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.

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.

Identification of four novel variants that influence central corneal thickness in multi-ethnic Asian populations.

Central corneal thickness (CCT) is a highly heritable trait. Genes that significantly influence CCT can be candidate genes for common disorders in which CCT has been implicated, such as primary open-angle glaucoma (POAG) and keratoconus. Because the genetic factors controlling CCT in different Asian populations are unclear, we have built on previous work conducted on Singaporean Indians and Malays and extended our hypothesis to individuals of Chinese descent. We have followed up on all suggestive signals of association with CCT (P < 10(-4)) from the previously reported meta-analysis comprising Indians and Malays in a sample of Chinese individuals (n= 2681). In the combined sample (n= 7711), strong evidence of association was observed at four novel loci: IBTK on chromosome 6q14.1; CHSY1 on chromosome 15q26.3; and intergenic regions on chromosomes 7q11.2 and 9p23 (8.01 × 10(-11) < λ(GC) corrected P(meta) < 8.72 × 10(-8)). These four new loci explain an additional 4.3% of the total CCT variance across the sample cohorts over and above that of previously identified loci. We also extend on a previous finding at a fifth locus (AKAP13) where a new single-nucleotide polymorphism (rs1821481, P(meta) = 9.99 × 10(-9)) was found to be significantly more informative compared with the previously reported rs6496932 (P(meta) = 3.64 × 10(-5)). Performing association analysis in Asians may lead to the discovery of ethnic-specific genes that control CCT, offering further mechanistic insights into the regulation of CCT. In addition, it may also provide several candidate genes for interrogation for POAG, keratoconus and possible racial/ethnic variations.

Six-Year Incidence and Risk Factors for Primary Open-Angle Glaucoma and Ocular Hypertension: The Singapore Epidemiology of Eye Diseases Study.

OBJECTIVE: To determine the incidence and risk factors for primary open-angle glaucoma (POAG) and ocular hypertension (OHT) in a multiethnic Asian population. DESIGN: Population-based cohort study. PARTICIPANTS: The Singapore Epidemiology of Eye Diseases study included 10 033 participants in the baseline examination between 2004 and 2011. Of those, 6762 (response rate = 78.8%) participated in the 6-year follow-up visit between 2011 and 2017. METHODS: Standardized examination and investigations were performed, including slit lamp biomicroscopy, intraocular pressure (IOP) measurement, pachymetry, gonioscopy, optic disc examination and static automated perimetry. Glaucoma was defined according to a combination of clinical evaluation, ocular imaging (fundus photo, visual field, and OCT) and criteria given by International Society of Geographical and Epidemiological Ophthalmology. OHT was defined on the basis of elevated IOP over the upper limit of normal; i.e., 20.4 mmHg, 21.5 mmHg, and 22.6 mmHg for the Chinese, Indian, and Malay cohort respectively, without glaucomatous optic disc change. MAIN OUTCOME MEASURES: Incidence of POAG, OHT, and OHT progression. RESULTS: The overall 6-year age-adjusted incidences of POAG and OHT were 1.31% (95% confidence interval [CI], 1.04-1.62) and 0.47% (95% CI, 0.30-0.70). The rate of progression of baseline OHT to POAG at 6 years was 5.32%. Primary open-angle glaucoma incidence was similar (1.37%) in Chinese and Indians and lower (0.80%) in Malays. Malays had higher incidence (0.79%) of OHT than Indians (0.38%) and Chinese (0.37%). Baseline parameters associated with higher risk of POAG were older age (per decade: odds ratio [OR], 1.90; 95% CI, 1.54-2.35; P < 0.001), higher baseline IOP (per mmHg: OR, 1.20; 95% CI, 1.12-1.29; P < 0.001) and longer axial length (per mm: OR, 1.22; 95% CI, 1.07-1.40, P = 0.004). CONCLUSION: Six-year incidence of POAG was 1.31% in a multiethnic Asian population. Older age, higher IOP, and longer axial length were associated with higher risk of POAG. These findings can help in future projections and guide public healthcare policy decisions for screening at-risk individuals. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Collagen-related genes influence the glaucoma risk factor, central corneal thickness.

