Evaluating the outcome of screening for glaucoma using colour fundus photography-based referral criteria in a teleophthalmology screening programme for diabetic retinopathy.

AIMS: To evaluate the effectiveness of glaucoma screening using glaucoma suspect (GS) referral criteria assessed on colour fundus photographs in Singapore's Integrated Diabetic Retinopathy Programme (SiDRP). METHODS: A case-control study. This study included diabetic subjects who were referred from SiDRP with and without GS between January 2017 and December 2018 and reviewed at Singapore National Eye Centre. The GS referral criteria were based on the presence of a vertical cup-to-disc ratio (VCDR) of ≥0.65 and other GS features. The final glaucoma diagnosis confirmed from electronic medical records was retrospectively matched with GS status. The sensitivity, specificity and positive predictive value (PPV) of the test were evaluated. RESULTS: Of 5023 patients (2625 with GS and 2398 without GS) reviewed for glaucoma, 451 (9.0%, 95% CI 8.2% to 9.8%) were confirmed as glaucoma. The average follow-up time was 21.5±10.2 months. Using our current GS referral criteria, the sensitivity, specificity and PPV were 81.6% (95% CI 77.7% to 85.1%), 50.6% (95% CI 49.2% to 52.1%) and 14.0% (95% CI 13.4% to 14.7%), respectively, resulting in 2257 false positive cases. Increasing the VCDR cut-off for referral to ≥0.80, the specificity increased to 93.9% (95% CI 93.1% to 94.5%) but the sensitivity decreased to 11.3% (95% CI 8.5% to 14.6%), with a PPV of 15.4% (95% CI 12.0% to 19.4%). CONCLUSIONS: Opportunistic screening for glaucoma in a lower VCDR group could result in a high number of unnecessary referrals. If healthcare infrastructures are limited, targeting case findings on a larger VCDR group with high specificity will still be beneficial.

Prospective 12-month outcomes of combined iStent inject implantation and phacoemulsification in Asian eyes with normal tension glaucoma.

BACKGROUND: Glaucoma is the leading cause of irreversible blindness. Normal tension glaucoma (NTG) is a subset of open-angle glaucoma, demonstrating glaucomatous optic nerve damage in the absence of raised intraocular pressure (IOP). NTG is more prevalent in Asian populations. While generally slow-progressing, NTG may be associated with significant central visual field loss. In recent years, minimally invasive glaucoma surgery has been added to the armamentarium of glaucoma surgery. This prospective study aims to evaluate 12-month surgical outcomes of combined iStent inject (Glaukos Corporation, Laguna Hills, CA) implantation and phacoemulsification in Asian eyes with NTG. METHODS: This is a prospective, single-centre case series of 30 eyes followed up until 12 months after surgery. Outcome measures included IOP, number of glaucoma medications, best-corrected visual acuity (BCVA) and intra and postoperative complications. RESULTS: Mean age of subjects was 73.1 ± 6.3 years. Majority were ethnic Chinese (n = 27, 90%). Baseline medicated mean IOP was 13.8 ± 2.4 mmHg and mean number of glaucoma medications was 1.3 ± 0.7. Mean Humphrey visual field mean deviation was - 13.7 ± 7.6. The mean IOP reduction at all timepoints from postoperative month (POM) 3 onwards was statistically significant (all P < 0.05), with mean reduction of 1.2 mmHg (95% CI: 0.1-2.2, P = 0.037) by POM12. There was statistically significant reduction in mean number of medications from postoperative day (POD) 1 onwards (all P < 0.05), with mean decrease of 1.0 medication (95% CI: 0.9-1.1, P < 0.001) by POM12. By POM12, 25 (83.3%) eyes were medication-free. Three (10%) eyes had stent occlusion by iris requiring laser iridoplasty. One eye had gross hyphema which resolved on conservative management before POM1. Mean BCVA improved from the baseline 0.3 ± 0.3 logMAR to 0.1 ± 0.1 logMAR postoperatively (P < 0.001). There were no major adverse or sight-threatening events. No eyes required further glaucoma surgery during the 12-month follow-up period. CONCLUSION: Asian eyes with NTG which underwent combined iStent inject implantation and phacoemulsification demonstrated a significant and sustained reduction in IOP and glaucoma medications, up to 12 months postoperatively.

The Singapore Asymptomatic Narrow Angles Laser Iridotomy Study: Five-Year Results of a Randomized Controlled Trial.

