Angle closure extent, anterior segment dimensions and intraocular pressure.

AIM: To investigate the association between the extent of iridotrabecular contact and other quantitative anterior segment dimensions measured by swept-source optical coherence tomography (SS-OCT; CASIA SS-1000, Tomey, Nagoya, Japan) with intraocular pressure (IOP). METHODS: Cross-sectional study. All subjects who were ≥50 years with no history of glaucoma, ocular surgery or trauma, underwent SS-OCT imaging (eight equally spaced radial scans), Goldman applanation tonometry and gonioscopy on the same day. We measured iridotrabecular contact (ITC) index and area, total volume of trabeculo-iris space area and angle opening distance at 500 and 750 from the scleral spur (TISA 500 and 750, AOD 500 and 750, respectively), anterior chamber depth (ACD), volume, area and width, pupil diameter, lens vault and iris volume.Their relationship with IOP (dependent variable) was assessed by locally weighted scatterplot smoothing (Lowess) regression with change-point analysis and generalised additive models adjusted for confounders. RESULTS: 2027 right eyes of mostly Chinese Singaporeans (90%) were analysed. ITC index above a threshold of ~60% (95% CI 34% to 92%) was significantly associated with higher IOP. Independent of the extent of ITC, ACD was also significantly associated with higher IOP below a threshold of 2.5 mm (95% CI 2.33 mm to 2.71 mm). Greater ITC index and shallower ACD had a joint association with IOP. A model including ACD and ITC index was more predictive of IOP than a model considering these variables separately, particularly for women with gonioscopically closed angles (R2 52.7%, p<0.05). CONCLUSIONS: The extent of angle closure and the ACD below a certain threshold had a significant joint association with IOP. These parameters, as biometrical surrogates of mechanical obstruction of the aqueous outflow, may jointly contribute to elevated IOP, particularly in women with gonioscopic angle closure.

A comparative analysis of surgical outcome in uveitic and non-uveitic steroid-induced glaucoma in children.

Purpose: To compare outcomes of surgical management of uveitic glaucoma (UG) and steroid-induced glaucoma (SIG) in children in terms of intraocular pressure (IOP) control, visual acuity, and associations for failure. Methods: This was a retrospective case-control study of consecutive UG (cases) and non-uveitic SIG (controls) in children <18 years of age who underwent surgery between January 2005 and December 2017. Results: Primary trabeculectomy with mitomycin C (MMC) was performed in 12 cases (mean age: 9.2 ± 4.3 years) and 40 controls (mean age: 10.4 ± 3.7 years) (P = 0.33). Primary phaco-trabeculectomy with MMC was performed in 11 cases (mean age: 11.4 ± 4.7 years) and 16 controls (mean age: 10.4 ± 3.4 years) (P = 0.57). IOP control (P = 0.26), visual acuity (P = 0.97), number of glaucoma medications (P = 0.06), and survival rates (49% cases vs. 68% controls at 5 years; P = 0.22) were similar between the two groups following trabeculectomy. Survival rates in the phaco-trabeculectomy group at 5 years were 68% cases vs. 69% controls (P = 0.71). IOP was higher (P = 0.008) and visual acuity was worse (P = 0.02) in cases at the last visit. Associations for failure (univariate analysis) were younger age (OR: 6.29, 95% CL: 1.43, 27.67; P = 0.03) and male gender (OR: 4.79, 95% CL: 1.09, 20.97; P = 0.04). On multivariate analysis, younger age (OR: 11.985, 95% CL: 1.071, 134.153; P = 0.04) remained significant. Preoperative number of uveitic attacks was protective on univariate (OR: 0.75, 95% CL: 0.48, 1.15; P = 0.1) and multivariate analyses (OR: 0.49, 95% CL: 0.24, 0.09; P = 0.04). Conclusion: Outcomes of trabeculectomy between cases and controls were similar in our series. However, phaco-trabeculectomy in pediatric uveitic eye group fared worse than eyes with SIG.

Towards 'automated gonioscopy': a deep learning algorithm for 360° angle assessment by swept-source optical coherence tomography.

