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Importance: Identifying primary angle closure suspect (PACS) eyes at risk of angle closure is crucial for its management. However, the risk of progression and its prediction are still understudied in long-term longitudinal studies about PACS., Objective: To explore baseline predictors and develop prediction models for the 14-year risk of progression from PACS to primary angle closure (PAC)., Design, Setting, and Participants: This cohort study involved participants from the Zhongshan Angle Closure Prevention trial who had untreated eyes with PACS. Baseline examinations included tonometry, ultrasound A-scan biometry, and anterior segment optical coherence tomography (AS-OCT) under both light and dark conditions. Primary angle closure was defined as peripheral anterior synechiae in 1 or more clock hours, intraocular pressure (IOP) greater than 24 mm Hg, or acute angle closure. Based on baseline covariates, logistic regression models were built to predict the risk of progression from PACS to PAC during 14 years of follow-up., Results: The analysis included 377 eyes from 377 patients (mean [SD] patient age at baseline, 58.28 [4.71] years; 317 females [84%]). By the 14-year follow-up visit, 93 eyes (25%) had progressed from PACS to PAC. In multivariable models, higher IOP (odds ratio [OR], 1.14 [95% CI, 1.04-1.25] per 1-mm Hg increase), shallower central anterior chamber depth (ACD; OR, 0.81 [95% CI, 0.67-0.97] per 0.1-mm increase), and shallower limbal ACD (OR, 0.96 [95% CI, 0.93-0.99] per 0.01 increase in peripheral corneal thickness) at baseline were associated with an increased 14-year risk of progression from PACS to PAC. As for AS-OCT measurements, smaller light-room trabecular-iris space area (TISA) at 500 μm from the scleral spur (OR, 0.86 [95% CI, 0.77-0.96] per 0.01-mm2 increase), smaller light-room angle recess area (ARA) at 750 μm from the scleral spur (OR, 0.93 [95% CI, 0.88-0.98] per 0.01-mm2 increase), and smaller dark-room TISA at 500 μm (OR, 0.89 [95% CI, 0.80-0.98] per 0.01-mm2 increase) at baseline were identified as predictors for the 14-year risk of progression. The prediction models based on IOP and central and limbal ACDs showed moderate performance (area under the receiver operating characteristic curve, 0.69; 95% CI, 0.63-0.75) in predicting progression from PACS to PAC, and inclusion of AS-OCT metrics did not improve the model's performance., Conclusions and Relevance: This cohort study suggests that higher IOP, shallower central and limbal ACDs, and smaller TISA at 500 μm and light-room ARA at 750 μm may serve as baseline predictors for progression to PAC in PACS eyes. Evaluating these factors can aid in customizing PACS management.