Central corneal thickness (CCT) is a risk factor of glaucoma, the most common cause of irreversible blindness worldwide. The identification of genetic determinants affecting CCT in the normal population will provide insights into the mechanisms underlying the association between CCT and glaucoma, as well as the pathogenesis of glaucoma itself. We conducted two genome-wide association studies for CCT in 5080 individuals drawn from two ethnic populations in Singapore (2538 Indian and 2542 Malays) and identified novel genetic loci significantly associated with CCT (COL8A2 rs96067, p(meta) = 5.40 × 10⁻¹³, interval of RXRA-COL5A1 rs1536478, p(meta) = 3.05 × 10⁻9). We confirmed the involvement of a previously reported gene for CCT and brittle cornea syndrome (ZNF469) [rs9938149 (p(meta) = 1.63 × 10⁻¹6) and rs12447690 (p(meta) = 1.92 × 10⁻¹4)]. Evidence of association exceeding the formal threshold for genome-wide significance was observed at rs7044529, an SNP located within COL5A1 when data from this study (n = 5080, P = 0.0012) were considered together with all published data (reflecting an additional 7349 individuals, p(Fisher) = 1.5 × 10⁻9). These findings implicate the involvement of collagen genes influencing CCT and thus, possibly the pathogenesis of glaucoma.

Association of variants in FRAP1 and PDGFRA with corneal curvature in Asian populations from Singapore.

Corneal curvature (CC) is a key determinant of major eye diseases, such as keratoconus, myopia and corneal astigmatism. No prior studies have discovered the genes for CC. Here we report the findings from four genome-wide association studies of CC in 10 008 samples from three population groups in Singapore. Our discovery phase surveyed 2867 Chinese and 3072 Malays, allowing us to identify two loci that were associated with CC variation: FRAP1 on chromosome 1p36.2 and PDGFRA on chromosome 4q12. These findings were subsequently replicated in a validation study involving an additional 2953 Asian Indians and a further collection of 1116 Chinese children. The effect sizes of the identified variants were consistent across all four cohorts, with seven single nucleotide polymorphisms (SNPs) in FRAP1 (lead SNP: rs17036350, meta P-value = 4.06 × 10(-13)) and six SNPs in PDGFRA (lead SNP: rs2114039, meta P-value = 1.33 × 10(-9)) attaining genome-wide significance in the SNP-based meta-analysis of the four studies. This is the first genome-wide survey of CC variation and we have identified two implicated loci in three genetically diverse Asian populations, suggesting the presence of common genetic etiology across multiple populations.

Genome-wide association studies in Asians confirm the involvement of ATOH7 and TGFBR3, and further identify CARD10 as a novel locus influencing optic disc area.

Damage to the optic nerve (e.g. from glaucoma) has an adverse and often irreversible impact on vision. Earlier studies have suggested that the size of the optic nerve head could be governed by hereditary factors. We conducted a genome-wide association study (GWAS) on 4445 Singaporean individuals (n = 2132 of Indian and n = 2313 of Malay ancestry, respectively), with replication in Rotterdam, the Netherlands (n = 9326 individuals of Caucasian ancestry) using the most widely reported parameter for optic disc traits, the optic disc area. We identified a novel locus on chromosome 22q13.1, CARD10, which strongly associates with optic disc area in both Singaporean cohorts as well as in the Rotterdam Study (RS; rs9607469, per-allele change in optic disc area = 0.051 mm(2); P(meta) = 2.73×10(-12)) and confirmed the association between CDC7/TGFBR3 (lead single nucleotide polymorphism (SNP) rs1192415, P(meta) = 7.57×10(-17)) and ATOH7 (lead SNP rs7916697, P(meta) = 2.00 × 10(-15)) and optic disc area in Asians. This is the first Asian-based GWAS on optic disc area, identifying a novel locus for the optic disc area, but also confirming the results found in Caucasian persons suggesting that there are general genetic determinants applicable to the size of the optic disc across different ethnicities.

Differential associations of myopia with major age-related eye diseases: the Singapore Indian Eye Study.