AIMS: To validate a deep learning (DL) algorithm (DLA) for 360° angle assessment on swept-source optical coherence tomography (SS-OCT) (CASIA SS-1000, Tomey Corporation, Nagoya, Japan). METHODS: This was a reliability analysis from a cross-sectional study. An independent test set of 39 936 SS-OCT scans from 312 phakic subjects (128 SS-OCT meridional scans per eye) was analysed. Participants above 50 years with no previous history of intraocular surgery were consecutively recruited from glaucoma clinics. Indentation gonioscopy and dark room SS-OCT were performed. Gonioscopic angle closure was defined as non-visibility of the posterior trabecular meshwork in ≥180° of the angle. For each subject, all images were analysed by a DL-based network based on the VGG-16 architecture, for gonioscopic angle-closure detection. Area under receiver operating characteristic curves (AUCs) and other diagnostic performance indicators were calculated for the DLA (index test) against gonioscopy (reference standard). RESULTS: Approximately 80% of the participants were Chinese, and more than half were women (57.4%). The prevalence of gonioscopic angle closure in this hospital-based sample was 20.2%. After analysing a total of 39 936 SS-OCT scans, the AUC of the DLA was 0.85 (95% CI:0.80 to 0.90, with sensitivity of 83% and a specificity of 87%) to classify gonioscopic angle closure with the optimal cut-off value of >35% of circumferential angle closure. CONCLUSIONS: The DLA exhibited good diagnostic performance for detection of gonioscopic angle closure on 360° SS-OCT scans in a glaucoma clinic setting. Such an algorithm, independent of the identification of the scleral spur, may be the foundation for a non-contact, fast and reproducible 'automated gonioscopy' in future.

Assessment of Circumferential Angle Closure with Swept-Source Optical Coherence Tomography: a Community Based Study.

PURPOSE: To evaluate the diagnostic performance of swept-source optical coherence tomography (SS-OCT, CASIA SS-1000; Tomey Corporation, Nagoya, Japan) for angle closure detection, in comparison with gonioscopy, in a community setting. DESIGN: Reliability analysis. METHODS: A total of 2027 phakic subjects aged ≥50 years, with no previous history of glaucoma, laser (including peripheral iridotomy), intraocular surgery, or ocular trauma, were consecutively recruited from a community polyclinic in Singapore. Gonioscopy was performed by a single trained ophthalmologist. SS-OCT angle scans, which obtain radial scans for the entire circumference of the angle, were analyzed by a single examiner, masked to the subject's clinical details. On SS-OCT images, angle closure was defined as contact between the iris and any part of the angle wall anterior to the scleral spur. Different cutoff values of the degree of circumferential angle closure (≥35%, ≥50%, and ≥75%) were taken for analysis to assess SS-OCT performance in detecting angle closure. RESULTS: A total of 1857 subjects (91.6%) were included in the final analysis after excluding poor-quality SS-OCT scans. Almost 90% of the subjects were Chinese, with a mean age of 61.8 ± 6.7 years, and more than half were women (63.5%). The overall AUC of SS-OCT manual grading against gonioscopy was 0.84 (95% confidence interval, 0.81-0.88). The prevalence of angle closure on SS-OCT was 26.1% for the ≥35% definition, with an area under the curve of 0.80 (0.77-0.84), sensitivity of 82.5% (75.3%-88.4%), and specificity of 78.5% (76.5%-80.4%). The first-order agreement coefficient statistics for the 2-quadrant gonioscopic definition of angle-closure with corresponding ≥35%, ≥50%, and ≥75% angle closure definitions for SS-OCT were good at 0.89 (0.83-0.93), 0.88 (0.842-0.93), and 0.88 (0.831-0.99), respectively. CONCLUSIONS: In this large community-based study, SS-OCT exhibited moderate performance for angle closure detection compared to gonioscopy as the reference standard.

Anterior segment optical coherence tomography.