Aims: To assess dynamic change of iris area (Iarea) and volume (VOL) with physiologic pupil dilation for progression of primary angle closure suspects., Methods: Participants underwent baseline examinations including gonioscopy and anterior segment OCT (AS-OCT) as part of the Zhongshan Angle Closure Prevention Trial. The AS-OCT images were obtained both in the dark and light. Progression was defined as development of primary angle closure or an acute angle closure attack. Static ocular biometrics and dynamic changes were compared between progressors and non-progressors and multivariable logistic regression was developed to assess risk factors for progression., Results: A mean 16.8% decrease in Iarea and a mean 6.26% decrease in VOL occurred with pupil dilation, while 22.96% non-progressors and 40% progressors presented VOL increases with pupil dilation. Iarea in light and dark and VOL in light were significantly smaller in progressors. In a multivariable logistic model, older age (p=0.008), narrower horizontal angle opening distance (AOD) 250 µm from the scleral spur (AOD250, p=0.001), flatter iris curvature (IC, p=0.006) and lower loss of iris volume (ΔVOL, p=0.04) were significantly associated with progression. With receiver operating characteristic analysis, the area under the curve for ΔVOL alone was 0.621, while that for the combined index (age, AOD250, IC and ΔVOL) was 0.824. Eyes with elevated intraocular pressure had less VOL loss compared with progressors developing peripheral anterior synechiae alone (p=0.055 for ΔVOL adjusted for pupil enlargement)., Conclusion: A smaller change in ΔVOL is an additive risk factor to identify eyes more likely to develop angle closure disease., Trial Registration Number: ISRCTN45213099., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To assess the role of static and dynamic ocular biometric parameters measured in the dark and light for predicting progression of primary angle closure suspect (PACS) to primary angle closure (PAC)., Design: Retrospective cohort study using prospective randomized controlled trial data from untreated, control eyes., Methods: Zhongshan Angle Closure Prevention Trial subjects underwent anterior segment optical coherence tomography (AS-OCT) imaging in the dark and light. Static biometric parameters were measured, consisting of angle, iris, lens, and anterior chamber parameters. Dynamic change parameters were calculated by subtracting light measurements from dark measurements. Cox proportional hazards regression models were developed to assess risk factors for PACD progression., Results: A total of 861 eyes of 861 participants were analyzed (36 progressors). On univariable analysis, TISA500 measurements in the light and dark were associated with progression (P < .001), whereas dynamic change parameters were not (P ≥ .08). In the primary multivariable model, older age (hazard ratio [HR] = 1.09 per year), higher intraocular pressure (IOP) (HR = 1.13 per mm Hg), and smaller TISA500 in the light (HR = 1.28 per 0.01 mm 2 ) were significantly associated with greater risk of progression (P ≤ .04). Dark TISA500 had similar significance (HR = 1.28, P = .002) when replacing light TISA500. Risk of progression was more predictive among eyes in the lowest quartile of light TISA500 measurements (HR = 4.56, P < .001) compared to dark measurements (HR = 2.89, P = .003)., Conclusion: Static parameters measured in the light are as predictive, and possibly more so, of angle closure progression as those measured in the dark. Ocular biometrics measured under light and dark conditions may provide additional information for risk-stratifying patients for angle closure progression., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Angle-closure is responsible for half of all glaucoma blindness globally. Patients with suspected glaucoma require assessment of the drainage angle by an experienced clinician. The goal of this study is to evaluate the diagnostic performance and cost-effectiveness of two non-contact tests, anterior segment OCT (Optical Coherence Tomography) (AS-OCT) and limbal anterior chamber depth for patients referred to hospital with suspected angle closure compared with gonioscopy by ophthalmologist., Methods and Analysis: Study design: prospective, multicentre, cross-sectional diagnostic accuracy study., Inclusion Criteria: adults referred from community optometry to hospital with suspected angle closure., Primary Outcome: Sensitivity and specificity., Secondary Outcomes: Positive/negative likelihood ratios, concordance, cost-effectiveness, proportion of patients requiring subsequent clinical assessment by ophthalmologist., Sample Size: 600 individuals who have been referred with suspected angle closure from primary care (community optometry). We will have a 95% probability of detecting the true sensitivity of either test to within ±3.5% based on a sensitivity of 90%. The study would also have a 95% probability of detecting the true specificity of either test to within ±5%, assuming a specificity of 75%., Ethics and Dissemination: Ethical Review Board approval was obtained. REC reference: 22/LO/0885. Our findings will be disseminated to those involved in eye care services. We will have a knowledge exchange event at the end of the study, published via the Health Technology Assessment web page and in specialist journals. The results will be presented at professional conferences and directly to patients via patient group meetings and the Glaucoma UK charity., Trial Registration Number: ISRCTN15115867., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background/aims: Prophylactic laser peripheral iridotomy (LPI) is performed in primary angle-closure suspect (PACS) eyes to prevent acute angle-closure attacks. However, accelerated cataractogenesis is a potential risk of the procedure that may result in decreased visual acuity. We aimed to assess the long-term impact of LPI on cataract formation in Chinese PACS., Methods: In the Zhongshan Angle Closure Prevention Trial, eligible bilateral PACS participants received LPI in one randomly selected eye, while the fellow eye remained untreated. Cataract was graded using the Lens Opacity Classification System III, and progression was defined as an increase in grade by at least two units in any category or cataract surgery., Results: In total, 889 participants were randomly assigned to LPI in one eye only (mean age 59±5 years, 83% female). At 72 months, treated eyes had slightly higher average nuclear grades (p<0.001). However, there were no differences between eyes for predefined cataract progression (cumulative probability at 72 months: 21.2% in LPI vs 19.4% in control, p=0.401) or cataract surgery (1% for both). While LPI-treated eyes had a 10% higher risk of progression over 6 years (HR=1.10 (95% CI 0.88 to 1.36)), this was not statistically significant. Visual acuity at 72 months was similar in treated and untreated eyes (p=0.43)., Conclusion: Although lenses were graded on average as slightly more opaque in laser-treated eyes, prophylactic neodymium:yttrium-aluminum-garnet LPI did not cause significant cataract progression. Our results suggest that LPI treatment of asymptomatic narrow angles does not increase the risk of developing clinically meaningful cataract worsening over time., Trial Registration Number: ISRCTN45213099., Competing Interests: Competing interests: DS-TC and JAK are employees of Genentech Inc., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This study aimed to evaluate the efficacy of laser peripheral iridotomy (LPI) prophylaxis for patients with primary angle-closure suspect (PACS) after 14 years and to identify risk factors for the conversion from PACS to primary angle closure (PAC)., Design: Extended follow-up of the Zhongshan Angle-Closure Prevention Study., Participants: Eight hundred eighty-nine Chinese patients 50 to 70 years of age with bilateral PACS., Methods: Each patient received LPI in 1 randomly selected eye, with the fellow untreated eye serving as a control. Because the risk of glaucoma was low and acute angle closure (AAC) occurred only rarely, the follow-up was extended to 14 years despite substantial benefits of LPI reported after the 6-year visit., Main Outcome Measures: Incidence of PAC, a composite end point including peripheral anterior synechiae, intraocular pressure (IOP) of > 24 mmHg, or AAC., Results: During the 14 years, 390 LPI-treated eyes and 388 control eyes were lost to follow-up. A total of 33 LPI-treated eyes and 105 control eyes reached primary end points (P < 0.01). Within them, 1 LPI-treated eye and 5 control eyes progressed to AAC. Primary angle-closure glaucoma was found in 2 LPI-treated eyes and 4 control eyes. The hazard ratio for progression to PAC was 0.31 (95% confidence interval, 0.21-0.46) in LPI-treated eyes compared with control eyes. At the 14-year visit, LPI-treated eyes showed more severe nuclear cataract, higher IOP, and larger angle width and limbal anterior chamber depth (LACD) than control eyes. Higher IOP, shallower LACD, and greater central anterior chamber depth (CACD) were associated with an increased risk of end points developing in control eyes. In the treated group, eyes with higher IOP, shallower LACD, or less IOP elevation after the darkroom prone provocative test (DRPPT) were more likely to demonstrate PAC after LPI., Concluions: Despite a two-third decrease in PAC occurrence after LPI, the cumulative risk of progression was relatively low in the community-based PACS population over 14 years. Apart from IOP, IOP elevation after DRPPT, CACD, and LACD, more risk factors are needed to achieve precise prediction of PAC occurrence and to guide clinical practice., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background/aims: To assess baseline ocular parameters in the prediction of long-term intraocular pressure (IOP) control after clear lens extraction (CLE) or laser peripheral iridotomy (LPI) in patients with primary angle closure (PAC) disease using data from the Effectiveness of Early Lens Extraction for the treatment of primary angle-closure glaucoma (EAGLE) tria., Methods: This study is a secondary analysis of EAGLE data where we define the primary outcome of 'good responders' as those with IOP<21 mm Hg without requiring additional surgery and 'optimal responders' as those who in addition were medication free, at 36-month follow-up. Primary analysis was conducted using a multivariate logistic regression model to assess how randomised interventions and ocular parameters predict treatment response., Results: A total of 369 patients (182 in CLE arm and 187 in LPI arm) completed the 36-month follow-up examination. After CLE, 90% met our predefined 'good response' criterion compared with 67% in the LPI arm, and 66% met 'optimal response' criterion compared with 18% in the LPI arm, with significantly longer drops/surgery-free survival time (p<0.05 for all). Patients randomised to CLE (OR=10.1 (6.1 to 16.8)), Chinese (OR=2.3 (1.3 to 3.9)), and those who had not previously used glaucoma drops (OR=2.8 (1.6 to 4.8)) were more likely to maintain long-term optimal IOP response over 36 months., Conclusion: Patients with primary angle closure glaucoma/PAC are 10 times more likely to maintain drop-free good IOP control with initial CLE surgery than LPI. Non-Chinese ethnicity, higher baseline IOP and using glaucoma drops prior to randomisation are predictors of worse long-term IOP response., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Laser peripheral iridotomy (LPI) is the most common primary treatment for primary angle closure disease (PACD). However, there are sparse data guiding the longitudinal care of PAC suspect (PACS) eyes after LPI., Objective: To elucidate the anatomic effects of LPI that are associated with a protective outcome against progression from PACS to PAC and acute angle closure (AAC) and to identify biometric factors that predict progression after LPI., Design, Setting, and Participants: This was a retrospective analysis of data from the Zhongshan Angle Closure Prevention (ZAP) trial, a study of mainland Chinese people aged 50 to 70 years with bilateral PACS who received LPI in 1 randomly selected eye. Gonioscopy and anterior-segment optical coherence tomography (AS-OCT) imaging were performed 2 weeks after LPI. Progression was defined as the development of PAC or an acute angle closure (AAC) attack. Cohort A included a random mix of treated and untreated eyes, and cohort B included only eyes treated with LPI. Univariable and multivariable Cox regression models were developed to assess biometric risk factors for progression in cohorts A and B. Data were analyzed from January 4 to December 22, 2022., Main Outcome and Measure: Six-year progression to PAC or AAC., Results: Cohort A included 878 eyes from 878 participants (mean [SD] age, 58.9 [5.0] years; 726 female [82.7%]) of whom 44 experienced progressive disease. In a multivariable analysis, treatment (hazard ratio [HR], 0.67; 95% CI, 0.34-1.33; P = .25) was no longer associated with progression after adjusting for age and trabecular iris space area at 500 μm (TISA at 500 μm) at the 2-week visit. Cohort B included 869 treated eyes from 869 participants (mean [SD] age, 58.9 [5.0] years; 717 female [82.5%]) of whom 19 experienced progressive disease. In multivariable analysis, TISA at 500 μm (HR, 1.33 per 0.01 mm2 smaller; 95% CI, 1.12-1.56; P = .001) and cumulative gonioscopy score (HR, 1.25 per grade smaller; 95% CI, 1.03-1.52; P = .02) at the 2-week visit were associated with progression. Persistent angle narrowing on AS-OCT (TISA at 500 μm ≤0.05 mm2; HR, 9.41; 95% CI, 3.39-26.08; P <.001) or gonioscopy (cumulative score ≤6; HR, 2.80; 95% CI, 1.13-6.93; P =.04) conferred higher risk of progression., Conclusions and Relevance: Study results suggest that persistent angle narrowing detected by AS-OCT or cumulative gonioscopy score was predictive of disease progression in PACS eyes after LPI. These findings suggest that AS-OCT and gonioscopy may be performed to identify patients at high risk of developing angle closure who may benefit from closer monitoring despite patent LPI.

