Publications by authors named "Tin Aung"

649 Publications

Evaluation of the diagnostic performance of swept-source anterior segment optical coherence tomography in primary angle closure disease.

Am J Ophthalmol 2021 Jul 17. Epub 2021 Jul 17.

Department of Ophthalmology, University of California, San Francisco, San Francisco, California.; Ophthalmology Section, Surgical Service, San Francisco Veterans Affairs Medical Center, San Francisco, California.. Electronic address:

Purpose: To evaluate the diagnostic performance of swept-source anterior segment optical coherence tomography (SS-OCT) in differentiating primary angle closure diseases (PACD) from control eyes, as well as primary angle closure (PAC) and primary angle closure glaucoma (PACG) from primary angle closure suspect (PACS) eyes.

Design: Multi-center cross-sectional study.

Methods: Chinese patients were classified into control, PACS and PAC/PACG groups. Area under the receiving operating characteristics curve (AUC) from logistic regression models was used to evaluate discriminating ability. Sensitivity and specificity were calculated and performance of the models was validated using an independent dataset.

Results: A total of 2,928 SS-OCT images from 366 eyes of 260 patients were recruited to develop diagnostic models. The validation dataset included 1,176 SS-OCT images from 147 eyes of 143 patients. For distinguishing PACD from control, average anterior chamber depth (ACD_mean) had the highest AUC of 0.94. With a cut-off of 2.2 mm for ACD_mean, the sensitivity and specificity were 90.2% and 85.2% in the training set. For distinguishing PACS from PAC/PACG, a multivariate model had an AUC of 0.83, with sensitivity and specificity of 82.0% and 62.8% in the training set. Validation set confirmed the findings.

Conclusions: Swept-source anterior segment OCT showed excellent diagnostic performance distinguishing PACD from normal eyes and moderate diagnostic ability distinguishing PAC/PACG from PACS. Anterior chamber depth alone may provide a simple and effective way to diagnose PACD from controls. As ACD can be obtained using other more available modalities, this has implications for early diagnosis of PACD.
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http://dx.doi.org/10.1016/j.ajo.2021.06.033DOI Listing
July 2021

Repeatability and Reproducibility of Anterior Chamber Angle Measurement with Swept-Source Optical Coherence Tomography in Patients with Primary Angle Closure Suspect.

Curr Eye Res 2021 Jul 12:1-8. Epub 2021 Jul 12.

Department of Ophthalmology, University of California, San Francisco, California, USA.

: To evaluate the inter- and intra-observer reliability of anterior chamber (AC) angle measurements obtained by swept-source optical coherence tomography (SS-OCT). Forty-eight consecutive patients diagnosed with primary angle closure suspect (PACS) were included. Three masked observers at different training levels (one glaucoma specialist, one ophthalmology resident, and one pre-medical college student) measured 192 SS-OCT images of the PACS patients. One observer (the glaucoma specialist) repeated measurements 1 week later. SS-OCT parameters included: Anterior segment volume, including corneal, AC, and iris volume; anterior segment dimensions, including AC depth and width (ACD, ACW), and lens vault (LV); and angle parameters, including angle opening distance (AOD), angle recess area (ARA), trabecular iris space area (TISA), and the trabecular iris angle (TIA). Intraclass correlation coefficients (ICCs) were used to measure reliability. For inter-observer reproducibility, ICCs of corneal, AC, and iris volumes were 0.952 to 0.998. ICCs of ACD at all axes were above 0.989. ICCs of ACW and LV were smallest in the 90°-270° axis (0.751 and 0.768) but not significantly different from other axes. ARA, TISA, and TIA at all angles had significantly smallest ICCs 250 µm from the scleral spur compared with 500 µm and 750 µm. The ICCs comparing observers with different training levels had similar ranges and followed similar trends. For intra-observer repeatability, the smallest ICC was 0.843. Decreasing AC depth correlated with increased inter-observer reproducibility. We found excellent intra-observer repeatability for all SS-OCT parameters. Angle measurements have more variation among the observers when taken 250 µm from the scleral spur. Shallow AC might lead to more variability for angle parameters. Non-expert observers may be recruited for high-quality image grading with standard training.
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http://dx.doi.org/10.1080/02713683.2021.1942069DOI Listing
July 2021

Association of peripheral anterior synechiae with anterior segment parameters in eyes with primary angle closure glaucoma.

Sci Rep 2021 Jul 6;11(1):13906. Epub 2021 Jul 6.

Singapore National Eye Centre, Singapore, Singapore.

To investigate the association of peripheral anterior synechiae (PAS) with intraocular pressure (IOP) and anterior-segment parameters in subjects with primary angle-closure glaucoma (PACG). A total of 267 subjects with PACG were recruited and underwent gonioscopy and anterior-segment optical coherence tomography (ASOCT). Customized software was used to measure ASOCT parameters, including angle opening distance (AOD750) and trabecular-iris-space-area (TISA750) at 750 µm from the scleral spur, anterior chamber depth, width, area and volume (ACD, ACW, ACA, ACV), iris thickness (IT750), iris area (IAREA), and lens vault (LV). Presenting IOP was defined as the first IOP reading before the initiation of IOP-lowering treatment. The mean age of the 267 subjects was 67.0 ± 8.9 years, 140 (52.4%) were male, and 246 (92.1%) were of Chinese ethnicity. PAS was present in 122 (45.7%) subjects, and was most frequently found in the superior quadrant (79.5%). Subjects with PAS had greater presenting IOP (28.7 ± 12.9 vs 22.4 ± 9.7 mmHg, p < 0.001), narrower AOD750 (p < 0.001), smaller TISA750 (p < 0.001), ACD (p = 0.04), ACA (p = 0.02), ACV (p = 0.01) and larger LV (p = 0.01) compared to PACG eyes without PAS. No significant differences were noted for iris parameters. A multivariate logistic regression analysis showed that higher presenting IOP (β = 0.20, p < 0.001), worse visual field mean deviation (β = - 0.20, p = 0.01) and narrower AOD750 (β = - 0.25, p = 0.03) were the only parameters that significantly correlated with the extent of PAS in clock hours. Almost one-half of the subjects with PACG demonstrated PAS; these eyes were associated with higher presenting IOP, smaller anterior segment dimensions and more severe disease.
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http://dx.doi.org/10.1038/s41598-021-93293-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260708PMC
July 2021

Diagnostic accuracy of swept source optical coherence tomography classification algorithms for detection of gonioscopic angle closure.