Optical coherence tomography (OCT) provides non-contact, rapid in vivo imaging of ocular structures, and has become a key part of evaluating the anterior segment of the eye. Over the years, improvements to technology have increased the speed of capture and resolution of images, leading to the increasing impact of anterior segment OCT imaging on clinical practice. In this review, we summarize the historical development of anterior segment OCT, and provide an update on the research and clinical applications of imaging the ocular surface, cornea, anterior chamber structures, aqueous outflow system, and most recently anterior segment vessels. We also describe advancements in anterior segment OCT technology that have improved understanding with greater detail, such as tear film in dry eye disease evaluation, intra-operative real-time imaging for anterior segment surgery, and aqueous outflow with angle assessment for glaucoma. Improvements to image processing and software have also improved the ease and utility of interpreting anterior segment OCT images in everyday clinical practice. Future developments include refinement of assessing vascular networks for the anterior segment, in vivo ultra-high resolution anterior segment optical coherence tomography with histology-like detail, en-face image with 3-dimensional reconstruction as well as functional extensions of the technique.

Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma.

Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide for which 15 disease-associated loci had been discovered. Among them, only 5 loci have been associated with POAG in Asians. We carried out a genome-wide association study and a replication study that included a total of 7378 POAG cases and 36 385 controls from a Japanese population. After combining the genome-wide association study and the two replication sets, we identified 11 POAG-associated loci, including 4 known (CDKN2B-AS1, ABCA1, SIX6 and AFAP1) and 7 novel loci (FNDC3B, ANKRD55-MAP3K1, LMX1B, LHPP, HMGA2, MEIS2 and LOXL1) at a genome-wide significance level (P < 5.0×10-8), bringing the total number of POAG-susceptibility loci to 22. The 7 novel variants were subsequently evaluated in a multiethnic population comprising non-Japanese East Asians (1008 cases, 591 controls), Europeans (5008 cases, 35 472 controls) and Africans (2341 cases, 2037 controls). The candidate genes located within the new loci were related to ocular development (LMX1B, HMGA2 and MAP3K1) and glaucoma-related phenotypes (FNDC3B, LMX1B and LOXL1). Pathway analysis suggested epidermal growth factor receptor signaling might be involved in POAG pathogenesis. Genetic correlation analysis revealed the relationships between POAG and systemic diseases, including type 2 diabetes and cardiovascular diseases. These results improve our understanding of the genetic factors that affect the risk of developing POAG and provide new insight into the genetic architecture of POAG in Asians.

Social, health and ocular factors associated with primary open-angle glaucoma amongst Chinese Singaporeans.

IMPORTANCE: There is limited literature on lifestyle and health factors related to primary open-angle glaucoma amongst Asians. BACKGROUND: This study evaluated the association of primary open-angle glaucoma with smoking, health and ocular factors amongst Chinese Singaporeans. DESIGN: Case-control study. PARTICIPANTS: The study used 711 primary open-angle glaucoma patients from a Singapore hospital and 2788 population-based controls. METHODS: Subjects underwent clinical examination and completed a questionnaire with details on family history of glaucoma, comorbidities, smoking and alcohol consumption. Glaucoma cases were subclassified as normal or high-tension glaucoma according to their untreated intraocular pressures. MAIN OUTCOME MEASURES: The association of various health and lifestyle factors, with normal-tension and high-tension glaucoma was evaluated. RESULTS: Using multiple logistic regression, primary open-angle glaucoma was associated with older age (odds ratio 1.12 per year older; 95% confidence interval 1.10-1.15; P < 0.001), family history of glaucoma (odds ratio 7.86; 95% confidence interval 4.48-13.79; P < 0.001), higher intraocular pressure (odds ratio 1.75 per 1 mmHg; 95% confidence interval 1.64-1.87; P < 0.001) and thinner central corneal thickness (odds ratio 1.01; 95% confidence interval 1.01-1.02; P < 0.001). Myopes were more likely to have primary open-angle glaucoma (P < 0.001). A current smoking habit was protective against normal-tension glaucoma (odds ratio 0.30; 95% confidence interval 0.10-0.92; P = 0.035). CONCLUSIONS AND RELEVANCE: Older age, family history of glaucoma, higher intraocular pressure, thinner central corneal thickness and myopia were significantly associated with primary open-angle glaucoma amongst Chinese Singaporeans.

Primary angle closure glaucoma (PACG) susceptibility gene PLEKHA7 encodes a novel Rac1/Cdc42 GAP that modulates cell migration and blood-aqueous barrier function.