Purpose: Angle-closure glaucoma is a major cause of blindness worldwide that carries an excessive risk of severe, bilateral visual impairment. A common concern among clinicians is the precipitation of acute angle-closure (AAC) attacks because of mydriasis. We evaluated the risk of AAC after pharmacologic dilation in Chinese individuals classified as having bilateral primary angle-closure suspects (PACSs)., Design: Randomized, interventional, controlled trial., Participants: A total of 889 patients with bilateral PACSs, aged between 50 and 70 years, were identified through community screening in Guangzhou, China, and enrolled in the study., Methods: In the Zhongshan Angle-Closure Prevention Trial, bilateral PACSs were treated with laser peripheral iridotomy (LPI) in 1 randomly selected eye, with the fellow eye serving as an untreated control. Over 72 months of follow-up, the participants had their pupils pharmacologically dilated 6 times with 5% phenylephrine and 0.5% tropicamide., Main Outcome Measures: Incidence and risk of post-mydriasis AAC in LPI-treated and untreated, control eyes classified as PACSs., Results: One bilateral AAC attack occurred after mydriasis at the 2-week post-LPI visit. No other AAC events occurred in the LPI-treated eyes. In the untreated eyes, 4 additional attacks occurred: 2 occurred after dilation (1 at 54 months and 1 at 72 months of follow-up) and 2 occurred spontaneously. The risk of post-mydriasis AAC in the untreated eyes was 1 attack in 1587 dilations. The risk of spontaneous AAC in the untreated eyes was 0.44 per 1000 eye-years (95% confidence interval, 0.11-1.77 per 1000 eye-years)., Conclusions: The risk of incident AAC attacks in PACSs was extremely low, even in a higher-risk group that underwent repeated pharmacologic pupillary dilation over 6 years of follow-up. Prophylactic LPI reduced this small but real risk. This trial was registered at ISRCTN.com as ISRCTN45213099., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess baseline ocular biometric risk factors for progression from primary angle closure suspect (PACS) to primary angle closure (PAC) or acute angle closure (AAC)., Design: Prospective, observational study., Participants: Six hundred forty-three mainland Chinese with untreated PACS., Methods: Participants underwent baseline clinical examinations, including gonioscopy, anterior segment OCT (AS-OCT) imaging, and A-scan ultrasound biometry as part of the Zhongshan Angle Closure Prevention (ZAP) Trial. Primary angle closure suspect was defined as an inability to visualize pigmented trabecular meshwork in 2 or more quadrants based on static gonioscopy. Primary angle closure was defined as development of intraocular pressure above 24 mmHg or peripheral anterior synechiae. Progression was defined as development of PAC or an AAC attack. Multivariable logistic regression models were developed to assess biometric risk factors for progression., Main Outcome Measures: Six-year progression from PACS to PAC or AAC., Results: Six hundred forty-three untreated eyes (609 nonprogressors, 34 progressors) of 643 participants were analyzed. In a multivariable model with continuous parameters, narrower horizontal angle opening distance of 500 μm from the scleral spur (AOD 500 ; odds ratio [OR], 1.10 per 0.01-mm decrease; P = 0.03), flatter horizontal iris curvature (IC; OR, 1.96 per 0.1-mm decrease; P = 0.01), and older age (OR, 1.11 per 1-year increase; P = 0.01) at baseline were associated significantly with progression (area under the receiver operating characteristic curve [AUC], 0.73). Smaller cumulative gonioscopy score was not associated with progression (OR, 1.03 per 1-modified Shaffer grade decrease; P = 0.85) when replacing horizontal AOD 500 in the multivariable model. In a separate multivariable model with categorical parameters, participants in the lowest quartile of horizontal AOD 500 (OR, 3.10; P = 0.002) and IC (OR, 2.48; P = 0.014) measurements and 59 years of age or older (OR, 2.68; P = 0.01) at baseline showed higher odds of progression (AUC, 0.72)., Conclusions: Ocular biometric measurements can help to risk-stratify patients with early angle closure for more severe disease. Anterior segment OCT measurements of biometric parameters describing the angle and iris are predictive of progression from PACS to PAC or AAC, whereas gonioscopy grades are not., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine the efficacy of laser peripheral iridotomy (LPI) in patients who received a diagnosis of primary angle-closure suspect (PACS)., Design: Prospective, randomized controlled trial., Participants: This multicenter, randomized controlled trial (ClinicalTrials.gov identifier, NCT00347178) enrolled 480 patients older than 50 years from glaucoma clinics in Singapore with bilateral asymptomatic PACS (defined as having ≥2 quadrants of appositional angle closure on gonioscopy)., Methods: Each participant underwent prophylactic LPI in 1 randomly selected eye, whereas the fellow eye served as a control. Patients were followed up yearly for 5 years., Main Outcome Measures: The primary outcome measure was development of primary angle closure (PAC; defined as presence of peripheral anterior synechiae, intraocular pressure [IOP] of >21 mmHg, or both or acute angle closure [AAC]) or primary angle-closure glaucoma (PACG) over 5 years., Results: Of the 480 randomized participants, most were Chinese (92.7%) and were women (75.8%) with mean age of 62.8 ± 6.9 years. Eyes treated with LPI reached the end point less frequently after 5 years (n = 24 [5.0%]; incidence rate [IR], 11.65 per 1000 eye-years) compared with control eyes (n = 45 [9.4%]; IR, 21.84 per 1000 eye-years; P = 0.001). The adjusted hazard ratio (HR) for progression to PAC was 0.55 (95% confidence interval [CI], 0.37-0.83; P = 0.004) in LPI-treated eyes compared with control eyes. Older participants (per year; HR, 1.06; 95% CI, 1.03-1.10; P < 0.001) and eyes with higher baseline IOP (per millimeter of mercury; HR, 1.35; 95% CI, 1.22-1.50; P < 0.0001) were more likely to reach an end point. The number needed to treat to prevent an end point was 22 (95% CI, 12.8-57.5)., Conclusions: In patients with bilateral asymptomatic PACS, eyes that underwent prophylactic LPI reached significantly fewer end points compared with control eyes over 5 years. However, the overall incidence of PAC or PACG was low., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess anatomic changes after laser peripheral iridotomy (LPI) and predictors of angle widening based on anterior segment (AS) OCT and angle opening based on gonioscopy., Design: Prospective observational study., Participants: Primary angle-closure suspects (PACSs) 50 to 70 years of age., Methods: Participants of the Zhongshan Angle Closure Prevention (ZAP) Trial underwent gonioscopy and AS-OCT imaging at baseline and 2 weeks after LPI. Primary angle-closure suspect was defined as the inability to visualize pigmented trabecular meshwork in 2 or more quadrants on static gonioscopy. Laser peripheral iridotomy was performed on 1 eye per patient in superior (between 11 and 1 o'clock) or temporal or nasal locations (at or below 10:30 or 1:30 o'clock). Biometric parameters in horizontal and vertical AS-OCT scans were measured and averaged. Linear and logistic regression modeling were performed to determine predictors of angle widening, defined as change in mean angle opening distance measured at 750 μm from the scleral spur (AOD 750 ); poor angle widening, defined as the lowest quintile of change in mean AOD 750 ; and poor angle opening, defined as residual PACS after LPI based on gonioscopy., Main Outcome Measures: Anatomic changes and predictors of angle widening and opening after LPI., Results: Four hundred fifty-four patients were included in the analysis. Two hundred nineteen underwent superior LPI and 235 underwent temporal or nasal LPI. Significant changes were found among most biometric parameters (P < 0.006) after LPI, including greater AOD 750 (P < 0.001). One hundred twenty eyes (26.4%) showed residual PACS after LPI. In multivariate regression analysis, superior LPI location (P = 0.004), smaller AOD 750 (P < 0.001), and greater iris curvature (P < 0.001), were predictive of greater angle widening. Temporal or nasal LPI locations (odds ratio [OR], 2.60, P < 0.001) was predictive of poor angle widening. Smaller mean gonioscopy grade (OR, 0.34, 1-grade increment) was predictive of poor angle opening., Conclusions: Superior LPI location results in significantly greater angle widening compared with temporal or nasal locations in a Chinese population with PACS. This supports consideration of superior LPI locations to optimize anatomic changes after LPI., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

We report cases of acute angle closure in 2 young highly myopic siblings with Knobloch syndrome. To our knowledge, this is the first report of acute angle closure in Knobloch syndrome. Both patients were homozygous for a likely pathogenic variant in COL18A1. Both responded to treatment with cyclophotocoagulation and remained stable despite declining or being medically unfit for clear lens extraction. We argue that the recent implication of heterozygous mutations in COL18A1 in familial angle closure supports the argument that acute angle closure in these 2 patients was likely to be a thus far unreported feature of Knobloch syndrome. In addition, these cases also support the hypothesis that pathogenic variants in COL18A1 may be a risk factor for acute angle closure., Competing Interests: Funding: Great Ormond Street Childrens’ Charity. Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purposes: To evaluate the effect of YAG laser peripheral iridotomy (LPI) on corneal endothelial cell density (ECD) and morphology in primary angle closure suspects (PACS) over 72 months., Methods: The Zhongshan Angle Closure Prevention Trial is a single-centre randomised controlled trial. Subjects with bilateral PACS received YAG LPI prophylactic treatment in one eye randomly, while the fellow eye served as control. Central corneal ECD and morphology were assessed using non-contact specular microscopy (SP-2000P, Topcon) at baseline, 6, 18, 36, 54 and 72 months postoperatively. Mixed model analysis was conducted to compare the difference between treated and fellow eyes., Results: A total of 875 participants were included, with a mean age of 59.3±5.0 years and 83.5% female. The ECD declined significantly (p<0.001) over time in both treated and fellow eyes, but the treated eyes showed more progressive cell loss with increasing time (p<0.001). The difference in ECD loss between LPI-treated and fellow eyes was not significant at each follow-up until 72 months (4.9% in LPI eyes vs 4.2% in non-LPI eyes, p=0.003). Mean cell areas increased significantly over time in both treated and fellow eyes (p<0.001), but no longitudinal change was observed for hexagonality. In LPI-treated eyes, no significant correlation was found between age, gender, ocular biometrics, intraocular pressure and laser settings with endothelium change, except for time effect (p<0.01)., Conclusion: ECD decreases over time primarily due to ageing effect. YAG LPI does not appear to cause clinically significant corneal endothelial damage over 72 months after treatment., Trial Registration Number: ISRCTN45213099., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Angle-closure glaucoma is an aggressive condition that causes millions to become blind worldwide. This review explores the use of prophylactic laser peripheral iridotomy (PI) in patients classified as primary angle-closure suspects (PACS), and additionally, the use of clear lens exchange as a primary treatment option in established angle-closure disease with or without glaucoma. As PI has a strong prophylactic effect in fellow eyes of patients who have had an acute attack, its use has been widely adopted in those patients classified as PACS, but with limited evidence to support this. A large randomised trial conducted in China has demonstrated that although PI reduces the risk of incident angle-closure disease, the incidence of disease that would threaten vision was much lower than anticipated. This suggests that the benefit of prophylactic PI is very limited. Health services data shows an association between rising cataract surgical rates and of decreasing rates of acute angle-closure. Age-related growth of the lens is a major component of angle-closure disease. Several studies have shown that clear lens extraction (CLE) effectively lowers IOP in angle-closure. The use of CLE as a primary treatment option has been tested against LPI in the EAGLE study, a large RCT that enroled people with angle-closure and an IOP > 30 mmHg, and those with angle-closure glaucoma. The trial showed CLE to be superior to PI both for IOP control and patient reported quality of life. On these grounds, CLE should be considered for first-line treatment of more advanced angle-closure disease.