Br J Ophthalmol 2021 Jun 30. Epub 2021 Jun 30.

Department of Ophthalmology, National University Singapore Yong Loo Lin School of Medicine, Singapore.

Purpose: To evaluate the performance of swept source optical coherence tomography (SS-OCT) to detect gonioscopic angle closure using different classification algorithms.

Methods: This was a cross-sectional study of 2028 subjects without ophthalmic symptoms recruited from a community-based clinic. All subjects underwent gonioscopy and SS-OCT (Casia, Tomey Corporation, Nagoya, Japan) under dark room conditions. For each eye, 8 out of 128 frames (22.5° interval) were selected to measure anterior chamber parameters namely anterior chamber width, depth, area and volume (ACW, ACD, ACA, and ACV), lens vault (LV), iris curvature (IC), iris thickness (IT) from 750 µm and 2000 µm from the scleral spur, iris area and iris volume. Five diagnostic algorithms-stepwise logistic regression, random forest, multivariate adaptive regression splines, recursive partitioning and Naïve Bayes were evaluated for detection of gonioscopic angle closure (defined as ≥2 closed quadrants). The performance of the horizontal frame was compared with that of other meridians.

Results: Data from 1988 subjects, including 143 (7.2%) with gonioscopic angle closure, were available for analysis. They were divided into two groups: training (1391, 70%) and validation (597, 30%). The best algorithm for detecting gonioscopic angle closure was stepwise logistic regression with an area under the curve of 0.91 (95% CI 0.88 to 0.93) using all parameters, and 0.88 (95% CI 0.82 to 0.93) using only ACA, LV and IC of the horizontal meridian scan.

Conclusions: A stepwise logistic regression model incorporating SS-OCT measurements has a high diagnostic ability to detect gonioscopic angle closure.
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http://dx.doi.org/10.1136/bjophthalmol-2021-319165DOI Listing
June 2021

Development and Validation of a Preference-Based Glaucoma Utility Instrument Using Discrete Choice Experiment.

JAMA Ophthalmol 2021 Jun 24. Epub 2021 Jun 24.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.

Importance: A glaucoma-specific instrument for estimating utilities across the spectrum of glaucoma severity is currently lacking, hindering the assessment of the cost-effectiveness of glaucoma treatments.

Objective: To develop and validate the preference-based Glaucoma Utility Instrument (Glau-U) and to ascertain the association between Glau-U utilities and severity of glaucoma and vision impairment.

Design, Setting, And Participants: This cross-sectional study was conducted in 2 stages at the Singapore National Eye Centre glaucoma clinics. Stage 1 focused on the identification and pretesting of the Glau-U attributes and was carried out between June 2009 and May 2016. Stage 2 involved the development and administration of the discrete choice experiment (DCE) survey and tasks and was conducted between May 7, 2018, and December 11, 2019. Stage 2 participants were English- or Mandarin-speaking Singaporean citizens or permanent residents of Chinese, Malay, or Indian ethnicity who were 40 years or older and had a clinical diagnosis of glaucoma in at least 1 eye.

Exposures: Glau-U comprised 6 quality-of-life attributes: activities of daily living, lighting and glare, movement, eye discomfort, other effects of glaucoma, and social and emotional effects. The descriptions or response options for these attributes were no difficulty or never, some difficulty or sometimes, or severe difficulty or often.

Main Outcomes And Measures: Utility weights for Glau-U were developed using a DCE questionnaire, which was interviewer administered to participants. Mixed logit regression determined utility weights for each health state. Glau-U utility weights across better- or worse-eye glaucoma and vision impairment severity were calculated using 1-way analysis of variance. Correlations between Glau-U utilities and better- or worse-eye visual fields and EuroQol 5-Dimension utilities were ascertained to assess convergent and divergent validity.

Results: Of the 304 participants (mean [SD] age, 68.3 [8.7] years; 182 men [59.9%]), 281 (92.4%) had no vision impairment in the better eye, 13 (4.3%) had mild impairment, and 10 (3.3%) had moderate to severe vision impairment. Mean (SD) Glau-U utilities decreased as better-eye glaucoma severity increased (none: 0.73 [0.21]; mild: 0.66 [0.21]; moderate: 0.66 [0.20]; severe: 0.60 [0.28]; and advanced or end-stage: 0.22 [0.38]; P < .001), representing reductions of 20.7% to 76.1% in quality-adjusted life-years compared with a health state that included preperimetric glaucoma. Mean (SD) Glau-U utilities also decreased as better-eye vision impairment worsened from 0.67 (0.23) for none to 0.58 (0.32) for mild to 0.46 (0.29) for moderate to severe vision impairment. Glau-U utilities demonstrated moderate correlations with better-eye (r = 0.34; P < .001) and worse-eye (r = 0.33; P < .001) mean deviation scores and low correlations with EuroQol 5-Dimension utilities (r = 0.22; P < .001), supporting convergent and divergent validity.

Conclusions And Relevance: Use of Glau-U revealed large decrements in utility that were associated with late-stage glaucoma, suggesting that this new instrument may be useful for cost-effectiveness analyses of interventions and informing resource allocation policies for glaucoma and vision loss.
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http://dx.doi.org/10.1001/jamaophthalmol.2021.1874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227456PMC
June 2021

Describing the Structural Phenotype of the Glaucomatous Optic Nerve Head Using Artificial Intelligence.

Am J Ophthalmol 2021 Jun 19. Epub 2021 Jun 19.

Ophthalmic Engineering & Innovation Laboratory (OEIL), Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Duke-NUS Medical School, Singapore. Electronic address:

Purpose: To develop a novel deep-learning approach that can describe the structural phenotype of the glaucomatous ONH and can be used as a robust glaucoma diagnosis tool.