PLEKHA7, a gene recently associated with primary angle closure glaucoma (PACG), encodes an apical junctional protein expressed in components of the blood aqueous barrier (BAB). We found that PLEKHA7 is down-regulated in lens epithelial cells and in iris tissue of PACG patients. PLEKHA7 expression also correlated with the C risk allele of the sentinel SNP rs11024102 with the risk allele carrier groups having significantly reduced PLEKHA7 levels compared to non-risk allele carriers. Silencing of PLEKHA7 in human immortalized non-pigmented ciliary epithelium (h-iNPCE) and primary trabecular meshwork cells, which are intimately linked to BAB and aqueous humor outflow respectively, affected actin cytoskeleton organization. PLEKHA7 specifically interacts with GTP-bound Rac1 and Cdc42, but not RhoA, and the activation status of the two small GTPases is linked to PLEKHA7 expression levels. PLEKHA7 stimulates Rac1 and Cdc42 GTP hydrolysis, without affecting nucleotide exchange, identifying PLEKHA7 as a novel Rac1/Cdc42 GAP. Consistent with the regulatory role of Rac1 and Cdc42 in maintaining the tight junction permeability, silencing of PLEKHA7 compromises the paracellular barrier between h-iNPCE cells. Thus, downregulation of PLEKHA7 in PACG may affect BAB integrity and aqueous humor outflow via its Rac1/Cdc42 GAP activity, thereby contributing to disease etiology.

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.

Pupillary responses to light are not affected by narrow irido-corneal angles.

Chromatic pupillometry is an emerging method for evaluating ocular health that relies upon the differential stimulation of rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). Although it has been investigated in conditions affecting the outer or inner retina, there is a paucity of studies in conditions where the anterior chamber of the eye is affected. Primary angle closure suspects (PACS) are defined as eyes with narrow anterior chamber angles and intact retina. PACS patients are at risk of developing primary angle closure glaucoma and are prophylactically treated by performing laser peripheral iridotomy (LPI). Here we evaluated pupillary responses to monchromatic lights in 18 PACS before and after LPI, and compared the results with those of 36 age-matched controls who had gonioscopically open angles. Dose response curves for pupillary constriction were similar between PACS patients and controls (p = 0.98 for blue and 0.90 for red light) and within subjects pre- and post-LPI (p = 0.58 for blue and 0.20 for red light). Baseline-adjusted pupillary constriction responses to blue and red lights were similar in controls and PACS, and not altered after LPI. Our findings suggest that narrow irido-corneal angles and LPI do not influence pupillary responses in PACS.

Intraocular pressure change after phacoemulsification in angle-closure eyes without medical therapy.

PURPOSE: To evaluate the intraocular pressure (IOP) change and associated factors 6 months after phacoemulsification in eyes with primary angle-closure suspect (PACS) and eyes with primary angle closure (PAC) that had no medical therapy. SETTING: Singapore National Eye Center, Singapore, Singapore. DESIGN: Retrospective case series. METHODS: Patients with PACS or PAC (with corrected distance visual acuity <20/40) who had uneventful phacoemulsification were recruited. Patients were excluded if they were on IOP-lowering medications within 6 months preoperatively and postoperatively. Preoperative gonioscopy, A-scan biometry, anterior segment optical coherence tomography, and automated refraction were reviewed. Factors related to the percentage of and absolute IOP change were assessed using multiple linear regression analyses after adjusting for age, sex, and diagnosis. RESULTS: The study evaluated 85 patients (85 eyes; 52 PACS, 33 PAC) after 7 eyes (1 PACS, 6 PAC) were excluded because of poor quality imaging. Overall, IOP decreased by 19.9% from the preoperative mean of 16.1 mm Hg ± 3.1 (SD) to 12.9 ± 2.7 mm Hg. The IOP change between the PACS group (-3.3 ± 2.8 mm Hg; -20.6%) and the PAC group (-3.2 ± 4.7 mm Hg; -19.6%) was similar (P > .05). In multiple linear regression analyses, a higher preoperative IOP (ß = 0.68, P < .001) and fewer clock hours of peripheral anterior synechiae (PAS) (ß = -0.30, P = .03) predicted a greater absolute change in and percentage of reduction in IOP, respectively. CONCLUSIONS: The mean IOP reduction 6 months after phacoemulsification was 20%. Less IOP reduction was observed in the presence of lower preoperative IOP and more extensive PAS.