Purpose: To describe the results of darkroom prone provocative testing (DRPPT) in primary angle closure suspects (PACS) and to compare the findings to controls with open angles., Methods: 889 subjects with PACS in the Zhongshan Angle Closure Prevention Trial (a randomised controlled trial to compare prophylactic laser iridotomy to no treatment in PACS) and 89 with open angles in the 5-year follow-up of Liwan Eye Study were placed in a darkroom face down for 15 min. Intraocular pressure (IOP) was measured immediately before and after DRPPT., Results: PACS participants were of similar age than controls (59.3 vs 60.5), more often female (82.9% vs 58.4%) and had lower IOP (14.3 vs 15.2 mm Hg). The average IOP increases after DRPPT was 4.3±3 mm Hg in PACS and 5.2±2.8 in controls (p<0.05). 20.5% of controls and 13.9 % of those with PACS developed an IOP spike ≥8 mm Hg after DRPPT (p<0.05). Among PACS, 15.8 % of those with all four quadrants closed had an IOP elevation of ≥ 8 mm Hg as opposed to 10.0%-12.4 % with two or three closed quadrants (p<0.05). DRPPT failed to predict who would reach a clinical trial endpoint over 6-year follow-up of those with PACS., Conclusions: A modified DRPPT failed to separate PACS from those with open angle. Although the test resulted in greater IOP elevation among those PACS participants with all four quadrants closed than in those with two or three closed quadrants, it did not offer any insight into the risk of developing acute or chronic angle closure disease over 6-year follow-up., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Primary angle-closure glaucoma affects 20 million people worldwide. People classified as primary angle closure suspects have a higher but poorly quantified risk of developing glaucoma. We aimed to assess efficacy and safety of laser peripheral iridotomy prophylaxis against primary angle-closure glaucoma in Chinese people classified as primary angle closure suspects., Methods: In this randomised controlled trial, bilateral primary angle closure suspects aged 50-70 years were enrolled at the Zhongshan Ophthalmic Center, a tertiary specialised hospital in Guangzhou, China. Eligible patients received laser peripheral iridotomy in one randomly selected eye, with the other remaining untreated. The primary outcome was incident primary angle closure disease as a composite endpoint of elevation of intraocular pressure, peripheral anterior synechiae, or acute angle-closure during 72 months of follow-up in an intention-to-treat analysis between treated eyes and contralateral controls. This trial is registered with the ISRCTN registry, number ISRCTN45213099., Findings: Of 11 991 screened individuals, 889 individuals were randomly assigned from June 19, 2008 (889 treated and 889 untreated eyes). Incidence of the primary outcome was 4·19 per 1000 eye-years in treated eyes compared with 7·97 per 1000 eye-years in untreated eyes (hazard ratio 0·53; 95% CI 0·30-0·92; p=0·024). A primary outcome event occurred in 19 treated eyes and 36 untreated eyes with a statistically significant difference using pair-wise analysis (p=0·0041). No serious adverse events were observed during follow-up., Interpretation: Incidence of angle-closure disease was very low among individuals classified as primary angle closure suspects identified through community-based screening. Laser peripheral iridotomy had a modest, albeit significant, prophylactic effect. In view of the low incidence rate of outcomes that have no immediate threat to vision, the benefit of prophylactic laser peripheral iridotomy is limited; therefore, widespread prophylactic laser peripheral iridotomy for primary angle-closure suspects is not recommended., Funding: Fight for Sight, the Sun Yat-Sen University 5010 Project Fund, Moorfields Eye Charity, and the National Natural Science Foundation of China., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: To determine the 10-year incidence of all forms of primary angle closure (PAC) in phakic eyes and its risk factors in an urban Chinese population aged 50 years and older., Methods: Survivors of 1405 baseline participants were invited to attend the 10-year follow-up visit in the Liwan Eye Study. Participants with established baseline angle closure, including primary angle closure suspects (PACS), PAC and primary angle closure glaucoma (PACG), or those who underwent bilateral cataract surgery during the 10-year period, as well as those who did not tolerate gonioscopic examinations, were excluded from this analysis. Incident PAC was present when those with open angles at baseline developed angle closure in any form in either eye during the 10-year period., Results: Among 791 participants who returned during the 10-year follow-up visit, 620 (78.4%) provided data on PAC incidence. The 10-year cumulative incidence of any forms of PAC was 20.5% (127/620, 95% CI 17.4% to 24.9%), including 16.9%, 2.4% and 1.1% with incident PACS, PAC and PACG in either eye, respectively. In multiple logistic regression, significant risk factors for incident angle closure were greater baseline lens thickness (OR=1.82 per mm, p=0.003), shallower anterior chamber depth (OR=3.18 per mm decreased, p=0.010) and narrower angle width (OR=1.63 per decreased angle width, p<0.0001)., Conclusions: Approximately one in five people aged 50 years and older developed some form of angle closure over a 10-year period. Small ocular dimensions and hyperopia at baseline were associated with the development of angle closure., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To describe the surgical technique and refractive outcomes following clear lens extraction (CLE) in the Effectiveness, in Angle-closure Glaucoma, of Lens Extraction trial., Methods: Review of prospectively collected data from a multicentre, randomised controlled trial comparing CLE and laser peripheral iridotomy. Eligible participants were ≥50 years old and newly diagnosed with (1) primary angle closure (PAC) with intraocular pressure above 30 mm Hg or (2) PAC glaucoma. We report the postoperative corrected distance visual acuity (CDVA) and refractive outcomes at 12 and 36 months postoperatively for those who underwent CLE., Results: Of the 419 participants, 208 were randomised to CLE. Mean baseline CDVA was 77.9 (SD 12.4) letters and did not change significantly at 36 months when mean CDVA was 79.9 (SD 10.9) letters. Mean preoperative spherical equivalents were +1.7 (SD 2.3) and +0.08 (SD 0.95) diopters (D) at 36 months. Fifty-nine per cent and 85% eyes were within ±0.5D and ±1.0D of predicted refraction, respectively, at 36 months., Conclusions: Mean CDVA in patients undergoing CLE for angle-closure glaucoma appeared stable over the 3-year study period. Refractive error was significantly reduced with surgery but refractive predictability was suboptimal., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To determine the incidence and baseline clinical and anterior segment optical coherence tomography (AS-OCT) predictors associated with residual angle closure as assessed by gonioscopy 1 year after laser peripheral iridotomy (LPI) in primary angle closure suspects (PACS)., Design: Subanalysis of randomized controlled trial data., Methods: AS-OCT images from 181 PACS subjects ≥50 years of age were analyzed using customized software before and 1 year after LPI. Other parameters assessed were intraocular pressure (IOP) and axial length (Axl). Residual angle closure was defined as the inability to see the posterior trabecular meshwork for at least 2 quadrants on gonioscopy after LPI. Multivariate regression analysis determined the baseline predictors of residual angle closure 1 year after LPI., Results: The mean age of participants was 62.4 (standard deviation 9.9) years. The majority were female (137, 75.7%) and Chinese (174, 96.1%). At 1 year post LPI, 148 (81.8%) subjects had gonioscopic residual angle closure. Univariate analysis showed that baseline Axl, anterior chamber area, anterior chamber volume, angle opening distance at 750 μm from the scleral spur, and angle recess area were smaller while baseline lens vault and iris curvature were larger in residual angle closure subjects (all P < .05). Multivariate analysis revealed that baseline iris volume (B = -0.08, P = .035) and baseline IOP (B = 0.23, P = .032) were predictors for residual angle closure., Conclusions: One year after LPI, >80% of PACS had gonioscopic residual angle closure. Greater baseline iris volume and higher IOP at baseline are independent risk factors for residual gonioscopic angle closure., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Primary angle-closure glaucoma is a leading cause of irreversible blindness worldwide. In early-stage disease, intraocular pressure is raised without visual loss. Because the crystalline lens has a major mechanistic role, lens extraction might be a useful initial treatment., Methods: From Jan 8, 2009, to Dec 28, 2011, we enrolled patients from 30 hospital eye services in five countries. Randomisation was done by a web-based application. Patients were assigned to undergo clear-lens extraction or receive standard care with laser peripheral iridotomy and topical medical treatment. Eligible patients were aged 50 years or older, did not have cataracts, and had newly diagnosed primary angle closure with intraocular pressure 30 mm Hg or greater or primary angle-closure glaucoma. The co-primary endpoints were patient-reported health status, intraocular pressure, and incremental cost-effectiveness ratio per quality-adjusted life-year gained 36 months after treatment. Analysis was by intention to treat. This study is registered, number ISRCTN44464607., Findings: Of 419 participants enrolled, 155 had primary angle closure and 263 primary angle-closure glaucoma. 208 were assigned to clear-lens extraction and 211 to standard care, of whom 351 (84%) had complete data on health status and 366 (87%) on intraocular pressure. The mean health status score (0·87 [SD 0·12]), assessed with the European Quality of Life-5 Dimensions questionnaire, was 0·052 higher (95% CI 0·015-0·088, p=0·005) and mean intraocular pressure (16·6 [SD 3·5] mm Hg) 1·18 mm Hg lower (95% CI -1·99 to -0·38, p=0·004) after clear-lens extraction than after standard care. The incremental cost-effectiveness ratio was £14 284 for initial lens extraction versus standard care. Irreversible loss of vision occurred in one participant who underwent clear-lens extraction and three who received standard care. No patients had serious adverse events., Interpretation: Clear-lens extraction showed greater efficacy and was more cost-effective than laser peripheral iridotomy, and should be considered as an option for first-line treatment., Funding: Medical Research Council., (Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.

