Hon-Tym Wong

Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma

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.

ABCC5, a Gene That Influences the Anterior Chamber Depth, Is Associated with Primary Angle Closure Glaucoma

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.

Iris ischaemic changes and visual outcome after acute primary angle closure.

Background:  Ischaemic changes in the iris occur frequently after an episode of acute primary angle closure (APAC). The aim of this study was to investigate the significance of such changes with regards to visual outcome.

Comparative Efficacy and Tolerability of Topical Prostaglandin Analogues for Primary Open-Angle Glaucoma and Ocular Hypertension

Objective: To systematically review the efficacy and tolerability of 4 prostaglandin analogues (PGAs) as first-line monotherapies for intraocular pressure (IOP) lowering in adult patients with primary open-angle glaucoma or ocular hypertension. Data Sources: A literature search was performed in PubMed (1965-June 2013) and the Cochrane Library (1980-June 2013) using the search terms ocular hypertension, open-angle glaucoma, prostaglandin analogues, bimatoprost, latanoprost, tafluprost, and travoprost. Additional studies were searched from the reference lists of identified publications. Study Selection and Data Extraction: In all, 32 randomized controlled trials comparing between PGAs (bimatoprost 0.03%, latanoprost 0.005%, tafluprost 0.0015%, and travoprost 0.004%) or PGA with timolol were selected. Data Synthesis: A network meta-analysis was conducted. Using timolol as reference, the relative risks (RRs) of achieving treatment success, defined as the proportion of patients achieving at least 30% IOP reduction, with 95% CIs, were as follows: bimatoprost, 1.59 (1.28-1.98); latanoprost, 1.32 (1.00-1.74); travoprost, 1.33 (1.03-1.72); and tafluprost, 1.10 (0.85-1.42). The mean IOP reductions after 1 month were 1.98 (1.50-2.47), 1.01 (0.55-1.46), 1.08 (0.59-1.57), and 0.46 (−0.41 to 1.33) mm Hg, respectively, and the results were sustained at 3 months. Bimatoprost was associated with the highest risk of developing hyperemia, whereas latanoprost had the lowest risk, with RRs (95% CI) of 4.66 (3.49-6.23) and 2.30 (1.76-3.00), respectively. Conclusions: Bimatoprost achieved the highest efficacy in terms of IOP reduction, whereas latanoprost had the most favorable tolerability profile. This review serves to guide selection of the optimal PGA agent for individual patient care in clinical practice.

National survey of ophthalmologists in Singapore for the assessment and management of asymptomatic angle closure.

PurposeApproximately 10% of Chinese people older than 50 years in Singapore have asymptomatic narrow angles [also termed primary angle closure suspects (PACS)]. The aim of this study was to determine the attitudes and practices of ophthalmologists in Singapore regarding the management of these patients. MethodsA nation wide questionnaire-based survey was conducted on all registered, practicing ophthalmologists in Singapore by electronic mail and post. An ophthalmologist was defined as a doctor who had completed at least 3 years of specialist training in ophthalmology and had passed the Masters Degree in Ophthalmology or equivalent examinations. The survey asked the ophthalmologists about the methods and criteria used for the diagnosis of angle closure. It also inquired about the management of PACS and opinions on the effectiveness of prophylactic laser peripheral iridotomy (LPI) in preventing both acute and chronic angle closure. ResultsA total of 126 out of 158 ophthalmologists responded (79.7% response rate). Of the respondents, 84.9% would advise prophylactic LPI for asymptomatic PACS; 84.9% believed that prophylactic LPI would prevent acute angle closure but only 44% thought that it could prevent the development of glaucomatous optic nerve damage. The preferred method of prophylactic LPI was sequential argon-YAG LPI. In assessing patients for angle closure, 85.4% used gonioscopy, 92.9% assessed anterior chamber depth, and 17.5% performed provocative tests. ConclusionsOphthalmologists in Singapore vary in the method of assessment of patients with angle closure. Most believe that prophylactic LPI should be performed for asymptomatic PACS.

Automatic detection of schwalbe's line in the anterior chamber angle of the eye using HD-OCT images

Angle-closure glaucoma is a major cause of blindness in Asia and could be detected by measuring the anterior chamber angle (ACA) using gonioscopy, ultrasound biomicroscopy or anterior segment (AS) optical coherence tomography (OCT). The current software in the VisanteTM OCT system by Zeiss is based on manual labeling of the scleral spur, cornea and iris and is a tedious process for ophthalmologists. Furthermore, the scleral spur can not be identified in about 20% to 30% of OCT images and thus measurements of the ACA are not reliable. However, high definition (HD) OCT has identified a more consistent landmark: Schwalbes line. This paper presents a novel algorithm which automatically detects Schwalbes line in HD-OCT scans. The average deviation between the values detected using our algorithm and those labeled by the ophthalmologist is less than 0.5% and 0.35% in the horizontal and vertical image dimension, respectively. Furthermore, we propose a new measurement to quantify ACA which is defined as Schwalbes line bounded area (SLBA).

Comparison of Slitlamp Optical Coherence Tomography and Scanning Peripheral Anterior Chamber Depth Analyzer to Evaluate Angle Closure in Asian Eyes

OBJECTIVE To evaluate the effectiveness of slitlamp optical coherence tomography (SL-OCT) and Scanning Peripheral Anterior Chamber depth analyzer (SPAC) in detecting angle closure, using gonioscopy as the reference standard. METHODS A total of 153 subjects underwent gonioscopy, SL-OCT, and SPAC. The anterior chamber angle (ACA) was classified as closed on gonioscopy if the posterior trabecular meshwork could not be seen; with SL-OCT, closure was determined by contact between the iris and angle wall anterior to the scleral spur; and with SPAC by a numerical grade of 5 or fewer and/or a categorical grade of suspect or potential. RESULTS A closed ACA was identified in 51 eyes with gonioscopy, 86 eyes with SL-OCT, and 61 eyes with SPAC (gonioscopy vs SL-OCT, P < .001; gonioscopy vs SPAC, P = .10; SL-OCT vs SPAC, P < .001; McNemar test). Of the 51 eyes with a closed ACA on gonioscopy, SL-OCT detected a closed ACA in 43, whereas SPAC identified 41 (P = .79). An open angle in all 4 quadrants was observed in 102 eyes with gonioscopy, but SL-OCT and SPAC identified 43 and 20 of these eyes, respectively, as having angle closure. The overall sensitivity and specificity for SL-OCT were 84% and 58% vs 80% and 80% for SPAC. CONCLUSION Using gonioscopy as the reference, SL-OCT and SPAC showed good sensitivity for detecting eyes at risk of angle closure.