Argon Laser Peripheral Iridoplasty for Primary Angle-Closure Glaucoma: A Randomized Controlled Trial.

PURPOSE: To determine the effectiveness of argon laser peripheral iridoplasty (ALPI) in primary angle closure (PAC) and primary angle-closure glaucoma (PACG). DESIGN: Randomized controlled trial. PARTICIPANTS: Eighty PAC or PACG subjects who underwent laser iridotomy (LI) and had at least 180° of persistent appositional angle closure and intraocular pressure (IOP) of more than 21 mmHg were enrolled. METHODS: Subjects were randomized to receive either 360° ALPI (Visulas 532s; Carl Zeiss Meditec, Jena, Germany) or medical therapy (Travoprost 0.004%; Alcon-Couvreur, Puurs, Antwerp, Belgium). Repeat ALPI was performed if the IOP reduction was less than 20% from baseline along with inadequate angle widening at the month 1 or month 3 visit. Intraocular pressure was controlled with systematic addition of medications when required. MAIN OUTCOME MEASURES: The primary outcome measure was success rates after ALPI at 1 year. Complete success was defined as an IOP of 21 mmHg or less without medication, and qualified success was defined as an IOP of 21 mmHg or less with medication. Failure was defined as an IOP more than 21 mmHg despite additional medications or requiring glaucoma surgery. RESULTS: Forty subjects (51 eyes) were randomized to ALPI and 40 subjects (55 eyes) were randomized to medical therapy. Complete success (IOP ≤21 mmHg without medication) was achieved in 35.0% eyes of the ALPI group compared with 85.0% of eyes in the prostaglandin analog (PGA) group (P < 0.001), and qualified success (IOP ≤21 mmHg with medication) was achieved in 35.0% and 7.5%, respectively (P = 0.003). The IOP decreased by 4.9 mmHg (95% confidence interval [CI], 3.5-6.3 mmHg) in the ALPI group (P < 0.001) and by 6.1 mmHg (95% CI, 5.1-7.1 mmHg) in the medication group (P < 0.001). A failure rate of 30.0% was noted in the ALPI group compared with 7.5% in the medication group (P = 0.01). No treatment-related complications were recorded in either group. CONCLUSIONS: After 1 year, ALPI was associated with higher failure rates and lower IOP reduction compared with PGA therapy in eyes with persistent appositional angle closure and raised IOP after LI.

Prevalence, Risk Factors, and Visual Features of Undiagnosed Glaucoma: The Singapore Epidemiology of Eye Diseases Study.

IMPORTANCE: Glaucoma can remain asymptomatic until a severe stage, resulting in a high prevalence of undiagnosed glaucoma worldwide. Asia accounts for 60% of the world's total glaucoma cases. To our knowledge, no epidemiological studies have assessed ethnic differences in undiagnosed glaucoma among various Asian subgroups. OBJECTIVE: To determine the prevalence of, risk factors for, and visual features of undiagnosed primary glaucoma in a multiethnic Asian population. DESIGN, SETTING, AND PARTICIPANTS: The Singapore Epidemiology of Eye Diseases Study is a population-based trial in which 3353 Chinese (2009-2011), 3280 Malays (2004-2006), and 3400 Indians (2007-2009) aged 40 to 80 years were invited for an eye examination, including visual field assessment, to establish glaucoma diagnosis. Participants with undiagnosed glaucoma (ie, answering no to whether they previously had been told by a physician that they had glaucoma, not using glaucoma medication, or not having undergone glaucoma surgery) were identified. MAIN OUTCOMES AND MEASURES: Prevalence of, risk factors for, and visual features of undiagnosed glaucoma. RESULTS: Of 272 participants with primary glaucoma, 196 (72.1%) were previously undiagnosed. The overall prevalence of undiagnosed primary glaucoma was highest among Malays (2.65%; 95% CI, 2.10%-3.31%), followed by Chinese (1.51%; 95% CI, 1.13%-2.01%) and Indians (0.97%; 95% CI, 0.64%-1.43%). In multivariable analysis, variables associated with higher risk of undiagnosed glaucoma were younger age (odds ratio [OR], 1.04; 95% CI, 1.00-1.09; P = .04), Malay ethnicity (OR, 3.65; 95% CI, 1.31-10.13; P = .01), presence of primary open-angle glaucoma (OR, 3.82; 95% CI, 1.60-9.14; P = .003), absence of yearly eyeglass checks (OR, 9.29; 95% CI, 3.43-25.21; P < .001), and lack of cataract surgery (OR, 4.19; 95% CI, 1.68-10.48; P < .001). No patients were blind in both eyes. A mean (SD) of 4.1% (2.8%) (n = 8) of the newly diagnosed patients were blind in 1 eye, and a mean (SD) of 56.0% (7.2%) (n = 102) had noteworthy visual field damage (mean deviation worse than -6 dB) in at least 1 eye. CONCLUSIONS AND RELEVANCE: The prevalence of undiagnosed primary glaucoma varied among ethnic populations in whom a mean (SD) of 49.0% (14.0%) (n = 24) of affected individuals 50 to 59 years old already had clinically significant visual field loss. Such data may assist policymakers in implementing cost-effective public health interventions to reduce the effect of blindness associated with undiagnosed glaucoma.