Design: Retrospective, deep-learning approach diagnosis study.

Method: We trained a deep learning network to segment three neural-tissue and four connective-tissue layers of the ONH. The segmented OCT images were then processed by a customized autoencoder network with an additional parallel branch for binary classification. The encoder part of the autoencoder reduced the segmented OCT images into a low-dimensional latent space (LS); whereas the decoder and the classification branches reconstructed the images and classified them as glaucoma or non-glaucoma, respectively. We performed principal component analysis on the latent parameters and identified the principal components (PCs). Subsequently, the magnitude of each PC was altered in steps and reported how it impacted the morphology of the ONH.

Results: The image reconstruction quality and diagnostic accuracy increased with the size of the LS. With 54 parameters in the LS, the diagnostic accuracy was 92.0±2.3% with a sensitivity of 90.0±2.4% (at 95% specificity), and the corresponding Dice coefficient for the reconstructed images was 0.86±0.04. By changing the magnitudes of PC in steps, we were able to reveal how the morphology of the ONH changes as one transitions from a 'non-glaucoma' to a 'glaucoma' condition.

Conclusions: Our network was able to identify novel biomarkers of the ONH for glaucoma diagnosis. Specifically, the structural features identified by our algorithm were found to be related to clinical observations of glaucoma.
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http://dx.doi.org/10.1016/j.ajo.2021.06.010DOI Listing
June 2021

Population-Based Utility of van Herick Grading for Angle-Closure Detection.

Ophthalmology 2021 Jun 12. Epub 2021 Jun 12.

Department of Ophthalmology, Massachusetts Eye and Ear, Boston, Massachusetts. Electronic address:

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http://dx.doi.org/10.1016/j.ophtha.2021.06.010DOI Listing
June 2021

More than meets the eye: a patient with hand swelling and newly diagnosed Diabetes Mellitus.

Am J Med 2021 Jun 5. Epub 2021 Jun 5.

Department of General Medicine, Sengkang General Hospital, Singapore.

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http://dx.doi.org/10.1016/j.amjmed.2021.05.009DOI Listing
June 2021

Providers preferences towards greater patient health benefit is associated with higher quality of care.

Int J Health Econ Manag 2021 Jun 4. Epub 2021 Jun 4.

Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD, 21205, USA.

Standard theories of health provider behavior suggest that providers are motivated by both profit and an altruistic interest in patient health benefit. Detailed empirical data are seldom available to measure relative preferences between profit and patient health outcomes. Furthermore, it is difficult to empirically assess how these relative preferences affect quality of care. This study uses a unique dataset from rural Myanmar to assess heterogeneous preferences toward treatment efficacy relative to provider profit and the impact of these preferences on the quality of provider diagnosis and treatment. Using conjoint survey data from 187 providers, we estimated the marginal utilities of higher treatment efficacy and of higher profit, and the marginal rate of substitution between these outcomes. We also measured the quality of diagnosis and treatment for malaria among these providers using a previously validated observed patient simulation. There is substantial heterogeneity in providers' utility from treatment efficacy versus utility from higher profits. Higher marginal utility from treatment efficacy is positively associated with the quality of treatment among providers, and higher marginal utility from profit are negatively associated with quality of diagnosis. We found no consistent effect of the ratio of marginal utility of efficacy vs marginal utility of profit on quality of care. Our findings suggest that providers vary in their preferences towards profit and treatment efficacy, with those providers that place greater weight on treatment efficacy providing higher quality of care.
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http://dx.doi.org/10.1007/s10754-021-09298-2DOI Listing
June 2021

The Serum Anion Gap Revisited: A Verified Reference Interval for Contemporary Use.

Intern Med J 2021 May 24. Epub 2021 May 24.

Department of Renal Medicine, Changi General Hospital, Singapore.

Background: The anion gap (AG) is often used to evaluate acid-base disorders. The reference interval for normal AG is used to differentiate between raised (gap) or normal AG (non-gap) acidosis. Historically accepted AG values may not be valid with the evolution of modern analytical techniques and the reference interval requires revalidation.

Aims: To determine the reference interval for AG based on current laboratory techniques.

Methods: During a health-screening exercise, 284 participants with no major illnesses volunteered surplus blood for analysis. The samples were tested in an internationally-accredited clinical laboratory. AG was calculated by (Na ) - (Cl ) - (HCO3 ) and AG by (Na ) + (K ) - (Cl ) - (HCO ). The reference interval was determined at 2.5th-97.5th percentiles. Analysis was further undertaken for a sub-cohort of 156 individuals with no sub-optimal health indicators.

Results: Median age was 35 years, BMI 23.4 kg/m and glomerular filtration rate 106 mL/min/1.73m . Median AG was 13 mmol/L and the reference interval for normal AG is 10-18 mmol/L with a 99% level of confidence. Statistically significant differences in AG were detected for sex, race, obesity and serum albumin but the difference was 1 mmol/L between subgroups. The reference interval was the same for the sub-cohort of 156 individuals. Median AG was 17.7 mmol/L and reference interval was 14.6-22.5 mmol/L.

Conclusions: The AG reference interval of 10-18 mmol/L is valid for laboratories with similar reference intervals for electrolytes. Lower values expected with current laboratory techniques were not observed. The median AG of 13 mmol/L may be used to differentiate gap acidosis, non-gap acidosis or mixed acid-base disorders. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/imj.15396DOI Listing
May 2021

Seroepidemiologic Survey of Crimean-Congo Hemorrhagic Fever Virus in Logging Communities, Myanmar.

Emerg Infect Dis 2021 06;27(6):1709-1713

Crimean-Congo hemorrhagic fever virus (CCHFV) is endemic in Asia, infecting many animal hosts, but CCHFV has not been reported in Myanmar. We conducted a seroepidemiologic survey of logging communities in Myanmar and found CCHFV exposure was common (9.8%) and exposure to wild animal blood and body fluids was associated with seropositivity.
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http://dx.doi.org/10.3201/eid2706.203223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153884PMC
June 2021

Comparing the Safety and Efficacy of Phacogoniosynechialysis With Phacotrabeculectomy in the Management of Refractory Acute Primary Closure Angle Glaucoma With Cataract: A Multicenter Randomized Trial.