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.

Effects of primary glaucoma on sleep quality and daytime sleepiness of patients residing at an equatorial latitude.

AIM: To investigate the impact of primary glaucoma on sleep quality and daytime sleepiness of patients. METHODS: Prospective cross-sectional study with consecutive sampling in South-East Asian population was performed. Validated questionnaires: the Pittsburg Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were administered prospectively. Subjects with non-glaucomatous optic neuropathy or concomitant retinal pathology were excluded. Glaucoma severity was based on HVF 24-2 perimetry. Binocular single vision was represented based on the better eye. Frequency of and predictive factors for poor sleep quality and excessive daytime sleepiness were compared. RESULTS: A total of 79 primary open angle glaucoma (POAG), 27 primary angle-closure glaucoma (PACG) patients, and 89 controls were recruited. PACG patients had higher median PSQI scores (P=0.004) and poorer sleep quality (P<0.001). Compared to controls, PACG patients were 3.34 times more likely to have poor sleep quality (P=0.008), which remained significant after adjustment for demographics (P=0.016) and predictive variables (P=0.013). PACG patients have poorer sleep quality when visual acuity (VA) was 6/15 or worse (P=0.009). Univariate and multivariate analysis of predictive variables for poor sleep quality and daytime sleepiness did not find statistical significance. CONCLUSION: PACG patients have poorer sleep quality but not daytime sleepiness. This is important in South-East Asian population with heavy disease burden. Evaluations on sleep disturbances can be considered to provide more holistic care.

Evolving Practice Patterns in Singapore's Public Sector Ophthalmology Centers During the COVID-19 Pandemic.

Coronavirus disease 19 (COVID-19) was first reported in Wuhan, China, in December 2019, and has since become a global pandemic. Singapore was one of the first countries outside of China to be affected and reported its first case in January 2020. Strategies that were deployed successfully during the 2003 outbreak of severe acute respiratory syndrome have had to evolve to contain this novel coronavirus. Like the rest of the health care services in Singapore, the practice of ophthalmology has also had to adapt to this rapidly changing crisis. This article discusses the measures put in place by the 3 largest ophthalmology centers in Singapore's public sector in response to COVID-19, and the challenges of providing eye care in the face of stringent infection control directives, staff redeployments and "social distancing." The recently imposed "circuit breaker," effectively a partial lockdown of the country, has further limited our work to only the most essential of services. Our staff are also increasingly part of frontline efforts in the screening and care of patients with COVID-19. However, this crisis has also been an opportunity to push ahead with innovative practices and given momentum to the use of teleophthalmology and other digital technologies. Amidst this uncertainty, our centers are already planning for how ophthalmology in Singapore will be practiced in this next stage of the COVID-19 pandemic, and beyond.

Optical Coherence Tomography Angiography of Optic Disc and Macula Vessel Density in Glaucoma and Healthy Eyes.

AIM: To study the microvascular density of the macular and optic nerve head in healthy and glaucoma subjects using optical coherence tomography angiography. METHODOLOGY: We performed a cross-sectional cohort study on healthy subjects and patients with glaucoma. The AngioVue Enhanced Microvascular Imaging System was used to capture the optic nerve head and macula images during one visit. En face segment images of the macular and optic disc were studied in layers. Microvascular density of the optic nerve head and macula were quantified by the number of pixels measured by a novel in-house developed software. Areas under the receiver operating characteristic curves (AUROC) were used to determine the accuracy of differentiating between glaucoma and healthy subjects. RESULTS: A total of 24 (32 eyes) glaucoma subjects (57.5±9.5-y old) and 29 (58 eyes) age-matched controls (51.17±13.5-y old) were recruited. Optic disc and macula scans were performed showing a greater mean vessel density (VD) in healthy compared with glaucoma subjects. The control group had higher VD than the glaucoma group at the en face segmented layers of the optic disc (optic nerve head: 0.209±0.05 vs. 0.110±0.048, P<0.001; vitreoretinal interface: 0.086±0.045 vs. 0.052±0.034, P=0.001; radial peripapillary capillary: 0.146±0.040 vs. 0.053±0.036, P<0.001; and choroid: 0.228±0.074 vs. 0.165±0.062, P<0.001). Similarly, the VD at the macula was also greater in controls than glaucoma patients (superficial retina capillary plexus: 0.115±0.016 vs. 0.088±0.027, P<0.001; deep retina capillary plexus: 0.233±0.027 vs. 0.136±0.073, P<0.001; outer retinal capillary plexus: 0.190±0.057 vs. 0.136±0.105, P=0.036; and choriocapillaris: 0.225±0.053 vs. 0.153±0.068, P<0.001. The AUROC was highest for optic disc radial peripapillary capillary (0.96), followed by nerve head (0.92) and optic disc choroid (0.76). At the macula, the AUROC was highest for deep retina (0.86), followed by choroid (0.84), superficial retina (0.81), and outer retina (0.72). CONCLUSIONS: Microvascular density of the optic disc and macula in glaucoma patients was reduced compared with healthy controls. VD of both optic disc and macula had a high diagnostic ability in differentiating healthy and glaucoma eyes.