Swept-source optical coherence tomography assessment of iris-trabecular contact after phacoemulsification with or without goniosynechialysis in eyes with primary angle closure glaucoma.

AIMS: To compare the change in iris-trabecular contact (ITC) area using swept-source optical coherence tomography (SS-OCT) in eyes with primary angle closure glaucoma (PACG) and cataract that underwent phacoemulsification (PE) with intraocular lens implantation alone compared with PE with goniosynechialysis (GSL). METHODS: One eye of 22 patients with PACG with peripheral anterior synechiae (PAS) detected by indentation gonioscopy was randomised into two groups (PE alone (n=11) and PE+GSL (n=11)). The anterior chamber angles were evaluated by SS-OCT under dark conditions before and 12 months after surgery using the three-dimensional angle analysis scan protocol that simultaneously obtains 128 cross-sectional radial scans across the anterior chamber at equal intervals (every 1.4°). The ITC area, defined as the area of extent of the circumferential contact of peripheral iris to the angle wall, was computed automatically by SS-OCT after an observer marked the scleral spurs of all 128 scans of each eye. RESULTS: The majority of the 22 subjects were women (77.3%) and the mean±SD age was 67.3±5.8 years. The ITC area was significantly reduced in the PE+GSL group compared with the PE alone group (10.2 mm2 vs. 4.6 mm2, ß=0.54, p=0.03) after adjusting for age, gender, intraocular pressure, extent of PAS and pupil diameter before surgery. Smaller iris volume at baseline was associated with greater ITC area reduction by PE+GSL (ß=-0.728, p=0.03). CONCLUSIONS: Eyes that undergo PE+GSL surgery have a greater reduction in circumferential ITC area than eyes that undergo PE alone.

Efficacy of selective laser trabeculoplasty in primary angle-closure glaucoma: a randomized clinical trial.