J Glaucoma 2021 Jul;30(7):552-558

Vietnam National Eye Hospital.

Prcis: Combined phacoemulsification-goniosynechialysis (phaco-GSL) and unaugmented phacotrabeculectomy were both found to be effective in treating eyes with significant cataract and medically unresponsive acute primary angle closure glaucoma (PACG). Phaco-GSL seemed to be safer, with fewer surgical complications, and achieved better visual acuity than phacotrabeculectomy.

Objectives: To compare the results of combined phaco-GSL with unaugmented phacotrabeculectomy in the management of eyes with medically unresponsive acute PACG and cataract.

Participants And Research Methods: This was a prospective randomized controlled trial involving patients with significant cataract and acute PACG who were not responsive to maximal medical therapy. Three ophthalmic centers in Hanoi, Vietnam, participated in this trial. Study subjects were randomized into 2 groups: phaco-GSL or phacotrabeculectomy. Of note, mitomycin-C or 5-fluorouracil were not used during trabeculectomy, but postoperative bleb needling with 5-fluorouracil injection(s) was allowed. The primary outcome of the study was the rate of postoperative surgical complications in the first 3 months after surgery. The secondary outcome, determined at 1 year, assessed whether treatment was completely successful [defined as intraocular pressure (IOP)<21 mm Hg without IOP-lowering drops], or partially successful (IOP<21 mm Hg with IOP-lowering drops). Treatment failure was defined as IOP≥21 mm Hg with maximal IOP-lowering drops.

Results: In total, 79 eyes from 79 patients (62 females, 17 males) were recruited (42 and 37 eyes in the phaco-GSL and phacotrabeculectomy groups, respectively). There were no statistically significant differences between the 2 groups at baseline in terms of age, visual acuity, IOP, anterior angle width, or preoperative ultrasound biomicroscopy index. Postoperative complications in the first 3 months were seen more frequently in the phacotrabeculectomy group (62.2%) than in the phaco-GSL group (14.3%, P<0.01). At 1 year postsurgery, treatment was 100% successful in both groups, with no difference in the mean IOP (15.38±3.42 vs. 15.72±4.47 mm Hg). The visual field index improved significantly following surgery in both groups, but there was also no significant difference between the 2 groups. However, there was a significant difference in the best corrected visual acuity at 1 year, with patients in the phaco-GSL group achieving better vision (0.45±0.21 logMAR in the phaco-GSL group vs. 0.64±0.27 logMAR in the phacotrabeculectomy group, P=0.04). The mean angle width was also significantly larger in the phaco-GSL group than the phacotrabeculectomy group (2.34±0.33 vs. 1.25±0.41 Shaffer degrees). Similarly, on ultrasound biomicroscopy, the anterior chamber was deeper after 12 months (2.87±0.28 to 2.48±0.33 mm), and the mean trabecular-iris angle area was wider at 12 months (21.88±7.07 vs. 14.95±4.39 degrees) in the phaco-GSL than the phacotrabeculectomy group.

Conclusions: Phaco-GSL and phacotrabeculectomy were both effective in treating medically unresponsive cases of acute PACG with cataracts. However, phaco-GSL showed better visual outcomes, wider drainage angles postsurgery, and fewer complications than phacotrabeculectomy.
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http://dx.doi.org/10.1097/IJG.0000000000001868DOI Listing
July 2021

Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images.

PLoS Genet 2021 May 12;17(5):e1009497. Epub 2021 May 12.

School of Life Course Sciences, Section of Ophthalmology, King's College London, London, United Kingdom.

Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function.
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http://dx.doi.org/10.1371/journal.pgen.1009497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143408PMC
May 2021

Circumferential Assessment of Changes in Anterior Segment Characteristics and Baseline Predictors of Angle Widening after Laser Iridotomy in Caucasian Eyes.

J Glaucoma 2021 Apr 28. Epub 2021 Apr 28.

Singapore Eye Research Institute and Singapore National Eye Centre, Singapore Duke-NUS Medical School, Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Department of Diagnostics and Microsurgery of Glaucoma, Medical University of Lublin, Poland.

Prcis: Laser peripheral iridotomy widened the iridocorneal angle and flattened the iris circumferentially in Caucasian eyes and baseline refractive error, lens vault and iris volume play a significant role in the angle widening.

Purpose: To investigate circumferential angle widening and iris changes after laser peripheral iridotomy (LPI) using swept-source optical coherence tomography (SS-OCT) in Caucasian eyes with the use of novel anterior segment parameters.

Methods: 130 eyes (68 PACS, 34 PAC and 28 PACG eyes) of sixty-six subjects underwent 360-degrees SS-OCT (SS-1000 CASIA, Tomey Corporation, Nagoya, Japan) angle imaging and gonioscopy in the dark before and 7, 30, 90 days after LPI. For each eye, 16 frames (11.25 degree apart) were selected for analysis from 128 cross-sectional images, and novel 2- and 3-dimensional anterior segment parameters namely angle opening distance area (AODA) and the trabecular iris space volume (TISV) 750▒µm from the scleral spur, as well as iris parameters such as iris thickness (IT750 and IT2000), iris curvature (IC) and iris curvature area (ICA) were measured for each image.

Results: AODA and TISV were significantly increased and the IC and ICA were significantly decreased at Day 7, 30 and 90 after LPI when compared to their baseline (all P<0.001) but there was no significant change in the IT750 and IT2000 (all P>0.05). The multivariable linear regression model showed that significant association of ΔAODA with refractive error (β=-0.23, P=0.013), lens vault (β=2.8, P=0.007) and iris volume (β=-0.11, P=0.027) after adjusting for age and gender.

Conclusions: LPI widened the iridocorneal angle and flattened the iris circumferentially in Caucasian eyes in this study. Baseline refractive error, lens vault and iris volume play a significant role in the circumferential angle widening by LPI.
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http://dx.doi.org/10.1097/IJG.0000000000001866DOI Listing
April 2021

The Global Extent of Undetected Glaucoma in Adults: A Systematic Review and Meta-analysis.

