated eyes (Table 3, available atwww.aaojournal.org). The rate of narrowing of angle width inuntreated eyes was comparatively greater (treated vs. untreated:1.2�/year vs. 1.3�/year, for angle width assessed under staticgonioscopy, and P<0.001 for all variables including angle widthassessed by Shaffer grades, AOD250, AOD500, AOD750,TISA500, TISA750, and ARA) and more consistent, with nearlyall inter-visit differences being statistically significant (Tables 3and 4, available at www.aaojournal.org).

Iris curvature significantly decreased from 0.34�0.11 mmbefore LPI to 0.19�0.77 mm 2 weeks after LPI (P<0.001) intreated eyes, and then decreased to 0.15�0.23 mm 6 months post-LPI (2 vs. 6 months post-LPI: P ¼ 0.002). No significant changewas found in iris curvature from 6 to 18 months post-LPI (from0.15�0.23 mm to 0.16�0.24 mm, P ¼ 0.81). Compared with thebaseline level, IT750 decreased significantly at 2 weeks after LPI intreated eyes. No other inter-visit difference in peripheral iristhickness was found to be statistically significant (Table 5,available at www.aaojournal.org).

As shown in Table 5 (available at www.aaojournal.org), pupildiameter was found to be significantly smaller at 18 months after

3

Table 2. Change in Angle Width 2 Weeks after Laser Peripheral Iridotomy in Treated and Untreated Eyes

Treated Eyes, Mean (95% CI) Untreated Eyes, Mean (95% CI)

Change in Angle Width after LPI* P Value Change in Angle Width after LPI* P Value

Angle width (�) 12.2 (11.7e12.7) <0.001 0.1 (�0.3 to 0.6) 0.68AOD250 (mm) 37.9 (34.1e41.6) <0.001 9.7 (2.8e16.6) <0.001AOD500 (mm) 62.4 (58.0e66.9) <0.001 12.2 (5.4e19.0) <0.001AOD750 (mm) 92.9 (87.3e98.4) <0.001 13.4 (7.0e19.9) <0.001TISA500 (�1000 mm2) 24.5 (22.6e26.5) <0.001 6.4 (3.1e9.8) <0.001TISA750 (�1000 mm2) 49.4 (46.3e52.6) <0.001 10.0 (5.1e14.8) <0.001ARA (�1000 mm2) 59.4 (54.9e63.9) <0.001 17.4 (2.8e31.9) <0.001

AOD ¼ angle opening distance; ARA ¼ angle recess area; CI ¼ confidence interval; LPI ¼ laser peripheral iridotomy; TISA ¼ trabecular-iris space area.*Calculated as the value at 2 weeks after LPI minus the baseline level.

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LPI in both treated and untreated eyes compared with levels at theother 3 visits (all P values <0.05). No inter-visit difference wasfound to be statistically significant between pupil diametermeasured before LPI and 2 weeks and 6 months after LPI (Pvalues ¼ 0.145e0.999). Compared with the level at 2 weeks and 6months post-LPI, central anterior chamber depth decreased mildlybut significantly in both treated and untreated eyes (P<0.05) at 18months post-LPI (Table 5, available at www.aaojournal.org).

In treated eyes, mean lens vault increased from 924.5 mm at 2weeks post-LPI to 960.5 mm at 6 months post-LPI (P<0.001), andthen further increased to 981.7 mm at 18 months after LPI (P ¼0.012). In eyes without intervention, however, after a statisticallysignificant change in lens vault from 2 weeks to 6 months after LPI(896.1 to 930.7 mm, P<0.001), no significant increase in lens vaultover time was found. Compared with controls, eyes treated by LPIhad significantly greater lens vault at 18 months post-LPI (treatedvs. untreated: 981.7 vs. 934.0 mm, P ¼ 0.002).

Discussion

In this study of longitudinal changes of angle configurationin angle-closure suspects, we observed an overall trend ofsignificant narrowing of the anterior chamber angle overtime in both treated and untreated eyes after LPI. Themagnitude of decrease in angle width over time wassignificantly more pronounced in eyes without any inter-vention. Apart from the increase in angle width due to theelimination of pupillary block, which is an apparent benefitfrom LPI, the change of angle width after laser treatmentalso slowed down compared with the untreated eyes.