IMPORTANCE: Selective laser trabeculoplasty (SLT) should be explored as a therapeutic option in eyes with angle closure. OBJECTIVE: To assess the intraocular pressure (IOP)-lowering efficacy of SLT in eyes with primary angle closure (PAC) and PAC glaucoma (PACG). DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial at tertiary eye care institutions of 100 patients diagnosed as having PAC or PAC glaucoma in which the angles had opened at least 180° (visible posterior trabecular meshwork on gonioscopy) after laser iridotomy. Recruitment and baseline were completed from June 2009 to April 2012 and 6-month follow-up was completed from December 2009 to November 2012. INTERVENTIONS: Eligible patients with a baseline IOP greater than 21 mm Hg were randomized to either SLT or prostaglandin analog (PGA; travoprost, 0.004%). The SLT was repeated if the IOP reduction was less than 20.0% from baseline at the 1- or 3-month follow-up visit. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the change in IOP from baseline to the final follow-up visit (at 6 months). The frequency of additional postoperative treatments and complications were secondary outcomes. RESULTS: Fifty patients (96 eyes) were randomized to SLT and 50 patients (99 eyes) to PGA medical therapy. At 6 months, 49 patients in the SLT group and 47 in the PGA group completed follow-up. Analysis was based on intent to treat. At 6 months, IOP decreased by 4.0 mm Hg (95% CI, 3.2-4.8) in the SLT group (P < .001) and by 4.2 mm Hg (95% CI, 3.5-4.9) in the PGA group (P < .001). There were no differences between the SLT and PGA groups in the absolute mean reduction of IOP (4.0 vs 4.2 mm Hg, respectively; P = .78) or in the percentage of reduction in IOP (16.9% vs 18.5%, respectively; P = .52). Complete success (IOP ≤21 mm Hg without medications) was achieved in 60.0% eyes of the SLT group, compared with 84.0% of eyes in the PGA group (P = .008). No patients required glaucoma surgery. Additional medications were required in 22.0% of patients in the SLT group compared with 8.0% in the PGA group (P = .05). One patient in the SLT group (2.0%) had a transient posttreatment IOP spike greater than 5 mm Hg. The mean endothelial cell count showed a significant decrease from baseline in the SLT arm (4.8% decrease; P = .001). No other events such as persistent uveitis or increase in peripheral anterior synechiae were noted in eyes that underwent SLT. Two patients in the PGA group exited owing to drug-related complications (1 patient with uveitis and 1 with allergic conjunctivitis). CONCLUSIONS AND RELEVANCE: Eyes with PAC or PACG respond to SLT in the short term, but the overall long-term therapeutic effectiveness needs further evaluation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01004900.

Genotype-phenotype correlation analysis for three primary angle closure glaucoma-associated genetic polymorphisms.

PURPOSE: Recently, three genetic susceptibility loci for primary angle closure glaucoma (PACG) were identified: COL11A1 rs3753841, PCMTD1-ST18 rs1015213, and PLEKHA7 rs11024102. The purpose of this study was to investigate whether these single nucleotide polymorphisms (SNPs) affect the phenotype of PACG patients. METHODS: A retrospective analysis was performed for 700 Singaporean Chinese PACG patients who had been genotyped. The associations between the three SNPs and clinical features related to severity of glaucoma were studied. For a subgroup of patients who had ≥ 5 years of follow-up and ≥ 5 reliable visual field (VF) tests, differences in glaucoma progression, as measured by the proportion of VF progression and blindness, were compared among groups with different genotypes. RESULTS: The minor allele frequencies at COL11A1 rs3753841, PCMTD1-ST18 rs1015213, and PLEKHA7 rs11024102 were 36%, 2.1%, and 41.5%, respectively. There were no significant differences in sex, diagnosis (acute primary angle closure [APAC] versus non-APAC), age at diagnosis, laterality of glaucoma, or need for filtration surgery among patients with different genotypes (all P > 0.05). We also found no significant difference between genotypes and the IOP at presentation, and other clinical characteristics at DNA collection (vertical cup-to-disc ratio, best corrected visual acuity, baseline VF mean deviation, or pattern standard deviation). For the subgroup analysis, we did not observe significant associations between VF progression and the proportion of blindness with any of the PACG susceptibility loci. CONCLUSIONS: The three genetic susceptibility loci for PACG did not underlie any major phenotypic diversity in terms of disease severity or progression.

Assessment of circumferential angle-closure by the iris-trabecular contact index with swept-source optical coherence tomography.