Objective: To determine longitudinal changes in angle configuration in the eyes of primary angle-closure suspects (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 coherence 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 under static 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-OCT images., Results: No significant difference was found in baseline measures of angle configuration between treated and untreated eyes. At 2 weeks after LPI, the drainage angle on gonioscopy widened from a mean of 13.5° at baseline to a mean of 25.7° in treated eyes, which was also confirmed by significant increases in all AS-OCT angle width measures (P<0.001 for all variables). Between 2 weeks and 18 months after LPI, a significant decrease in angle width was observed over time in treated eyes (P<0.001 for all variables), although the change over the first 5.5 months was not statistically significant for angle width measured under gonioscopy (P = 0.18), AOD250 (P = 0.167) and ARA (P = 0.83). In untreated eyes, angle width consistently decreased across all follow-up visits after LPI, with a more rapid longitudinal decrease compared with treated eyes (P values for all variables ≤0.003). The annual rate of change in angle width was equivalent to 1.2°/year (95% confidence interval [CI], 0.8-1.6) in treated eyes and 1.6°/year (95% CI, 1.3-2.0) in untreated eyes (P<0.001)., Conclusions: Angle width of treated eyes increased markedly after LPI, remained stable for 6 months, and then decreased significantly by 18 months after LPI. Untreated eyes experienced a more consistent and rapid decrease in angle width over the same time period., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the associations between narrow angle and adult anthropometry., Methods: Chinese adults aged 50 years and older were recruited from a population-based survey in the Liwan District of Guangzhou, China. Narrow angle was defined as the posterior trabecular meshwork not visible under static gonioscopy in at least three quadrants (i.e. a circumference of at least 270°). Logistic regression models were used to examine the associations between narrow angle and anthropomorphic measures (height, weight and body mass index, BMI)., Results: Among the 912 participants, lower weight, shorter height, and lower BMI were significantly associated with narrower angle width (tests for trend: mean angle width in degrees vs weight p < 0.001; vs height p < 0.001; vs BMI p = 0.012). In univariate analyses, shorter height, lower weight and lower BMI were all significantly associated with greater odds of narrow angle. The crude association between height and narrow angle was largely attributable to a stronger association with age and sex. Lower BMI and weight remained significantly associated with narrow angle after adjustment for height, age, sex, axial ocular biometric measures and education. In analyses stratified by sex, the association between BMI and narrow angle was only observed in women., Conclusion: Lower BMI and weight were associated with significantly greater odds of narrow angle after adjusting for age, education, axial ocular biometric measures and height. The odds of narrow angle increased 7% per 1 unit decrease in BMI. This association was most evident in women.

Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size =  -0.045 mm, P = 8.17 × 10(-9)). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45 × 10(-9); 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.

Background/aims: To investigate longitudinal changes in anterior chamber depth (ACD) and axial length (AXL) over 5 years after trabeculectomy surgery in Asian patients with primary glaucoma, and to identify factors associated with these changes., Methods: In this prospective cohort study, phakic subjects with primary glaucoma who underwent trabeculectomy had ACD and AXL measured over 5 years. The effect of intraocular pressure (IOP) on ACD and AXL was determined. Subjects were divided into two groups (high or low fluctuation of ACD/AXL) and factors were compared to determine if there were factors associated with greater fluctuation., Results: 122 subjects were analysed. The majority of subjects were male (75.4%) and Chinese (77%). ACD and AXL were shallower/shorter compared with baseline at all postoperative visits, with a mean decrease of 0.11 mm (95% CI 0.07 to 0.15 mm, p<0.01) and 0.16 mm (95%CI 0.11 to 0.20 mm, p<0.01), respectively. Patients with primary open angle glaucoma (POAG) had higher odds of fluctuations in longitudinal measurements of ACD (OR=8.74, p<0.01) and AXL (OR=5.60, p<0.01) compared with patients with primary angle closure glaucoma. For every 1 mm Hg decrease in IOP, ACD and AXL decreased by 0.02 mm (p<0.01) and 0.01 mm (p=0.03), respectively, for POAG patients with emmetropia or mild myopia., Conclusions: Trabeculectomy resulted in a decrease in both ACD and AXL, and these changes were persistent over a period of 5 years.

Aims: To investigate if the single nucleotide polymorphisms rs3753841, rs1015213 and rs11024102, recently implicated in the development of acute primary angle closure or primary angle closure glaucoma, are associated with ocular biometric characteristics of British adults in the European Prospective Investigation of Cancer-Norfolk eye study., Methods: Genotyping data on rs1015213 (between PCMTD1 and ST18), rs11024102 (at PLEKHA7) and rs3753841 (at COL11A1) were available on 3268 participants. Direct genotypic data was available for rs1015213 and rs3753841. Data was imputed for rs11024102. Ocular biometric data was available on 1137 participants who attended the third European Prospective Investigation of Cancer health examination and 988 (87%) of these participants had no previous cataract surgery either eye. Axial length (AL), anterior chamber depth (ACD) and corneal keratometry were measured by using the Zeiss IOLMaster., Results: Presence of at least one A allele (AG or AA genotype) for rs1015213 was associated with a shallower ACD (-0.07 mm, 95% CI -0.01 to -0.14 mm, p=0.028) after adjusting for age and sex (both p≤0.001). There was no association with AL or corneal keratometry for rs1015213 genotypes. AL, ACD and keratometry were not associated with rs3753841 or rs11024102 genotypes including after adjusting for age and sex., Conclusions: This study suggests that primary angle closure glaucoma susceptibility at the PCMTD1-ST18 locus may be partly explained by an association between rs1015213 and ACD in European populations. This effect is equivalent to almost 20% of the SD of the mean ACD of phakic individuals in this cohort. We were not able to identify any association between rs3753841 or rs11024102 and ocular biometry.