PURPOSE: To determine the associations of myopia and axial length (AL) with major age-related eye diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR), age-related cataract, and primary open-angle glaucoma (POAG). DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 3400 Indians (75.6% response rate) aged 40 to 84 years in Singapore. METHODS: Refractive error was determined by subjective refraction, and AL was determined by noncontact partial coherence laser interferometry. Age-related macular degeneration and DR were defined from retinal photographs according to the Wisconsin Age-Related Maculopathy Grading System and Airlie House classification system, respectively. Age-related cataract was diagnosed clinically using the Lens Opacity Classification System (LOCS) III system. Glaucoma was defined according to International Society for Geographical and Epidemiological Ophthalmology criteria. MAIN OUTCOME MEASURES: Age-related macular degeneration, DR, age-related cataract, and POAG. RESULTS: Myopic eyes (spherical equivalent [SE] <-0.5 diopter [D]) were less likely to have AMD (early plus late AMD) (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.25-0.79) or DR (OR, 0.68; 95% CI, 0.46-0.98) compared with emmetropic eyes; each millimeter increase in AL was associated with a lower prevalence of AMD (OR, 0.76; 95% CI, 0.65-0.89) and DR (OR, 0.73; 95% CI, 0.63-0.86). Myopic eyes were more likely to have nuclear (OR, 1.57; 95% CI, 1.13-2.20) and posterior subcapsular (OR, 1.73; 95% CI, 1.10-2.72) cataract, but not cortical cataract (P = 0.64); each millimeter increase in AL was associated with a higher prevalence of posterior subcapsular cataract (PSC) (OR, 1.29; 95% CI, 1.07-1.55), but not nuclear (P = 0.77) or cortical (P = 0.39) cataract. Eyes with high myopia (SE <-6.0 D) were more likely to have POAG (OR, 5.90; 95% CI, 2.68-12.97); each millimeter increase in AL was associated with a higher prevalence of POAG (OR, 1.43; 95% CI, 1.13-1.80). CONCLUSIONS: Myopic eyes are less likely to have AMD and DR but more likely to have nuclear cataract, PSC, and POAG. The associations of myopia with AMD, DR, and POAG are mostly explained by longer AL. However, the association between myopia and nuclear cataract is explained by lens refraction rather than AL.

Use of artificial intelligence in forecasting glaucoma progression.

Artificial intelligence (AI) has been widely used in ophthalmology for disease detection and monitoring progression. For glaucoma research, AI has been used to understand progression patterns and forecast disease trajectory based on analysis of clinical and imaging data. Techniques such as machine learning, natural language processing, and deep learning have been employed for this purpose. The results from studies using AI for forecasting glaucoma progression however vary considerably due to dataset constraints, lack of a standard progression definition and differences in methodology and approach. While glaucoma detection and screening have been the focus of most research that has been published in the last few years, in this narrative review we focus on studies that specifically address glaucoma progression. We also summarize the current evidence, highlight studies that have translational potential, and provide suggestions on how future research that addresses glaucoma progression can be improved.

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.

Prevalence and risk factors of diabetic retinopathy in migrant Indians in an urbanized society in Asia: the Singapore Indian eye study.

PURPOSE: To describe the prevalence of and risk factors for diabetic retinopathy (DR) in Indian persons living in a newly urbanized society in Asia. DESIGN: Population-based study. PARTICIPANTS: Ethnic Indians aged ≥40 years living in Singapore. METHODS: The Singapore Indian Eye Study was conducted between 2007 and 2009. All participants underwent an extensive ophthalmic examination, including retinal photographs obtained after pupil dilation. These images were graded for the presence and severity of DR using the modified Airlie House classification system. Diabetes was defined as hemoglobin A1c level of ≥6.5%, use of diabetic medication, or a physician diagnosis of diabetes. Risk factors were measured using questionnaires, clinical assessments, or laboratory tests. MAIN OUTCOME MEASURES: Any DR, diabetic macular edema (DME), or vision-threatening DR (VTDR). RESULTS: Among the 3400 participants, the age-standardized prevalence was 33.6% (95% confidence interval [CI], 31.4-35.8) for diabetes and 10.5% (95% CI, 9.3-11.8) for DR. Among those with diabetes only, the age-standardized prevalence was 30.4% (95% CI, 26.5-34.8) for any DR, 7.2% (95% CI, 5.3-9.7) for DME, and 7.1% (95% CI, 5.4-9.5) for VTDR. In multivariate analysis, independent risk factors for any DR were younger age (odds ratio [OR], 0.98; 95% CI, 0.96-1.00, per year increase), longer diabetes duration (OR, 1.09; 95% CI, 1.07-1.11 per year increase), higher hemoglobin A1c (OR, 1.23; 95% CI, 1.13-1.34 per percent increase), higher systolic blood pressure (OR, 1.01; 95% CI, 1.00-1.02 per 1-mmHg increase), lower diastolic blood pressure (OR, 0.97; 95% CI, 0.96-0.99 per 1-mmHg increase), history of previous stroke (OR, 2.16; 95% CI, 1.12-4.16), and insulin treatment (OR, 2.99; 95% CI, 1.84-4.87). Similar independent risk factors, except for blood pressure, were found for VTDR. Additionally, persons with lower income and living in smaller houses were associated with VTDR. CONCLUSIONS: One in 3 migrant Indians living in newly urbanized Asian societies have diabetes and 1 in 10 has DR. This is similar to rates reported in Western populations and significantly higher than those reported in India.