PURPOSE: To evaluate the diagnostic performance of the iris-trabecular contact (ITC) index, a measure of the degree of angle-closure, using swept-source optical coherence tomography (SSOCT, CASIA SS-1000, Tomey Corporation, Nagoya, Japan) in comparison with gonioscopy. DESIGN: Prospective observational study. PARTICIPANTS: A total of 108 normal subjects and 32 subjects with angle-closure. METHODS: The SSOCT 3-dimensional angle scans, which obtain radial scans for the entire circumference of the angle, were performed under dark conditions and analyzed using customized software by a single examiner masked to the subjects' clinical details. The ITC index was calculated as a percentage of the angle that was closed on SSOCT images. First-order agreement coefficient (AC1) statistics and area under the receiver operating characteristic curve (AUC) analyses were performed for angle-closure on the basis of the ITC index in comparison with gonioscopy. MAIN OUTCOME MEASURES: Angle-closure on gonioscopy was defined as nonvisibility of posterior trabecular meshwork for at least 2 quadrants. Agreement of the ITC index with gonioscopically defined angle-closure was assessed using the AC1 statistic. RESULTS: Study subjects were predominantly Chinese (95.7%) and female (70.7%), with a mean age of 59.2 (standard deviation, 8.9) years. The median ITC index was 15.24% for gonioscopically open-angle eyes (n = 108) and 48.5% for closed-angle eyes (n = 32) (P = 0.0001). The agreement for angle-closure based on ITC index cutoffs (>35% and ≥50%) and gonioscopic angle-closure was 0.699 and 0.718, respectively. The AUC for angle-closure detection using the ITC index was 0.83 (95% confidence interval, 0.76-0.89), with an ITC index >35% having a sensitivity of 71.9% and specificity of 84.3%. CONCLUSIONS: The ITC index is a summary measure of the circumferential extent of angle-closure as imaged with SSOCT. The index had moderate agreement and good diagnostic performance for angle-closure with gonioscopy as the reference standard.

Can intraocular pressure asymmetry indicate undiagnosed primary glaucoma? The Chennai Glaucoma Study.

AIM: : To investigate the association of intraocular pressure (IOP) asymmetry with undiagnosed primary glaucoma in rural and urban populations of south India. METHODS: Chennai Glaucoma Study is a population-based cross-sectional study. The participants were adults, 40 years or older. The prevalence of primary glaucoma was defined using International Society of Geographical and Epidemiological Ophthalmology classification. IOP asymmetry was diagnosed when the difference in IOP between 2 eyes was >3 mm Hg. Analysis included only bilaterally phakic subjects. We excluded subjects with known glaucoma, secondary glaucoma, pseudoexfoliation, ocular trauma, and ocular surgery. RESULTS: Of 6310 subjects, 3052 (48.4%) were rural residents. The mean age was 52 (standard deviation: 9.5) years. The prevalence of IOP asymmetry increased steadily with increasing patient age. The prevalence of undiagnosed primary glaucoma was 3.4% (95% confidence interval, 2.9-3.8). Undiagnosed primary glaucoma was 3 times more common in subjects with IOP asymmetry than without (odds ratio 3.08, 95% confidence interval, 2.1-4.3). The specificity of IOP asymmetry in detecting undiagnosed primary glaucoma was 92%. CONCLUSIONS: IOP asymmetry of >3 mm Hg has limited accuracy for the detection of undiagnosed primary glaucoma. The criterion should be combined with other indicators of glaucoma to build the pretest probability of the 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.

In vivo analysis of vectors involved in pupil constriction in Chinese subjects with angle closure.

PURPOSE: To evaluate the acceleration of pupil constriction (APC) in response to illumination using video anterior segment optical coherence tomography (AS-OCT) in angle closure and normal eyes. METHODS: This was an observational study of 342 Chinese subjects. Iris and angle changes in response to illumination were captured with real-time video recordings of AS-OCT and analyzed frame by frame. APC was calculated using a quadratic function, fitting pupil diameter to a time series. APC was divided into two vector components: acceleration of pupil block (APB) acting perpendicular to the lens surface and acceleration of iris stretch (AIS) acting toward the iris root. RESULTS: Of 342 eligible patients, 306 (89.5%) were available for analysis; of whom 136 (41.7%) had angle closure. After adjusting for age, sex, baseline pupil diameter, and iris thickness, APC was significantly lower in angle closure eyes (0.61 mm/s(2)) than in open-angle eyes (0.90 mm/s(2)) (P < 0.0001) as was AIS (0.58 mm/s(2) vs. 0.89 mm/s(2)) (P < 0.001). APB was significantly higher in angle closure eyes compared to open-angle eyes (0.14 mm/s(2) vs. 0.09 mm/s(2)) (P < 0.001). After adjusting for age and sex in logistic regression, the magnitude and direction of all vector parameters were significantly associated with presence of angle closure. CONCLUSIONS: Angle closure eyes have smaller AIS and larger APB in response to illumination as measured using AS-OCT videography. This shows that, comparatively, the iris of angle closure eyes stretches less and develops a more convex configuration in response to illumination.