Objective: To report the 8-year outcomes of Asian subjects who underwent trabeculectomy augmented by intraoperative 5-fluorouracil (5-FU) or placebo., Design: Retrospective review of a randomized controlled trial., Participants: Subjects with primary open-angle or angle-closure glaucoma., Methods: Study subjects were prospectively followed up for 3 years. After the last subject recruited had completed 8 years of follow-up, the charts of all subjects were reviewed to capture data from the year 3 visit onward. Kaplan-Meier survival function with Cox regression was performed to identify risk factors associated with trabeculectomy failure at 8 years., Main Outcome Measures: The primary outcome was trabeculectomy failure defined as intraocular pressure (IOP) >21 or <6 mmHg on 2 consecutive occasions after the first 6 weeks after surgery, repeat glaucoma surgery, or loss of light perception. Further end points were defined at IOP levels >17 and >14 mmHg. Secondary outcomes included IOP at 8 years and number of glaucoma medications. Complete success was defined using IOP end points ≤ 21, ≤ 17, or ≤ 14 mmHg at 8 years without medications., Results: Of the 243 enrolled subjects, 170 (70.0%) completed 8 years follow-up, 86 in the 5-FU and 84 in the placebo group. There was no significant difference in failure rates at 8 years for the failure definitions of IOP >21 mmHg (11.6% of the 5-FU group vs. 16.7% of the placebo group; P = 1.00), IOP >17 mmHg (23.3% of the 5-FU group vs. 31% of the placebo group; P = 0.78), and IOP >14 mmHg (46.5% of the 5-FU group vs. 58.3% of the placebo group; P = 0.37). Mean IOP at 8 years was 13.7 mmHg in the 5-FU versus 14.4 mmHg in the placebo group (P = 0.24). Mean number of medications was 0.65 drops in the 5-FU versus 0.93 drops in the placebo group (P = 0.06). Complete success with IOP ≤ 21 mmHg at 8 years was achieved in 48 subjects (55.8%) in the 5-FU and 33 subjects (39.3%) in the placebo group (P = 0.09). Absence of bleb microcysts at 1 year, preoperative IOP, and number of bleb needlings performed within the first year were significantly associated with failure., Conclusions: There was no significant difference in IOP between the 5-FU and the placebo group at 8 years., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the effect of prophylactic laser peripheral iridotomy (LPI) on corneal endothelial cell density (ECD) and morphology in primary angle closure suspects (PACS) over 3 years., Methods: In this prospective cohort study, subjects underwent LPI in one eye, while the fellow eye was untreated. Specular microscopy was performed at baseline and after 1 and 3 years. Central corneal ECD and morphology of both eyes were assessed using non-contact specular microscopy (Konan SP-9000LC, Konan Inc, Hyogo, Japan)., Results: 230 subjects completed 3-year follow-up. The mean age was 62.5 ± 8.0 years, and the majority of subjects were Chinese (92.3%) and women (75.4%). In eyes that underwent LPI, ECD was significantly lower at year 1 (2462.3, 95% CI 2414.5 to 2510.0, p<0.0001) and year 3 (2510.6, 95% CI 2462.1 to 2559.2, p=0.0006) compared with baseline (2609.1, 95% CI 2551.4 to 2666.7). There was also a significant decrease in ECD in fellow untreated eyes from baseline to year 1 (p<0.0001) and year 3 (p=0.01). The decrease in ECD at 3 years compared with the baseline in treated and untreated eyes was similar (2.1% vs 0.9%, p=0.20)., Conclusions: In PACS eyes, there was decrease in ECD in LPI-treated and control eyes over 3 years, with no significant difference between groups.

Purpose: To measure the dimensions of aqueous outflow structures and to investigate associations with intraocular pressure (IOP) and ocular biometry parameters in an older British population., Method: Fifty-two participants from the European Prospective Investigation of Cancer-Norfolk eye study underwent imaging using the Heidelberg Spectralis optical coherence tomographer with an anterior segment module. Pseudophakic participants and those known or suspected to have glaucoma were excluded, leaving 46 participants for analysis. Schwalbe's line (SL), scleral spur (SS), Schlemm's canal (SC) diameter and the trabecular meshwork cross-sectional area (TM cross-sectional area (CSA)) were identified and traced using ImageJ software. IOP was measured using the Ocular Response Analyser. Ocular biometry was measured by partial coherence interferometry., Results: The mean (SD) subject age was 65.7 years (5.6). The SL and SS were identifiable in all nasal and temporal scans. The mean SL-SS distance was 800 μm (104) nasally and 808 μm (102) temporally. Repeatability of SS-SL, SS-SC, SC and TM CSA was good to excellent, and reproducibility fair to good. Nasal SL-SS distance was inversely associated with anterior chamber depth (ACD) (p=0.007, -116 μm per mm ACD, R(2)=0.18). Multiple linear regression showed nasal TM CSA was significantly associated with age and IOP (age: p=0.025, 0.007 mm(2) per decade of age; IOP: p=0.029, -0.0012 mm(2) per mm Hg, R(2)=0.23)., Conclusions: Aqueous outflow structures can be measured by optical coherence tomography, and their dimensions vary significantly with ocular biometric characteristics and IOP. Further investigation is required to determine associations between outflow structure sizes in different populations and pathologies, including ocular hypertension and glaucoma.

Purpose: To examine the clinical outcomes of cataract extraction in eyes with primary angle closure (PAC) and coexisting cataract., Patients and Methods: Retrospective study of surgical outcomes after phacoemulsification and intraocular lens implantation in 55 eyes of 39 patients with PAC or occludable angles and visually symptomatic cataract. Approximately, 61.8% of eyes had received a peripheral iridotomy and 65% had evidence of glaucomatous optic neuropathy (GON)., Results: At 7.2 months after cataract extraction, a statistically significant reduction in intraocular pressure (IOP) was observed in all eyes with PAC (median 3 mm Hg, P=<0.0001). The reduction in IOP was significantly greater in eyes with a higher preoperative IOP (P=<0.0001). On average, one less glaucoma medication was in use postoperatively (P=0.01). Eyes with >180 degrees of peripheral anterior synechiae (PAS) preoperatively achieved a significantly greater reduction in IOP postoperatively compared with those with less PAS (7.5 vs. 4.4 mm Hg, P=0.03). The observed reduction in IOP in eyes with PAC and GON was significantly greater compared with those without GON (5.6 vs. 2.5 mm Hg, P=0.01). Visual acuity was significantly improved after cataract extraction by a mean of -0.23 LogMAR units (P=0.0001)., Conclusions: Contrary to earlier expectations, the observed reduction in postoperative IOP in eyes with PAC was significantly greater in the presence of a higher preoperative IOP, a larger number of glaucoma medication, narrower iridotrabecular angle width, and greater extent of PAS formation and in eyes with evidence of GON. Lens extraction seems to have a beneficial effect on IOP control in PAC, and is especially efficacious in more advanced cases.

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR)=1.22; P=5.33×10(-12)), rs3753841 in COL11A1 (per-allele OR=1.20; P=9.22×10(-10)) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR=1.50; P=3.29×10(-9)). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG.

Aim: To estimate the prevalence of primary angle closure glaucoma (PACG) in European derived populations., Method: Systematic review and modelling of PACG prevalence data from population studies. PACG was defined according to the ISGEO definition requiring structural and/or functional evidence of glaucomatous optic neuropathy. Prevalence estimates were applied to the 2010 United Nations projected population figures to estimate case numbers., Results: The prevalence of PACG in those 40 years or more is 0.4% (95% CI 0.3% to 0.5%). Age-specific prevalence values are 0.02% (CI 0.00 to 0.08) for those 40-49 years, 0.60% (0.27 to 1.00) for those 50-59 years, 0.20% (0.06 to 0.42) for those 60-69 years and 0.94% (0.63 to 1.35) for those 70 years and older. Three-quarters of all cases occur in female subjects (3.25 female to 1 male; CI 1.76 to 5.94)., Conclusion: This analysis provides a current evidence-based estimate of PACG prevalence in European derived populations and suggests there are 130,000 people in the UK, 1.60 million people in Europe and 581,000 people in the USA with PACG today. Accounting for ageing population structures, cases are predicted to increase by 19% in the UK, 9% in Europe and 18% in the USA within the next decade. PACG is more common than previously thought, and all primary glaucoma cases should be considered to be PACG until the anterior chamber angle is shown to be open on gonioscopy.