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.

Prevalence and causes of visual impairment and blindness in an urban Indian population: the Singapore Indian Eye Study.

PURPOSE: To describe the prevalence and causes of visual impairment and blindness in an urban Indian population. DESIGN: Population-based study. PARTICIPANTS: Ethnic Indians aged more than 40 years living in Singapore. METHODS: Participants underwent standardized ophthalmic assessments for visual impairment and blindness, defined using best-corrected visual acuity (BCVA) and presenting visual acuity (PVA), according to US and modified World Health Organization (WHO) definitions. MAIN OUTCOME MEASURES: Unilateral visual impairment or blindness was defined on the basis of the worse eye, and bilateral visual impairment or blindness was defined on the basis of the better eye. Primary causes of visual impairment were determined. RESULTS: A total of 3400 eligible individuals (75.6% response rate) participated. On the basis of US definitions, the age-standardized prevalence was 0.4% for bilateral blindness (≤20/200, better eye) and 3.4% for bilateral visual impairment (<20/40 to >20/200, better eye). Another 0.3% of bilateral blindness and 13.4% of bilateral visual impairment were correctable with refraction. Cataract was the principal cause of best-corrected bilateral blindness (60.0%) and bilateral visual impairment (65.7%). Other major causes of blindness and visual impairment included diabetic retinopathy, age-related macular degeneration, glaucoma, corneal opacity, and myopic maculopathy. CONCLUSIONS: The prevalence of bilateral blindness and visual impairment in Indians living in Singapore is lower than estimates from populations living in India, but similar to estimates obtained from Singapore Malay and Chinese populations. Cataract is the leading cause of blindness and visual impairment. One in 20 cases of bilateral blindness and 1 in 10 cases of bilateral visual impairment are attributable to diabetic retinopathy. These data may have relevance to many ethnic Indian persons living outside India.

Herpes zoster ophthalmicus.

OPINION STATEMENT: The management of herpes zoster (HZ) usually involves a multidisciplinary approach aiming to reduce complications and morbidity. Patients with herpes zoster ophthalmicus (HZO) are referred to ophthalmologists for prevention or treatment of its potential complications. Without prompt detection and treatment, HZO can lead to substantial visual disability. In our practice, we usually evaluate patients with HZO for corneal complications such as epithelial, stromal, and disciform keratitis; anterior uveitis; necrotizing retinitis; and cranial nerve palsies in relation to the eye. These are acute and usually sight-threatening. We recommend oral acyclovir in conjunction with topical 3% acyclovir ointment, lubricants, and steroids for conjunctival, corneal, and uveal inflammation associated with HZO. Persistent vasculitis and neuritis may result in chronic ocular complications, the most important of which are neurotrophic keratitis, mucus plaque keratitis, and lipid degeneration of corneal scars. Postherpetic complications, especially postherpetic neuralgia (PHN), are observed in well over half of patients with HZO. The severe, debilitating, chronic pain of PHN is treated locally with cold compresses and lidocaine cream (5%). These patients also receive systemic treatment with NSAIDs, and our medical colleagues cooperate in managing their depression and excruciating pain. Pain is the predominant symptom in all phases of HZ disease, being reported by up to 90% of patients. Ocular surgery for HZO-related complications is performed only after adequately stabilizing pre-existing ocular inflammation, raised intraocular pressure, dry eye, neurotrophic keratitis, and lagophthalmos. Cranial nerve palsies are common and most often involve the facial nerve, although palsy of the oculomotor, trochlear, and abducens nerves may occur in isolation or (rarely) simultaneously. In our setting, complete ophthalmoplegia is seen more often than isolated palsies, but recovery is usually complete. Vasculitis within the orbital apex (orbital apex syndrome) or brainstem dysfunction is postulated to be the cause of cranial nerve palsies. A vaccine of a lyophilized preparation of the oka strain of live, attenuated varicella-zoster virus is suggested for patients who are at risk of developing HZ and has been shown to boost immunity against HZ virus in older patients.