Ophthalmology 2021 Apr 16. Epub 2021 Apr 16.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Republic of Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Republic of Singapore. Electronic address:

Topic: Glaucoma is the leading cause of irreversible blindness, despite having good prognosis with early treatment. We evaluated the global extent of undetected glaucoma and the factors associated with it in this systematic review and meta-analysis.

Clinical Relevance: Undetected glaucoma increases the risk of vision impairment, which leads to detrimental effects on the quality-of-life and socioeconomic well-being of those affected. Detailed information on the extent and factors associated with undetected glaucoma aid in the development of public health interventions.

Methods: We conducted a systematic review and meta-analysis of population-based studies published between January 1, 1990, and June 1, 2020. Article search was conducted in online databases (PubMED, Web-of-Science), grey literatures (OpenGrey), and nongovernment organization reports. Our outcome measure was the proportion of glaucoma cases that were undetected previously. Manifest glaucoma included any form of glaucoma reported in the original studies and may include primary open-angle glaucoma (POAG), primary angle-closure-glaucoma, secondary glaucoma, or a combination thereof. Undetected glaucoma was defined as glaucoma cases that were undetected prior to diagnosis in the respective study. Random-effect meta-analysis was used to estimate the pooled proportion of undetected glaucoma. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Meta-analysis of Observational Studies in Epidemiology guidelines in our study.

Results: We identified 61 articles from 55 population-based studies (n = 189 359 participants; n = 6949 manifest glaucoma). Globally, more than half of all glaucoma cases were undetected previously on average in each geographical region. Africa (odds ratio [OR], 12.70; 95% confidence interval [CI], 4.91-32.86) and Asia (OR, 3.41; 95% CI, 1.63-7.16) showed higher odds of undetected glaucoma as compared with Europe. Countries with low Human Development Index (HDI; <0.55) showed a higher proportion of undetected manifest glaucoma as compared with countries of medium to very high HDI (≥0.55; all P < 0.001). In 2020, 43.78 million POAG cases were projected to be undetected, of which 76.7% were in Africa and Asia.

Discussion: Undetected glaucoma is highly prevalent across diverse communities worldwide and more common in Africa and Asia. Strategies to improve detection are needed to prevent excess visual disability and blindness resulting from glaucoma.
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http://dx.doi.org/10.1016/j.ophtha.2021.04.009DOI Listing
April 2021

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

Br J Ophthalmol 2021 Apr 12. Epub 2021 Apr 12.

Singapore Eye Research Institute/Singapore National Eye Centre, Singapore

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.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318275DOI Listing
April 2021

OCT-GAN: single step shadow and noise removal from optical coherence tomography images of the human optic nerve head.

Biomed Opt Express 2021 Mar 19;12(3):1482-1498. Epub 2021 Feb 19.

Ophthalmic Engineering and Innovation Laboratory (OEIL), Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.

Speckle noise and retinal shadows within OCT B-scans occlude important edges, fine textures and deep tissues, preventing accurate and robust diagnosis by algorithms and clinicians. We developed a single process that successfully removed both noise and retinal shadows from unseen single-frame B-scans within 10.4ms. Mean average gradient magnitude (AGM) for the proposed algorithm was 57.2% higher than current state-of-the-art, while mean peak signal to noise ratio (PSNR), contrast to noise ratio (CNR), and structural similarity index metric (SSIM) increased by 11.1%, 154% and 187% respectively compared to single-frame B-scans. Mean intralayer contrast (ILC) improvement for the retinal nerve fiber layer (RNFL), photoreceptor layer (PR) and retinal pigment epithelium (RPE) layers decreased from 0.362 ± 0.133 to 0.142 ± 0.102, 0.449 ± 0.116 to 0.0904 ± 0.0769, 0.381 ± 0.100 to 0.0590 ± 0.0451 respectively. The proposed algorithm reduces the necessity for long image acquisition times, minimizes expensive hardware requirements and reduces motion artifacts in OCT images.
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http://dx.doi.org/10.1364/BOE.412156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984803PMC
March 2021

Referral for disease-related visual impairment using retinal photograph-based deep learning: a proof-of-concept, model development study.

Lancet Digit Health 2021 01;3(1):e29-e40

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Duke-NUS Medical School, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address:

Background: In current approaches to vision screening in the community, a simple and efficient process is needed to identify individuals who should be referred to tertiary eye care centres for vision loss related to eye diseases. The emergence of deep learning technology offers new opportunities to revolutionise this clinical referral pathway. We aimed to assess the performance of a newly developed deep learning algorithm for detection of disease-related visual impairment.

Methods: In this proof-of-concept study, using retinal fundus images from 15 175 eyes with complete data related to best-corrected visual acuity or pinhole visual acuity from the Singapore Epidemiology of Eye Diseases Study, we first developed a single-modality deep learning algorithm based on retinal photographs alone for detection of any disease-related visual impairment (defined as eyes from patients with major eye diseases and best-corrected visual acuity of <20/40), and moderate or worse disease-related visual impairment (eyes with disease and best-corrected visual acuity of <20/60). After development of the algorithm, we tested it internally, using a new set of 3803 eyes from the Singapore Epidemiology of Eye Diseases Study. We then tested it externally using three population-based studies (the Beijing Eye study [6239 eyes], Central India Eye and Medical study [6526 eyes], and Blue Mountains Eye Study [2002 eyes]), and two clinical studies (the Chinese University of Hong Kong's Sight Threatening Diabetic Retinopathy study [971 eyes] and the Outram Polyclinic Study [1225 eyes]). The algorithm's performance in each dataset was assessed on the basis of the area under the receiver operating characteristic curve (AUC).