Optical coherence tomography angiography of the macula and optic nerve head: microvascular density and test-retest repeatability in normal subjects.

BACKGROUND: Despite the potential usefulness of optical coherence tomography angiography in retinal and optic disc conditions, the reliability of the imaging modality remains unclear. This study set out to measure the microvascular density of macula and optic disc by mean of optical coherence tomography angiography and report the repeatability of the vessel density measurements. METHODS: Cross sectional observational cohort study. Subjects with normal eyes were recruited. Two sets of optical coherence tomography angiography images of macula and optic nerve head were acquired during one visit. Novel in-house developed software was used to count the pixels in each images and to compute the microvessel density of the macula and optic disc. Data were analysed to determine the measurement repeatability. RESULTS: A total of 176 eyes from 88 consecutive normal subjects were recruited. For macular images, the mean vessel density at superficial retina, deep retina, outer retina and choriocapillaries segment was OD 0.113 and OS 0.111, OD 0.239 and OS 0.230, OD 0.179 and OS 0.164, OD 0.237 and OS 0.215 respectively. For optic disc images, mean vessel density at vitreoretinal interface, radial peripapillary capillary, superficial nerve head and disc segment at the level of choroid were OD 0.084 and OS 0.085, OD 0.140 and OS 0.138, OD 0.216 and OS 0.209, OD 0.227 and OS 0.236 respectively. The measurement repeatability tests showed that the coefficient of variation of macular scans, for right and left eyes, ranged from 6.4 to 31.1% and 5.3 to 59.4%. Likewise, the coefficient of variation of optic disc scans, for right and left eyes, ranged from 14.3 to 77.4% and 13.5 to 75.3%. CONCLUSIONS: Optical coherence tomography angiography is a useful modality to visualise the microvasculature plexus of macula and optic nerve head. The vessel density measurement of macular scan by mean of optical coherence tomography angiography demonstrated good repeatability. The optic disc scan, on the other hand, showed a higher coefficient of variation indicating a lower measurement repeatability than macular scan. Interpretation of optical coherence tomography angiography should take into account test-retest repeatability of the imaging system. TRIAL REGISTRATION: National Healthcare Group Domain Specific Review Board ( NHG DSRB ) Singapore. DSRB Reference: 2015/00301.

Residual Angle Closure One Year After Laser Peripheral Iridotomy in Primary Angle Closure Suspects.

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.

Cost-effectiveness of a National Telemedicine Diabetic Retinopathy Screening Program in Singapore.

PURPOSE: To determine the incremental cost-effectiveness of a new telemedicine technician-based assessment relative to an existing model of family physician (FP)-based assessment of diabetic retinopathy (DR) in Singapore from the health system and societal perspectives. DESIGN: Model-based, cost-effectiveness analysis of the Singapore Integrated Diabetic Retinopathy Program (SiDRP). PARTICIPANTS: A hypothetical cohort of patients aged 55 years with type 2 diabetes previously not screened for DR. METHODS: The SiDRP is a new telemedicine-based DR screening program using trained technicians to assess retinal photographs. We compared the cost-effectiveness of SiDRP with the existing model in which FPs assess photographs. We developed a hybrid decision tree/Markov model to simulate the costs, effectiveness, and incremental cost-effectiveness ratio (ICER) of SiDRP relative to FP-based DR screening over a lifetime horizon. We estimated the costs from the health system and societal perspectives. Effectiveness was measured in terms of quality-adjusted life-years (QALYs). Result robustness was calculated using deterministic and probabilistic sensitivity analyses. MAIN OUTCOME MEASURES: The ICER. RESULTS: From the societal perspective that takes into account all costs and effects, the telemedicine-based DR screening model had significantly lower costs (total cost savings of S$173 per person) while generating similar QALYs compared with the physician-based model (i.e., 13.1 QALYs). From the health system perspective that includes only direct medical costs, the cost savings are S$144 per person. By extrapolating these data to approximately 170 000 patients with diabetes currently being screened yearly for DR in Singapore's primary care polyclinics, the present value of future cost savings associated with the telemedicine-based model is estimated to be S$29.4 million over a lifetime horizon. CONCLUSIONS: While generating similar health outcomes, the telemedicine-based DR screening using technicians in the primary care setting saves costs for Singapore compared with the FP model. Our data provide a strong economic rationale to expand the telemedicine-based DR screening program in Singapore and elsewhere.