Referenced scans improve the repeatability of optical coherence tomography angiography measurements in normal and glaucoma eyes.

AIM: To compare the repeatability of peripapillary perfusion density and flux index measurements on referenced and non-referenced optical microangiography (OMAG) scans in normal, glaucoma suspect and glaucoma eyes. METHODS: In a cross-sectional study, 48 eyes (33 subjects) underwent three repeat, non-referenced peripapillary OMAG scans in the same session and 43 eyes (25 subjects) underwent three referenced peripapillary OMAG scans. In the referenced scan group, repeat scans (second and the third scan) were acquired exactly on the baseline (first) scan using the 'track to prior scan' option on the device. Repeatability estimates of the mean and four-sector (temporal, superior, nasal and inferior) OMAG measurements on the non-referenced and referenced scans were assessed using within-subject coefficient of repeatability (CRw) and variation (CVw). RESULTS: CRw (%) of peripapillary perfusion density measurements (range: 2.0-4.1) on non-referenced scans were significantly higher than that on referenced scans (range: 1.4-2.7). CVw (%) on non-referenced and referenced scans ranged from 1.7 to 3.1 and from 1.2 to 2.1, respectively . CRw of flux index on non-referenced and referenced scans ranged from 4.4 to 5.8 and from 3.6 to 4.8, respectively. CVw on non-referenced and referenced scans ranged from 4.1 to 5.2 and from 3.3 to 4.5, respectively. CONCLUSIONS: Repeatability estimates of OMAG measurements were better on referenced scans compared with non-referenced scans. Perfusion density measurements had lower variability than flux index. OCTA-measured perfusion density of referenced scans is preferable for monitoring vascular change in glaucoma.

Novel association of smaller anterior chamber width with angle closure in Singaporeans.

PURPOSE: To describe variations in anterior chamber width (ACW) and investigate its association with the presence of narrow angles. DESIGN: Cross-sectional study. PARTICIPANTS: We recruited 2047 subjects aged 50 years or more from a community polyclinic and 111 subjects with primary angle closure (PAC) or primary angle closure glaucoma (PACG) from an eye hospital in Singapore. METHODS: All participants underwent gonioscopy, anterior chamber depth (ACD) and axial length (AL) measurement (IOLMaster; Carl Zeiss, Jena, Germany), and anterior-segment optical coherence tomography (AS-OCT, Visante, Carl Zeiss Meditec, Dublin, CA). Customized software was used to measure the ACW, defined as the distance between the scleral spurs in the horizontal (nasal-temporal) axis of AS-OCT scans. An eye was deemed to have narrow angles if the posterior trabecular meshwork was not visible for at least 180 degrees on non-indentation gonioscopy with the eye in the primary position. MAIN OUTCOME MEASURES: Anterior chamber width and narrow angles. RESULTS: Data on 1465 community-based subjects were available for analysis. Anterior chamber width was significantly smaller in women compared with men (11.70 mm vs. 11.81 mm, respectively, P<0.001) and decreased significantly with age (P for trend <0.001). Significant predictors of smaller ACW were lower educational level, lower body mass index, shorter AL, shallower ACD, and Chinese race. Of the 1465 subjects, 315 (21.5%) had narrow angles on gonioscopy. Mean ACW was smaller in eyes with narrow angles compared with those without narrow angles (11.60 mm vs. 11.80 mm, P<0.001). The age- and gender-adjusted odds ratio for the highest quartile compared with the lower 3 quartiles of ACW with the presence of narrow angles was 3.4 (95% confidence interval, 2.3-5.0; P for trend <0.001). Hospital-based subjects with PAC/PACG had even smaller ACW than community subjects with narrow angles (11.33 mm vs. 11.60 mm, P<0.001). CONCLUSIONS: In this cross-sectional study, ACW was smaller in women, Chinese persons, and older persons, and was associated with narrow angles in 2 different study populations. These data suggest that a smaller ACW may represent a novel risk indicator for angle closure.