Findings: In the internal test dataset, the AUC for detection of any disease-related visual impairment was 94·2% (95% CI 93·0-95·3; sensitivity 90·7% [87·0-93·6]; specificity 86·8% [85·6-87·9]). The AUC for moderate or worse disease-related visual impairment was 93·9% (95% CI 92·2-95·6; sensitivity 94·6% [89·6-97·6]; specificity 81·3% [80·0-82·5]). Across the five external test datasets (16 993 eyes), the algorithm achieved AUCs ranging between 86·6% (83·4-89·7; sensitivity 87·5% [80·7-92·5]; specificity 70·0% [66·7-73·1]) and 93·6% (92·4-94·8; sensitivity 87·8% [84·1-90·9]; specificity 87·1% [86·2-88·0]) for any disease-related visual impairment, and the AUCs for moderate or worse disease-related visual impairment ranged between 85·9% (81·8-90·1; sensitivity 84·7% [73·0-92·8]; specificity 74·4% [71·4-77·2]) and 93·5% (91·7-95·3; sensitivity 90·3% [84·2-94·6]; specificity 84·2% [83·2-85·1]).

Interpretation: This proof-of-concept study shows the potential of a single-modality, function-focused tool in identifying visual impairment related to major eye diseases, providing more timely and pinpointed referral of patients with disease-related visual impairment from the community to tertiary eye hospitals.

Funding: National Medical Research Council, Singapore.
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http://dx.doi.org/10.1016/S2589-7500(20)30271-5DOI Listing
January 2021

The Effect of Medical Lowering of Intraocular Pressure on Peripapillary and Macular Blood Flow as Measured by Optical Coherence Tomography Angiography in Treatment-naive Eyes.

J Glaucoma 2021 Jun;30(6):465-472

Singapore Eye Research Institute, Singapore National Eye Centre.

Prcis: Reduction of intraocular pressure (IOP) by latanoprost in treatment-naive eyes is significantly correlated to an increase in vessel density (VD) at the optic nerve head (ONH).

Purpose: To evaluate the effect of topical latanoprost on ocular microvasculature using optical coherence tomography angiography (OCTA).

Patients And Methods: In this prospective case-control study, 26 eyes from 18 treatment-naive subjects in whom prostaglandin analogue (PGA) latanoprost 0.005% was initiated were included as cases. In 10 out of the 18 subjects, medication was initiated in only 1 eye; their contralateral untreated eyes were used as controls. OCTA (AngioVue, Optovue Inc., Fremont, CA) was performed at baseline and ≥3 weeks after commencing treatment. Main outcome measures were change in flow area and VD at the ONH, radial peripapillary capillaries (RPC), and macula. Comparison between the 2 visits was performed using a linear mixed model adjusted for intereye correlation and mean ocular perfusion pressure.

Results: IOP decreased by 26.1%±11.3% (P<0.001) in the cases and 0.18%±12.2% (P=0.63) in controls. Significant correlations between change in IOP and change in ONH VD (correlation coefficient [r]=-0.42, P=0.04), and between change in IOP and change in RPC VD (r=-0.48, P=0.02) were observed in the cases, whereas none were observed in the controls. When multiple testing was considered, no significant changes in flow area and VD were observed in cases and controls.

Conclusions: The reduction of IOP by a PGA in treatment-naive eyes was significantly correlated to the increase in ONH VD and RPC VD. This may indicate a mechanism by which IOP reduction modulates the risk of glaucoma progression by improving ocular microperfusion.
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http://dx.doi.org/10.1097/IJG.0000000000001828DOI Listing
June 2021

Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries.

Nat Commun 2021 02 24;12(1):1258. Epub 2021 Feb 24.

Faculty of Medicine, University of Southampton, Southampton, UK.

Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.
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http://dx.doi.org/10.1038/s41467-020-20851-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904932PMC
February 2021

Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye.

JAMA 2021 02;325(8):753-764

Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.

Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness.

Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function.

Design, Setting, And Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome.

Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function.

Main Outcomes And Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses.

Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome.

Conclusions And Relevance: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.
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http://dx.doi.org/10.1001/jama.2021.0507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903258PMC
February 2021

Altered Iris Aquaporin Expression and Aqueous Humor Osmolality in Glaucoma.

Invest Ophthalmol Vis Sci 2021 02;62(2):34

Singapore National Eye Centre, Singapore.

Purpose: Aquaporins (AQPs) facilitate transmembrane osmotic water transport and may play a role in iris fluid conductivity, which is implicated in the pathophysiology of glaucoma. In this study, we compared the iris expression of AQPs and aqueous osmolality between primary angle closure glaucoma (PACG), primary open-angle glaucoma (POAG), and nonglaucoma eyes.

Methods: AQP1-5 transcripts from a cohort of 36 PACG, 34 POAG and 26 nonglaucoma irises were measured by quantitative real-time PCR. Osmolality of aqueous humor from another cohort of 49 PACG, 50 POAG, and 50 nonglaucoma eyes were measured using an osmometer. The localization of AQP1 in both glaucoma and nonglaucoma irises was determined by immunofluorescent analysis.

Results: Of the five AQP genes evaluated, AQP1 and AQP2 transcripts were significantly upregulated in both PACG (3.48- and 8.07-fold, respectively) and POAG (3.12- and 11.58-fold, respectively) irises relative to nonglaucoma counterparts. The aqueous osmolalities of PACG (303.68 mmol/kg) and POAG (300.79 mmol/kg) eyes were significantly lower compared to nonglaucoma eyes (312.6 mmol/kg). There was no significant difference in expression of AQP transcripts or aqueous osmolality between PACG and POAG eyes.

Conclusions: PACG and POAG eyes featured significant increase in AQP1 and AQP2 expression in the iris and reduced aqueous osmolality compared to nonglaucoma eyes. These findings suggest that the iris may be involved in altered aqueous humor dynamics in glaucoma pathophysiology. Because PACG did not differ from POAG in both properties studied, it is likely that they are common to glaucoma disease in general.
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http://dx.doi.org/10.1167/iovs.62.2.34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910645PMC
February 2021

Utilisation of poor-quality optical coherence tomography scans: adjustment algorithm from the Singapore Epidemiology of Eye Diseases (SEED) study.

Br J Ophthalmol 2021 Feb 15. Epub 2021 Feb 15.

Singapore Eye Research Institute, Singapore

Purpose: To evaluate the effect of signal strength (SS) on optical coherence tomography (OCT) parameters, and devise an algorithm to adjust the effect, when acceptable SS cannot be obtained.