The finding of widening of the drainage angle immedi-ately after LPI is not surprising. Despite various studiessuggesting the possible existence of nonepupil blockmechanisms of angle-closure,8,20e22 pupil block is stillrecognized as a major factor in the development of primaryangle-closure. In our study, iris curvature measured in AS-OCT images significantly decreased after LPI (P<0.001).This finding was in accordance with a previous studyreporting immediate change in angle width of 176 PACSeyes after LPI,23 in which AS-OCT scans showed signifi-cant widening of the drainage angle along with reduced iriscurvature at 1 week after LPI. In contrast to the findings of aprevious study that showed a minor insignificant increase iniris curvature at 18 months compared with immediately afterLPI (0.15�0.05 mm vs. 0.16�0.06 mm, P ¼ 0.334),24 ouranalysis revealed a slight but significant decrease in iris

4

curvature from 2 weeks to 6 months post-LPI (P ¼0.002). From 6 months post-LPI, the convexity of the irisstabilized; no further significant change in iris curvature wasfound up to 18 months post-LPI (P ¼ 0.81). This result froma relatively large LPI-treated PACS cohort provides furtherevidence to the theory that nonepupil block mechanismsalso play a considerable role in causing primary angle-closure, especially in east Asians. By using the definitionof posterior/pigmented trabecular meshwork not visibleunder static gonioscopy in at least 2 quadrants, approxi-mately 25% of all eyes had persistent angle-closure afterLPI. Over the period of 2 weeks to 18 months post-LPI, thisproportion increased in both treated and untreated eyes overtime. If a more stringent definition of angle-closure (i.e.,eyes in which posterior/pigmented trabecular meshwork wasnot visible under static gonioscopy in at least 3 quadrants)was used, the proportions of eyes with persistent angle-closure at follow-up visits in the current study were allrelatively lower than the proportion reported from a previ-ous study carried out in the same geographic area.11,22

We unexpectedly found a small but significant increasein AS-OCT angle measures in eyes with no intervention at 2weeks after LPI (Table 2, Fig 1), compared with thebaseline. These significant inter-visit differences in AS-OCT measures cannot be readily explained by variationsin the quantitative analysis of AS-OCT images, because thechanges are unidirectional (i.e., increase from the baselinevisit to 2 weeks after LPI), and the graders who had highintergrader and intragrader reproducibility were masked toboth the time of image acquisition and the randomizationresult. It is possible that systemic absorption of pilocarpineadministered to the treated eye before LPI and the increasedamount of light shed on the fundus of the treated eye afterLPI might result in a certain change in pupil diameter or irisconfiguration, which then widens the drainage angle.However, no significant difference was found in pupildiameter before LPI and 2 weeks after LPI. Of note, pe-ripheral iris (measured as IT750, iris thickness at 750 mmfrom the scleral spur) was significantly thinner at 2 weeksafter LPI compared with the baseline level, but no furthersignificant change in peripheral iris thickness was detected 2weeks post-LPI (data not shown). There was also a minor0.13� increase in angle width calculated from Shaffergrades, although the change was statistically insignificant.This suggests that Shaffer grading under gonioscopy is not

Figure 1. Changes in angle width over time in treated and untreated eyes. A, Angle width assessed under static gonioscopy. B, AOD250. C, AOD500. D,AOD750. E, TISA500. F, TISA750. G, ARA. AOD ¼ angle opening distance; ARA ¼ angle recess area; CI ¼ confidence interval; TISA ¼ trabecular-irisspace area.

Jiang et al � Angle Width in PACS Treated and Untreated by LPI

5

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as quantitative and sensitive as measurements from AS-OCT images. Despite the wide acceptance of gonioscopyas the “gold standard” in morphologic observation anddetection of pathologies, the highly reproducible AS-OCTederived measurements17 may be more appropriate fordetermining small changes in quantitative analyses.

The slow decline in angle width after LPI in the PACScohort in our study is in accordance with findings of aprevious report on PACS over a similar follow-up duration,albeit in a smaller sample.24 By observing AS-OCT scans in32 PACS eyes, Lee et al24 also found an immediate increasein AOD750 and ARA after LPI and a slow reduction overtime up to 18 months after treatment. They suggested thatdecreased angle width could be due to increased lens vault(also a measure from quantitative analysis of AS-OCT im-ages, defined as the perpendicular distance between theanterior pole of the crystalline lens and the line connectingthe left and right scleral spurs on an AS-OCT scan25). In thisstudy, the direction of change in angle width after the initialpost-LPI increase was not consistent. Compared with theangle width 2 weeks after treatment, values of some vari-ables were even slightly increased at 6 months (Fig 1),although no statistically significant differences were found(Table 4, available at www.aaojournal.org). However, by18 months post-LPI, all angle width parameters haddemonstrated a decrease relative to the 2-week time-point.In agreement with findings from previous studies, we alsofound an overall trend of increase in lens vault over time inthe eyes treated by LPI and the fellow untreated eyes (datanot shown). Accordingly, in both treated and untreated eyes,central anterior chamber depth was found to be significantlysmaller at 18 months after LPI compared with other follow-up visits (Table 4, available at www.aaojournal.org). Thesesuggest that, apart from aging, there might be an additionaleffect from LPI on the bulk of the crystalline lens, especiallythe contour of its anterior surface.