Purpose: Novel anterior segment optical coherence tomography (ASOCT) parameters associated with angle closure include anterior chamber area (ACA), anterior chamber volume (ACV), anterior chamber width (ACW), lens vault (LV), iris thickness (IT), iris area (I-area), and iris curvature (I-curv). We aimed to investigate changes in these parameters after laser peripheral iridotomy (LPI) in a cohort of primary angle-closure suspects (PACS)., Design: Prospective observational study., Participants and Controls: A total of 176 PACS aged ≥ 50 years who underwent LPI in 1 eye., Methods: We analyzed ASOCT images (Visante, Carl Zeiss Meditec, Dublin, CA) from all subjects using customized software before and 1 week after LPI. Multivariate linear regression analysis was performed for predictors of percentage change in mean angle opening distance (AOD750)., Main Outcome Measures: Change in ASOCT parameters after LPI., Results: The mean age of participants was 63 ± 7.3 years. The majority of subjects were Chinese (95.5%) and women (76.7%). Mean angle width (modified Shaffer grade) changed from 0.68 ± 0.54 at baseline to 1.76±0.69 after LPI (P<0.001) with a corresponding increase in mean AOD500 (0.12 vs. 0.19 mm, P<0.001), trabecular iris surface area (TISA500, 0.06 vs. 0.08 mm(2), P<0.001), and angle recess area (ARA, 0.13 vs. 0.17 mm(2), P<0.001). Mean ACA (15.0 vs. 16.0 mm(2), P<0.001) and ACV (91.6 vs. 103.0 mm(3), P<0.001) increased significantly after LPI, but there was no change in ACW, anterior chamber depth (ACD), or LV. Mean I-curv was reduced (0.375 vs. 0.18 mm, P<0.001) after LPI, but there was no significant change in IT or I-area. After multivariate analysis, mean LV (β = 0.286, P = 0.001), mean IT at 2000 μm (IT2000, β = 0.172, P = 0.034), and intraocular pressure (β = 0.159, P = 0.042) at baseline were found to be associated with ΔAOD750., Conclusions: This study confirms that LPI results in a significant increase in the angle width in PACS. The ACA and ACV increased after LPI, but there was no change in ACD, ACW, LV, IT, or I-area. The increase in ACA/ACV was mainly due to decreased I-curv after LPI., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the impact of laser peripheral iridotomy (LPI) on forward-scatter of light and subjective visual symptoms and to identify LPI parameters influencing these phenomena., Design: Cohort study derived from a randomized trial, using an external control group., Participants: Chinese subjects initially aged 50 or older and 70 years or younger with bilateral narrow angles undergoing LPI in 1 eye selected at random, and age- and gender-matched controls., Methods: Eighteen months after laser, LPI-treated subjects underwent digital iris photography and photogrammetry to characterize the size and location of the LPI, Lens Opacity Classification System III cataract grading, and measurement of retinal straylight (C-Quant; OCULUS, Wetzlar, Germany) in the treated and untreated eyes and completed a visual symptoms questionnaire. Controls answered the questionnaire and underwent straylight measurement and (in a random one-sixth sample) cataract grading., Main Outcome Measures: Retinal straylight levels and subjective visual symptoms., Results: Among 230 LPI-treated subjects (121 [58.8%] with LPI totally covered by the lid, 43 [19.8%] with LPI partly covered by the lid, 53 [24.4%] with LPI uncovered by the lid), 217 (94.3%) completed all testing, as did 250 (93.3%) of 268 controls. Age, gender, and prevalence of visual symptoms did not differ between treated subjects and controls, although nuclear (P<0.01) and cortical (P = 0.03) cataract were less common among controls. Neither presenting visual acuity nor straylight score differed between the treated and untreated eyes among all treated persons, nor among those (n = 96) with LPI partially or totally uncovered. Prevalence of subjective glare did not differ significantly between participants with totally covered LPI (6.61%; 95% confidence interval [CI], 3.39%-12.5%), partially covered LPI (11.6%; 95% CI, 5.07%-24.5%), or totally uncovered LPI (9.43%; 95% CI, 4.10%-10.3%). In regression models, only worse cortical cataract grade (P = 0.01) was associated significantly with straylight score, and no predictors were associated with subjective glare. None of the LPI size or location parameters were associated with straylight or subjective symptoms., Conclusions: These results suggests that LPI is safe regarding measures of straylight and visual symptoms. This randomized design provides strong evidence that treatment programs for narrow angles would be unlikely to result in important medium-term visual disability., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

A 34-year-old Caucasian female with advanced primary angle closure glaucoma developed acute angle closure following administration of g.pilocarpine 2% given as preparation for laser peripheral iridotomies. Subsequent investigations supported an underlying diagnosis of spherophakia with no systemic associations. She required peripheral iridotomies, bilateral clear lens extractions and left cyclodiode laser to control her intraocular pressures. This case highlights the situations when pilocarpine should be given with caution and also the increasing role of phacoemulsification as an alternative to filtration surgery in primary angle closure glaucoma management.

Primary angle-closure glaucoma (PACG) frequently leads to severe vision loss. Prevalence among older Asian populations is high and given global demographics, the number of persons with PACG will increase dramatically in the coming decades. Improvements in imaging of the anterior segment will help us to identify more of those with angle closure, and important clinical trials that are currently underway will provide important evidence to support screening and treatment approaches for PACG. In this manuscript, we intend to review the existing evidences, to introduce some important on-going studies on PACG and to share the experience and viewpoints of the authors., (© 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.)

Objective: To evaluate the risk of primary acute angle closure (AAC), changes in intraocular pressure (IOP), and associated risk factors after pupil dilation in Asian subjects with narrow angles (primary angle-closure suspects [PACS])., Design: Prospective clinical study., Participants: A total of 471 subjects aged more than 50 years with narrow angles in Singapore., Methods: This study was part of a prospective trial of PACS. Subjects underwent a detailed ophthalmic evaluation including gonioscopy, biometry, pachymetry, and ultrasound biomicroscopy. All subjects underwent pupil dilation with 1% tropicamide eye drops at the baseline visit, before any laser or medical intervention. Intraocular pressure was measured using Goldmann applanation tonometry by the same observer before and 1 hour after pupil dilation. A dose of oral acetazolamide was given before the patient left the clinic., Main Outcome Measures: Intraocular pressure before and after dilation, and an AAC event., Results: The mean age of the 471 subjects was 63.0 ± 6.9 years (mean ± standard deviation); 75.4% were women, and 92.8% were Chinese. Of the 471 participants, 3 (0.64%; 95% confidence interval [CI], 0.13-1.85) developed AAC within 6 hours of dilation despite pretreatment with oral acetazolamide. Twenty-two subjects (4.67%; 95% CI, 2.95-6.99) showed a postdilation increase in IOP of ≥ 5 mmHg in either eye, 6 subjects (1.27%; 95% CI, 0.47-2.75) had an IOP increase of ≥ 8 mmHg in either eye, and 4 subjects (0.85%; 95% CI, 0.23-2.16) had a postdilation IOP of >25 mmHg in either eye. Narrower gonioscopic angle width, that is, having a lower mean gonioscopic modified Shaffer grading (coefficient β -0.51; standard error 0.19; P=0.01), and predilation IOP level (coefficient β -0.17; standard error 0.04; P < 0.001) were significant risk factors for IOP increase after dilation in multivariate linear regression analysis., Conclusions: The risk of AAC among Asian subjects with narrow angles was low after pupillary dilation with tropicamide and oral acetazolamide prophylaxis. The presence of narrower angle width by gonioscopy was the only clinical parameter identified for a significant IOP increase after pupil dilation., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Aims: To compare iridotomy outcomes in dark irides by 1064 nm pulsed Nd:YAG laser with and without 532 nm continuous-wave Nd:YAG (frequency-doubled) green laser pretreatment., Methods: 30 patients with occludable anterior chamber angles underwent bilateral standard pulsed 1064 nm Nd:YAG laser iridotomy with one eye randomly assigned to sequential pretreatment with 532 nm continuous-wave Nd:YAG laser. Outcome measures were iridotomy patency and complications including haemorrhage and elevated intraocular pressure (IOP)., Results: Median pulsed YAG power in the standard treatment group was 37.5 mJ (IQR 25-77) and 22.5 mJ (IQR 14-32) in the sequential treatment group (p=0.0079). Iris haemorrhage occurred in 43% of the standard treatment group and 13% of the sequential treatment group (p=0.0126). All iridotomies were patent at the end of the procedure in the sequential treatment group, while 2/30 in the standard treatment group were abandoned due to significant haemorrhage. Mean IOP at 1 h was significantly lower than pre-laser values in both groups (with magnitude of reduction significantly more in the sequential treatment group). There was no significant change in IOP at 1 week. All iridotomies were patent at last follow-up of median 38.5 months (IQR 32.0-42.3)., Conclusions: This study provides evidence that iridotomy with pretreatment using a continuous-wave Nd:YAG laser is safer and more effective than pulsed Nd:YAG-only laser iridotomy for dark irides and should be considered as the preferred technique.