Quantitative iris parameters and association with narrow angles.

PURPOSE: To investigate the relationship between quantitative iris parameters (iris curvature [I-Curv], iris area [I-Area], and iris thickness) and the presence of narrow angles. DESIGN: Cross-sectional, community-based study. PARTICIPANTS: We recruited 2047 subjects >50 years old without ophthalmic symptoms from a community clinic in Singapore. METHODS: All subjects underwent gonioscopy and anterior segment optical coherence tomography (AS-OCT) under dark conditions. An eye was considered to have narrow angles if the posterior pigmented trabecular meshwork was not visible for >/=180 degrees on nonindentation gonioscopy with the eye in the primary position. Customized software was used on horizontal AS-OCT scans to measure I-Curv, I-Area, and iris thickness 750 mum (IT750) and 2000 mum (IT2000) from the scleral spur. The average of both temporal and nasal measured values of the right eye was used for analysis. MAIN OUTCOME MEASURES: The association between iris parameters and narrow angles on gonioscopy. RESULTS: Iris parameters from 1465 eyes (71.6%) were available for analysis. Of these, 315 subjects (21.5%) had narrow angles. The mean I-Curv (0.366 vs 0.259 mm; P<0.020), IT750 (0.476 vs 0.453 mm; P<0.001), and IT2000 (0.491 vs 0.482 mm; P = 0.010) were greater in persons with than without narrow angles. After adjusting for age, gender, anterior chamber depth, axial length, and pupil size, the greater I-Curv, I-Area, IT750, and IT2000 were significantly associated with narrow angles (odds ratio [OR] 2.5 and 95% confidence interval [CI], 1.3-5.1; OR, 2.7 and 95% CI, 1.6-4.8; OR, 2.6 and 95% CI, 1.6-4.1; OR, 2.7 and 95% CI, 1.5-4.7, comparing 4th with 1st quartile for each parameter, respectively). In stratified analysis, women and subjects aged >/=60 years had stronger associations for most iris parameters with narrow angles than men and younger subjects. CONCLUSIONS: Quantitative iris parameters (I-Curv, I-Area, and iris thickness) are independently associated with narrow angles, particularly in women and older subjects. These data provide further insights into the pathogenesis of angle closure in Singaporeans. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

A Comparison of the Visual Field Parameters of SITA Faster and SITA Standard Strategies in Glaucoma.

PURPOSE: To compare the visual field (VF) parameters of the new Swedish Interactive Thresholding Algorithm (SITA), SITA Faster (SFR) with that of SITA Standard (SS) on the Humphrey Field Analyzer. METHODS: Ninety-seven eyes of 97 subjects (63 glaucoma, 26 glaucoma suspects, and 8 normal eyes) underwent VF examination with SFR and SS strategies on the same day in random order. Agreement in VF parameters between SFR and SS strategies was assessed by Bland and Altman plots. In addition, some subjects underwent a second VF examination with SFR strategy to evaluate its test-retest variability. RESULTS: The median test duration of SS strategy was 6 minutes 14 seconds, whereas SFR was 2 minutes 49 seconds (55% shorter, P<0.001). Median mean deviation (-7.3 vs. -7.6 dB, P=0.73) and VF index (88 vs. 88%, P=0.32) were similar between the 2 strategies, whereas pattern standard deviation was significantly higher (4.8 vs. 4.7 dB, P=0.01) with SS strategy. Overall average threshold sensitivity and Garway-Heath sector-wise threshold sensitivities were similar between the 2 strategies except for the nasal sector where SFR strategy had higher sensitivity (26 vs. 25 dB, P=0.02). Bland-Altman plots showed the mean difference in all VF parameters between the SS and SFR strategies were small (ranging from -1.0 dB for the nasal sector to -0.01 dB for superotemporal sector sensitivity). The test-retest variability of VF parameters with SFR strategy was low. CONCLUSIONS: VF parameters with SFR showed good agreement with that of SS strategy. This, combined with low test-retest variability, suggests that SFR can be considered for diagnosis and monitoring of glaucoma.