There may be other explanations for the longitudinaldecrease in angle width after the initial increase after LPI.Inflammatory processes in the iris might result in changes inthe position of the ciliary processes, which may have someeffect on the drainage angle configuration. However, it isdifficult to test this assumption in the current study, becauseAS-OCT does not provide clear visualization of anatomicstructures behind the iris. Further evidence is needed fromobservation using ultrasound biomicroscopy to test thishypothesis. Another hypothesis is that the late decrease inangle width might be related to shrinkage of the iridotomy,which may compromise aqueous humor flow through it.Although data on iridotomy size were not available in thecurrent study, the curvature of the peripheral iris may serveas a surrogate measure, because it reflects the pressuregradient between the posterior and anterior chambers.However, we observed that iris curvature decreased slightlybut significantly from 0.19 mm to 0.15 mm (P ¼ 0.002)over the 18 months, rather than increasing the forwardbowing of the peripheral iris, which might be expected witha lesser-functioning iridotomy.

In conclusion, laser peripheral iridotomy resulted in amarked immediate increase in angle width in PACS, withclear evidence of the elimination of pupil block. However,

6

after several months of stabilization from 2 weeks to 6months post-LPI, drainage angles narrowed significantlyover time. A more pronounced decrease in angle width wasobserved in the untreated fellow eyes of the same cohort ofPACS.

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Footnotes and Financial Disclosures

Originally received: October 1, 2013.Final revision: March 19, 2014.Accepted: March 31, 2014.Available online: ---. Manuscript no. 2013-1654.1 UCL Institute of Ophthalmology, University College London andMoorfields Eye Hospital, London, United Kingdom.2 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center,Sun Yat-sen University, Guangzhou, China.3 Wilmer Eye Institute, Dana Center for Preventive Ophthalmology, JohnsHopkins University, Baltimore, Maryland.4 Department of Public Health and Primary Care, Institute of Public Health,University of Cambridge School of Clinical Medicine, Cambridge, UnitedKingdom.5 Singapore Eye Research Institute, Singapore National Eye Center,Singapore and National University of Singapore, Singapore.6 Department of International Health, Johns Hopkins Bloomberg School ofPublic Health, Baltimore, Maryland.7 NIHR Biomedical Research Centre at Moorfields Eye Hospital, London,United Kingdom.

*M.H., D.S.F., and P.J.F. contributed equally to this work.

Financial Disclosure(s):The author(s) have no proprietary or commercial interest in any materialsdiscussed in this article.

Supported by Fight for Sight (grant no. 1655) (United Kingdom) and theSun Yat-sen University 5010 Project Fund (grant no. 2007033) (China).Y.J. receives additional support from the British Council for Prevention ofBlindness PhD Scholarship and UCL Overseas Research Scholarship.A.P.K. is supported by a Wellcome Trust Clinical Research Fellowship(grant no. 094791/Z/10/Z). P.J.F. receives additional support from theNIHR Biomedical Research Centre at Moorfields Eye Hospital, London,United Kingdom (NIHR-BRC2 009; Moorfields/UCL-IOO), and theRichard Desmond Charitable Foundation (via Fight for Sight UK). Thesponsors or funding organizations had no roles in the design or conduct ofthis research.

Abbreviations and Acronyms:AOD ¼ angle opening distance; ARA ¼ angle recess area; AS-OCT ¼ anterior segment optical coherence tomography; CI ¼ confidenceinterval; IOP ¼ intraocular pressure; IT750 ¼ iris thickness measured at750 mm from the scleral spur; LPI ¼ laser peripheral iridotomy;PACG ¼ primary angle-closure glaucoma; PACS ¼ primary angle-closuresuspects; TISA ¼ trabecular-iris space area; ZAP ¼ Zhongshan Angle-Closure Prevention.

Correspondence:Mingguang He, MD, PhD, Department of Preventive Ophthalmology,Zhongshan Ophthalmic Center, Guangzhou 510060, People’s Republic ofChina. E-mail: mingguang_he@yahoo.com.

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