Purpose: To determine the immediate changes in intraocular pressure (IOP) after laser peripheral iridotomy in primary angle-closure suspects., Design: Prospective, randomized controlled trial (split-body design)., Participants: Seven hundred thirty-four Chinese people 50 to 70 years of age., Methods: Primary angle-closure suspects underwent iridotomy using a neodymium:yttrium-aluminum-garnet laser in 1 randomly selected eye, with the fellow eye serving as a control. Intraocular pressure was measured using Goldmann applanation tonometry before treatment and 1 hour and 2 weeks after treatment. Total energy used and complications were recorded. Risk factors for IOP rise after laser peripheral iridotomy were investigated., Main Outcome Measures: Intraocular pressure., Results: The proportion of treated eyes with an IOP spike (an elevation of ≥8 mmHg more than baseline) at 1 hour and 2 weeks after treatment was 9.8% (95% confidence interval [CI], 7.7-12.0) and 0.82% (95% CI, 0.2-1.5), respectively. Only 4 (0.54%) of 734 eyes (95% CI, 0.01-1.08) had an immediate posttreatment IOP of 30 mmHg or more and needed medical intervention. The average IOP 1 hour after treatment was 17.5±4.7 mmHg in the treated eyes, as compared with 15.2±2.6 mmHg in controls. At 2 weeks after treatment, these values were 15.6±3.4 mmHg in treated eyes and 15.1±2.7 mmHg in controls (P<0.001). No significant difference was detected in the baseline IOP of the treated and untreated eyes. Logistic regression showed that the incidence of IOP spike was associated with greater laser energy used and shallower central anterior chamber., Conclusions: Laser peripheral iridotomy in primary angle-closure suspects resulted in significant IOP rise in 9.8% and 0.82% of cases at 1 hour and 2 weeks, respectively. Eyes in which more laser energy and a higher number of laser pulses were used and those with shallower central anterior chambers were at increased risk for IOP spikes at 1 hour after laser peripheral iridotomy., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether the timing of cataract surgery after trabeculectomy has an effect on trabeculectomy function in terms of intraocular pressure control., Methods: This was a cohort study nested within a randomized clinical trial. There were 235 participants with glaucoma who had a single previous trabeculectomy augmented with either intraoperative 5-fluorouracil or placebo. Cataract surgery with intraocular lens implantation was performed on participants judged to have significant lens opacity. Cox regression was performed to evaluate the effect of time between trabeculectomy and cataract surgery on the time to trabeculectomy failure, after adjusting for other relevant risk factors. The main outcome measure was time to failure of trabeculectomy, defined as an intraocular pressure of greater than 21 mm Hg., Results: Of the 235 participants, 124 (52.7%) underwent subsequent cataract surgery. The median time from trabeculectomy to cataract surgery for these patients was 21.7 months (range, 4.6-81.9 months). The median follow-up period was 60 months (range, 28-84 months) for the cataract surgery group and 48 months (range, 12-84 months) for the non-cataract surgery group. Cox regression showed that the time from trabeculectomy to cataract surgery was significantly associated with time to trabeculectomy failure (hazard ratio, 1.73 [95% CI, 1.05-2.85]; P = .03). The adjusted declining hazard ratios for risk of subsequent trabeculectomy failure when cataract surgery was performed 6 months, 1 year, and 2 years after trabeculectomy were 3.00 (95% CI, 1.11-8.14), 1.73 (95% CI, 1.05-2.85), and 1.32 (95% CI, 1.02-1.69), respectively., Conclusions: Cataract surgery after trabeculectomy increases the risk of trabeculectomy failure, and this risk is increased if the time between trabeculectomy and cataract surgery is shorter.

Purpose: To examine the association between central corneal thickness (CCT) and glaucoma., Methods: This was a nested case-control study using 1090 subjects from an eye disease population survey in Singapore and 243 participants from a hospital glaucoma surgery clinical trial in Singapore., Results: Mean CCT in 938 community subjects was 539 μm ± 32 μm, and in 12 community subjects with primary open angle glaucoma (POAG) the mean CCT was 545 μm ± 38 μm. In the hospital cohort, mean CCT was 552 μm ± 38 μm in 138 patients with POAG and 551 μm ± 33 μm in 105 patients with primary angle closure glaucoma (PACG). No individuals had undergone previous intraocular surgery or had other significant ocular pathology. Regression models showed POAG diagnosis was not associated with CCT (P = 0.42) or age (P = 0.062) in community subjects but was associated with IOP (P = 0.005). Similar analyses for hospital cases showed CCT to be significantly higher in both POAG and PACG (both P = 0.001), but this became nonsignificant after controlling for IOP and age (P = 0.26, POAG; P = 0.08, PACG). Both age (P = 0.043) and IOP (P = 0.001) were highly associated with hospital POAG; only IOP (P = 0.001) was associated with hospital PACG. Further regression analyses for community subjects showed diabetic status and pseudophakia had no significant effect on CCT (P = 0.33 and P = 0.11, respectively)., Conclusions: The authors found no evidence to support the previous observation that thinner corneas may be independently associated with POAG or PACG. Age and IOP are significantly associated with CCT, and this should be taken into account by future studies investigating CCT as an independent risk factor for glaucoma diagnosis.

Purpose: To examine the relationship between education, other risk factors and incident primary angle closure glaucoma (PACG)., Method: Glaucoma was excluded in a group of 4597 Mongolian volunteers in 1999. After 6 years, 1892 traced participants had full ophthalmic examination, dilated disc photographs and agreed to complete a questionnaire on socio-economic status. PACG was diagnosed using both structural and functional evidence from objective grading of paired disc photographs, follow up visual fields and clinical examination. Ophthalmic examination included van Herick grading, Goldmann intraocular pressure (IOP), gonioscopy, lens opacity grading and dilated disc examination. Central anterior chamber depth, lens thickness and axial length were recorded using ultrasound A scan mounted on a slitlamp. Education level was assessed using national census categories., Results: PACG was diagnosed in 29 participants (6 year incidence = 1.53%, 95% confidence interval (CI) = 1.03-2.19%). In univariate analysis, risk factors for incident PACG included presence of refractive error, narrow van Herick grading of ≤15%, narrower average Shaffer grading, higher IOP, larger cup disc ratio and lower levels of education. In multivariate analysis, adjusted for age, sex, Shaffer grading, refractive error and IOP, those with no formal education were approximately 7 times more likely to develop PACG compared to those with >8 years of formal schooling (OR = 7.27, 95% CI = 2.73-19.38)., Conclusions: People with lower levels of education have a higher risk of incident PACG, independent of age, sex, IOP and axial length.

Purpose: To describe the characteristics of the iridocorneal angle using ultrasound biomicroscopy (UBM) in Chinese people classified gonioscopically as having suspected primary angle-closure (PACS) glaucoma., Methods: PACS were defined as not having visible posterior (usually pigmented) trabecular meshwork in two or more quadrants examined by static gonioscopy. The PACS and 1 of 10 those who did not meet this criterion were identified from a population-based survey. Iridotrabecular meshwork contact (ITC) was identified and further classified into low and high, according to standard UBM images. Those with high ITC were further classified according the configuration of ITC: B-type, with contiguous ITC from the base of the angle, and S-type, with ITC localized to the region of Schwalbe's line., Results: ITC was identified in 78.6% of the superior, 40.2% of the nasal, 59.8% of the inferior, and 25.6% of the temporal quadrants in the PACS (n = 117). These proportions were 43.9%, 15.8%, 29.8%, and 14.0% in the controls (n = 57), respectively. About two thirds of the eyes with ITC were classified as high. In those with high ITC, the number with B- and S-type ITC was very similar. The proportions of any high ITCs increased substantially from 15.4% in those with Shaffer angle grade 4 and 45.0% in grade 3, to 71.0% in grade 2, 70.2% in grade 1, and 86.4% in grade 0., Conclusions: More ITC is identified on UBM imaging than by gonioscopy. Careful consideration should be given to the assessment modality regarded as the reference standard in defining anatomic risk factors for glaucomatous visual loss and the need for treatment.