Genome-wide association study identifies five 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 (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.

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.

Evaluation of the use of a nurse-administered telephone questionnaire for post-operative cataract surgery review.

PURPOSE: The purpose of this paper is to determine the safety of substituting the first day post-operative review after routine cataract surgery (phacoemulsification) with a telephone survey. DESIGN/METHODOLOGY/APPROACH: Prospective non-randomised cohort study. A standardised questionnaire of five common ocular symptoms (general condition, vision, eye pain, headache, nausea or vomiting) was administered by a trained nurse on the first post-operative day. The patients were reviewed in clinic two to 14 days later. Patient charts were retrospectively reviewed for complications (endophthalmitis, raised intra-ocular pressure, wound leaks and uveitis) requiring deviation from standard treatment. FINDINGS: Over 13 months, 256 eyes of 238 patients underwent uncomplicated phacoemulsification by four consultant surgeons. Only one patient reported poor general condition, blurred vision and eye pain. She was subsequently found to have corneal oedema and raised intra-ocular pressure when recalled for an earlier review. Best corrected visual acuity better than 20/40 was achieved in 80.5 per cent of patients. There were no other post-operative complications noted from medical records review. RESEARCH LIMITATIONS/IMPLICATIONS: Non-randomised nature, skewed surgical expertise, lack of a control group and patient experience data. In all, 22 patients (9.2 per cent) were also uncontactable for the telephone interview. PRACTICAL IMPLICATIONS: A nurse-administered telephone survey seemed to be a safe and effective alternative to first day post-operative review after routine phacoemulsification. The survey also enabled the detection of serious post-operative complications. The first day post-operative hospital visit may be safely substituted in a selected patient population with greater patient convenience achieved and liberation of clinic resources. ORIGINALITY/VALUE: This is the first study which utilises a standardised questionnaire as a form of post-operative review in an Asian population.

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.

Angle closure glaucoma detection using fractal dimension index on SS-OCT images.

Optical coherence tomography (OCT) is a high resolution, rapid and non-invasive screening tool for angle closure glaucoma. In this paper, we propose a new strategy for automatic and landmark invariant quantification of the anterior chamber angle of the eye using swept source optical coherence tomography (SS-OCT) images. Seven hundred and eight swept source optical coherence tomography SS-OCT images from 148 patients with average age of (59.48 ± 8.97) were analyzed in this study. The angle structure is measured by fractal dimension (FD) analysis to quantify the complexity or changes of angle recess. We evaluated the FD index with biometric parameters for classification of open angle and angle closure glaucoma. The proposed fractal dimension index gives a better representation of the angle configuration for capturing the nature of the angle dynamics involved in different forms of open and closed angle glaucoma (average FD (standard deviation): 1.944 (0.045) for open and 1.894 (0.043) for closed angle). It showed that the proposed approach has promising potential to become a computer aided diagnostic tool for angle closure glaucoma (ACG) disease.

Effect of prophylactic laser iridotomy on corneal endothelial cell density over 3 years in primary angle closure suspects.

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.

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.

Changes in anterior segment morphology after laser peripheral iridotomy: an anterior segment optical coherence tomography study.

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 (ß = 0.286, P = 0.001), mean IT at 2000 µm (IT2000, ß = 0.172, P = 0.034), and intraocular pressure (ß = 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.

Risk of acute angle closure and changes in intraocular pressure after pupillary dilation in Asian subjects with narrow angles.

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 ß -0.51; standard error 0.19; P=0.01), and predilation IOP level (coefficient ß -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.

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: Schwalbe's line. This paper presents a novel algorithm which automatically detects Schwalbe's 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 Schwalbe's line bounded area (SLBA).