Methods: 5085 individuals (9582 eyes), aged ≥40 years from the Singapore Epidemiology of Eye Diseases population-based study were included. Everyone underwent a standardised ocular examination and imaging with Cirrus HD-OCT. Effect of SS was evaluated using multiple structural breaks linear mixed-effect models. Expected change for increment in SS between 4 and 10 for individual parameter was calculated. Subsequently we devised and evaluated an algorithm to adjust OCT parameters to higher SS.

Results: Average retinal nerve fibre layer (RNFL) thickness showed shift of 4.11 µm from SS of 5 to 6. Above 6, it increased by 1.72 and 3.35 µm to 7 and 8; and by 1.09 µm (per unit increase) above 8 SS. Average ganglion cell-inner plexiform layer (GCIPL) thickness shifted 5.15 µm from SS of 5 to 6. Above 6, increased by 0.94 µm from 7 to 8; and by 0.16 µm (per unit increase) above 8 SS. When compared with reference in an independent test set, the algorithm produced less systemic bias. Algorithm-adjusted average RNFL was 0.549 µm thinner than the reference, while the unadjusted one was 2.841 µm thinner (p<0.001). Algorithm-adjusted and unadjusted average GCIPL was 1.102 µm and 2.228 µm thinner (p<0.001).

Conclusions: OCT parameters can be adjusted for poor SS using an algorithm. This can potentially assist in diagnosis and monitoring of glaucoma when scans with acceptable SS cannot be acquired from patients in clinics.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317756DOI Listing
February 2021

Anatomic Changes and Predictors of Angle Widening after Laser Peripheral Iridotomy: The Zhongshan Angle Closure Prevention Trial.

Ophthalmology 2021 Aug 23;128(8):1161-1168. Epub 2021 Jan 23.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, People's Republic of China.

Purpose: To assess anatomic changes after laser peripheral iridotomy (LPI) and predictors of angle widening based on anterior segment (AS) OCT and angle opening based on gonioscopy.

Design: Prospective observational study.

Participants: Primary angle-closure suspects (PACSs) 50 to 70 years of age.

Methods: Participants of the Zhongshan Angle Closure Prevention (ZAP) Trial underwent gonioscopy and AS-OCT imaging at baseline and 2 weeks after LPI. Primary angle-closure suspect was defined as the inability to visualize pigmented trabecular meshwork in 2 or more quadrants on static gonioscopy. Laser peripheral iridotomy was performed on 1 eye per patient in superior (between 11 and 1 o'clock) or temporal or nasal locations (at or below 10:30 or 1:30 o'clock). Biometric parameters in horizontal and vertical AS-OCT scans were measured and averaged. Linear and logistic regression modeling were performed to determine predictors of angle widening, defined as change in mean angle opening distance measured at 750 μm from the scleral spur (AOD); poor angle widening, defined as the lowest quintile of change in mean AOD; and poor angle opening, defined as residual PACS after LPI based on gonioscopy.

Main Outcome Measures: Anatomic changes and predictors of angle widening and opening after LPI.

Results: Four hundred fifty-four patients were included in the analysis. Two hundred nineteen underwent superior LPI and 235 underwent temporal or nasal LPI. Significant changes were found among most biometric parameters (P < 0.006) after LPI, including greater AOD (P < 0.001). One hundred twenty eyes (26.4%) showed residual PACS after LPI. In multivariate regression analysis, superior LPI location (P = 0.004), smaller AOD (P < 0.001), and greater iris curvature (P < 0.001), were predictive of greater angle widening. Temporal or nasal LPI locations (odds ratio [OR], 2.60, P < 0.001) was predictive of poor angle widening. Smaller mean gonioscopy grade (OR, 0.34, 1-grade increment) was predictive of poor angle opening.

Conclusions: Superior LPI location results in significantly greater angle widening compared with temporal or nasal locations in a Chinese population with PACS. This supports consideration of superior LPI locations to optimize anatomic changes after LPI.
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http://dx.doi.org/10.1016/j.ophtha.2021.01.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298586PMC
August 2021

Focal Structure-Function Relationships in Primary Open-Angle Glaucoma Using OCT and OCT-A Measurements.

Invest Ophthalmol Vis Sci 2020 12;61(14):33

SERI-NTU Advanced Ocular Engineering (STANCE), Singapore.

Purpose: To evaluate the focal structure-function associations among visual field (VF) loss, optical coherence tomography angiography (OCT-A) vascular measurements, and optical coherence tomography (OCT) structural measurements in glaucoma.

Methods: In this cross-sectional study, subjects underwent standard automated perimetry, OCT-based nerve fiber thickness measurements, and OCT-A imaging. Mappings of focal VF test locations with OCT and OCT-A measurements were defined using anatomically adjusted nerve fiber trajectories and were studied using multivariate mixed-effects analysis. Segmented regression analysis was used to determine the presence of breakpoints in the structure-function associations.

Results: The study included 119 eyes from 86 Chinese subjects with primary open-angle glaucoma (POAG). VF mean deviation was significantly associated with global capillary perfusion density (β = 0.13 ± 0.08) and global retinal nerve fiber layer thickness (β = 0.09 ± 0.02). Focal capillary density (FCD) was significantly associated with VF losses at 34 VF test locations (66.7% of 24-2 VF), with 24 of the 34 locations being within 20° of retinal eccentricity. Focal nerve layer (FNL) thickness was significantly associated with 16 VF test locations (31.4% of 24-2 VF; eight locations within 20° eccentricity). For VF test locations in the central 10° VF, VF losses below the breakpoint were significantly associated with FCD (slope, 0.89 ± 0.12, P < 0.001), but not with FNL thickness (slope, 0.57 ± 0.39, P = 0.15).

Conclusions: Focal capillary densities were significantly associated with a wider range of visual field losses and in a larger proportion of the visual field compared to nerve fiber thickness.
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http://dx.doi.org/10.1167/iovs.61.14.33DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774057PMC
December 2020

Peripapillary sclera exhibits a v-shaped configuration that is more pronounced in glaucoma eyes.

Br J Ophthalmol 2020 Dec 17. Epub 2020 Dec 17.