Prevalence of plateau iris in primary angle closure suspects an ultrasound biomicroscopy study.

PURPOSE: To determine the prevalence of plateau iris in a cohort of primary angle closure suspects (PACSs) using ultrasound biomicroscopy (UBM). DESIGN: Cross-sectional observational study. PARTICIPANTS: Subjects over the age of 50 years diagnosed as PACSs. INTERVENTION: Subjects were randomized to undergo laser peripheral iridotomy (LPI) in one eye. Ultrasound biomicroscopy was performed before and a week after LPI. MAIN OUTCOME MEASURES: Ultrasound biomicroscopy images were qualitatively assessed using standardized criteria. Plateau iris was defined in a quadrant by the presence of an anteriorly directed ciliary body, an absent ciliary sulcus, a steep iris root from its point of insertion followed by a downward angulation from the corneoscleral wall, presence of a central flat iris plane, and irido-angle contact. At least 2 quadrants had to fulfil the above criteria for an eye to be defined as plateau iris. RESULTS: Two hundred five subjects were enrolled; UBM images of 167 subjects were available for analysis. Plateau iris was found in 54 of 167 (32.3%) PACS eyes after LPI. Quadrantwise analysis showed that 44 of 167 (26.3%) eyes had plateau iris in 1 quadrant, 36 (21.5%) in 2 quadrants, 16 (9.5%) in 3 quadrants, and 2 (1.2%) in all 4 quadrants. Plateau iris was most commonly observed in the superior and inferior quadrants. CONCLUSIONS: Using standardized UBM criteria, plateau iris was found in about a third of PACS eyes after LPI. Prospective longitudinal studies are required to determine the clinical significance of this finding for the management of PACSs.

Comparison of gonioscopy and anterior segment ocular coherence tomography in detecting angle closure in different quadrants of the anterior chamber angle.

PURPOSE: To compare the performance of gonioscopy and anterior segment (AS) optical coherence tomography (OCT) in detecting angle closure in the different quadrants of the anterior chamber angle (ACA). DESIGN: Cross-sectional observational study. PARTICIPANTS: Five hundred two consecutive subjects more than 50 years of age with no previous ophthalmic problems recruited from a community clinic in Singapore. METHODS: All subjects underwent gonioscopy and AS OCT imaging in the dark. Using gonioscopy, the ACA was graded using the Scheie system by a single examiner masked to AS OCT findings. MAIN OUTCOME MEASURES: The ACA in a particular quadrant was classified as closed if the posterior trabecular meshwork could not be seen on gonioscopy. A closed ACA on AS OCT imaging was defined by the presence of any contact between the iris and angle wall anterior to the scleral spur. RESULTS: After excluding eyes with poor image quality, a total of 423 right eyes were included in the analysis. A closed angle in at least 1 quadrant was observed in 59% of the eyes by AS OCT and in 33% of the eyes by gonioscopy (P<0.001), with fair agreement between the two methods (kappa = 0.40). The frequency of closed angles by AS OCT and gonioscopy were 48% versus 29% superiorly, 43% versus 22% inferiorly, 18% versus 14% nasally, and 12% versus 20% temporally, respectively. Of the 119 of 1692 quadrants that were closed on gonioscopy but open on AS OCT, a steep iris profile was present in 61 (51%) of 119 quadrants on AS OCT, and of the 276 of 1692 quadrants that were open on gonioscopy but closed on AS OCT, 196 (71%) of 276 quadrants showed short iridoangle contact on AS OCT. CONCLUSIONS: The highest rates of closed angles on gonioscopy and AS OCT images were observed in the superior quadrant. Anterior segment OCT tended to detect more closed ACAs than gonioscopy, particularly in the superior and inferior quadrants. Variations in the iris profile and level of iridoangle contact also may explain some of the differences seen between gonioscopy and AS OCT.