Ophthalmic Engineering & Innovation Laboratory, Singapore Eye Research Institute, Singapore

Aims: To compare the shape of the anterior surface of the peripapillary sclera (PPS) between glaucoma and healthy subjects.

Methods: 88 primary open angle glaucoma (POAG), 98 primary angle closure glaucoma (PACG) and 372 age-matched and gender-matched healthy controls were recruited in this study. The optic nerve head of one randomly selected eye of each subject was imaged with spectral domain optical coherence tomography. The shape of the PPS was measured through an angle defined between a line parallel to the nasal anterior PPS boundary and one parallel to the temporal side. A negative value indicated that the PPS followed an inverted v-shaped configuration (peak pointing towards the vitreous), whereas a positive value indicated that it followed a v-shaped configuration.

Results: The mean PPS angle in normal controls (4.56±5.99°) was significantly smaller than that in POAG (6.60±6.37°, p=0.011) and PACG (7.90±6.87°, p<0.001). The v-shaped PPS was significantly associated with older age (β=1.79, p<0.001), poorer best-corrected visual acuity (β=3.31, p=0.047), central corneal thickness (β=-0.28, p=0.001), peripapillary choroidal thickness (β=-0.21, p<0.001) and presence of POAG (β=1.94, p<0.009) and PACG (β=2.96, p<0.001). The v-shaped configuration of the PPS significantly increased by 1.46° (p=0.001) in healthy controls for every 10-year increase in age, but not in glaucoma groups.

Conclusions: The v-shaped configuration of the PPS was more pronounced in glaucoma eyes than in healthy eyes. This posterior bowing of the PPS may have an impact on the biomechanical environment of the optic nerve head.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317900DOI Listing
December 2020

Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract.

Commun Biol 2020 12 11;3(1):755. Epub 2020 Dec 11.

Institute of Molecular and Cell Biology, 138673, Singapore, Singapore.

Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P = 2.8 × 10) with nuclear cataract and identified five new loci associated with this disease: SOX2-OT (rs9842371, P = 1.7 × 10), TMPRSS5 (rs4936279, P = 2.5 × 10), LINC01412 (rs16823886, P = 1.3 × 10), GLTSCR1 (rs1005911, P = 9.8 × 10), and COMMD1 (rs62149908, P = 1.2 × 10). The results suggest a strong link of age-related nuclear cataract with congenital cataract and eye development genes, and the importance of common genetic variants in maintaining crystalline lens integrity in the aging eye.
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http://dx.doi.org/10.1038/s42003-020-01421-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733496PMC
December 2020

Towards label-free 3D segmentation of optical coherence tomography images of the optic nerve head using deep learning.

Biomed Opt Express 2020 Nov 15;11(11):6356-6378. Epub 2020 Oct 15.

Ophthalmic Engineering and Innovation Laboratory (OEIL), Singapore Eye Research Institute, 20 College Road, Singapore 169856, Singapore.

Recently proposed deep learning (DL) algorithms for the segmentation of optical coherence tomography (OCT) images to quantify the morphological changes to the optic nerve head (ONH) tissues during glaucoma have limited clinical adoption due to their device specific nature and the difficulty in preparing manual segmentations (training data). We propose a DL-based 3D segmentation framework that is easily translatable across OCT devices in a label-free manner (i.e. without the need to manually re-segment data for each device). Specifically, we developed 2 sets of DL networks: the 'enhancer' (enhance OCT image quality and harmonize image characteristics from 3 devices) and the 'ONH-Net' (3D segmentation of 6 ONH tissues). We found that only when the 'enhancer' was used to preprocess the OCT images, the 'ONH-Net' trained on any of the 3 devices successfully segmented ONH tissues from the other two unseen devices with high performance (Dice coefficients > 0.92). We demonstrate that is possible to automatically segment OCT images from new devices without ever needing manual segmentation data from them.
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http://dx.doi.org/10.1364/BOE.395934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687952PMC
November 2020

Impact of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on in-hospital mortality in COVID-19 patients: ​a systematic review and meta-analysis.

Singapore Med J 2020 Nov 30. Epub 2020 Nov 30.

Department of Cardiology, Changi General Hospital, Singapore.

Introduction: There are concerns that angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) may worsen outcomes in patients with coronavirus disease 2019 (COVID-19). This systemic review and meta-analysis aimed to study in-hospital mortality in COVID-19 patients who were on ACEI/ARB as compared to those not on ACEI/ARB.

Methods: We search PubMed, EMBASE, clinicaltrials.gov and Google Scholar between 1 January 2020 and 30 May 2020 to identify all studies that evaluated the use of ACEI/ARB and reported the in-hospital mortality outcomes in COVID-19 patients. Nine non-randomised studies were eligible for inclusion in the analysis. The primary outcome studied was in-hospital mortality of COVID-19 patients who were on ACEI/ARB compared with those not on ACEI/ARB.

Results: Of the 8,313 patients in the nine studies, 7,622 (91.7%) were from studies with all-comers, while 691 (8.3%) were from studies with only hypertensive patients. 577 (14.6%) in-hospital deaths were observed out of a total of 3,949 patients with an outcome in the nine studies. Overall, there was no significant difference in in-hospital mortality between patients on ACEI/ARB and those not on ACEI/ARB (odds radio [OR] 1.06, 95% confidence interval [CI] 0.75-1.50; p = 0.73). Further sensitivity analysis in the hypertensive group and all-comers group showed similar results (OR 0.88, 95% CI 0.58-1.32; p = 0.53 and OR 1.85, 95% CI 1.00-3.43; p = 0.05, respectively).

Conclusion: This study found that ACEI/ARB has no significant impact on in-hospital mortality in COVID-19 patients and can be used safely in patients with indications.
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http://dx.doi.org/10.11622/smedj.2020159DOI Listing
November 2020

Painless Aortic Dissection Presenting with Isolated Dysphagia.

Am J Med 2021 04 2;134(4):e285-e286. Epub 2020 Nov 2.

Neurology, Sengkang General Hospital, Singapore.

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http://dx.doi.org/10.1016/j.amjmed.2020.09.041DOI Listing
April 2021
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