ORCID Profile
0000-0002-7351-2774
Current Organisations
Singapore Eye Research Institute
,
National Institutes of Health
,
National Cancer Institute, National Institutes of Health
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Publisher: Springer Science and Business Media LLC
Date: 14-07-2022
DOI: 10.1038/S41588-022-01113-Z
Abstract: The chr12q24.13 locus encoding OAS1–OAS3 antiviral proteins has been associated with coronavirus disease 2019 (COVID-19) susceptibility. Here, we report genetic, functional and clinical insights into this locus in relation to COVID-19 severity. In our analysis of patients of European ( n = 2,249) and African ( n = 835) ancestries with hospitalized versus nonhospitalized COVID-19, the risk of hospitalized disease was associated with a common OAS1 haplotype, which was also associated with reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in a clinical trial with pegIFN-λ1. Bioinformatic analyses and in vitro studies reveal the functional contribution of two associated OAS1 exonic variants comprising the risk haplotype. Derived human-specific alleles rs10774671-A and rs1131454 -A decrease OAS1 protein abundance through allele-specific regulation of splicing and nonsense-mediated decay (NMD). We conclude that decreased OAS1 expression due to a common haplotype contributes to COVID-19 severity. Our results provide insight into molecular mechanisms through which early treatment with interferons could accelerate SARS-CoV-2 clearance and mitigate against severe COVID-19.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 18-10-2016
Abstract: We determine the feasibility of using a dark-adapted chromatic (DAC) perimeter to obtain dark-adapted static and dynamic rod function at multiple retinal locations, and compare these functional parameters between subjects with intermediate age-related macular degeneration (AMD) and normal controls. Perimetric dark-adapted retinal sensitivities for the 505 and 620 nm stimuli across 7 retinal locations within the central 12° were repeatedly measured after exposing to a single photobleach in 22 intermediate AMD subjects and 8 controls. The sensitivities for each stimulus at 20 minutes after bleach and the sensitivity difference between the stimuli were used to determine static rod function. Sensitivities for the 505 nm stimulus at various times within the initial 20 minutes after bleach were used to estimate the rod criterion time to determine rod function dynamics. The static and dynamic rod functional parameters were compared between AMD and control eyes. Compared to the control eyes, AMD eyes had a reduction in retinal sensitivities for the 505 nm (P < 0.001) and 620 nm (P < 0.001) stimuli, a reduction in sensitivity difference (P < 0.001), and an increased in rod criterion time (P < 0.001). Region within the central 6° appeared to be the most defective and AMD eyes with reticular pseudodrusen (RPD) seemed to have worse function than eyes without RPD. It is feasible to use a DAC perimeter to study dark-adapted static and dynamic rod-mediated function at multiple retinal loci. Static and dynamic rod function were abnormal in intermediate AMD and more so in eyes with RPD, particularly within the central 6° retina.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 10-2017
Publisher: BMJ
Date: 09-02-2022
DOI: 10.1136/BJOPHTHALMOL-2021-319739
Abstract: To use optical coherence tomography angiography (OCTA) parameters from both the retinal and choroidal microvasculature to detect the presence and severity of diabetic retinopathy (DR). This is a cross-sectional case–control study. OCTA parameters from retinal vasculature, fovea avascular zone (FAZ) and choriocapillaris were evaluated from 3×3 mm 2 fovea-centred scans. Areas under the receiver operating characteristic (ROC) curve were used to compare the discriminative power on the presence of diabetes mellitus (DM), the presence of DR and need for referral: group 1 (no DM vs DM no DR), group 2 (no DR vs any DR) and group 3 (non-proliferative DR (NPDR) vs proliferative DR (PDR)). 35 eyes from 27 participants with no DM and 132 eyes from 75 with DM were included. DR severity was classified into three groups: no DR group (62 eyes), NPDR (51 eyes), PDR (19 eyes). All retinal vascular parameters, FAZ parameters and choriocapillaris parameters were strongly altered with DR stages (p .01), except for the deep plexus FAZ area (p=0.619). Choriocapillaris parameters allowed to better discriminate between no DM versus DM no DR group compared with retinal parameters (areas under the ROC curve=0.954 vs 0.821, p=0.006). A classification model including retinal and choroidal microvasculature significantly improved the discrimination between DR and no DR compared with each parameter separately (p=0.029). Evaluating OCTA parameters from both the retinal and choroidal microvasculature in 3×3 mm scans improves the discrimination of DM and early DR.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 05-2018
DOI: 10.1167/TVST.7.3.3
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 26-04-2018
Abstract: Although impairment of rod function in the early stages of age-related macular degeneration (AMD) has been well recognized, data on longitudinal changes in rod function at multiple retinal locations remain limited. This study investigated the longitudinal changes in retinotopic rod function in eyes with intermediate AMD (iAMD). Complete ophthalmic examination, multimodal imaging, and scotopic perimetry were performed at baseline and at 12-month follow-up. Perimetric scotopic retinal sensitivities for the 505-nm stimulus were repeatedly measured for 20 minutes after exposing to a single photobleach (∼30%). The rod intercept time (RIT) and retinal sensitivity at seven retinal loci within the central 12° were ascertained. Using the 95% limit of measurement variability derived from the control eyes as a reference, the proportion of test points with a significant change in retinal sensitivity or RIT at follow-up was determined. Twenty iAMD and 6 control eyes were included. Decline in rod function was detected at 12-month follow-up in eyes with iAMD, but not in control eyes. Approximately 25% of test points in iAMD eyes showed a significant increase in RIT compared to 6% of test points with a decrease in RIT over the 12-month period (P < 0.001). Similarly, 40% of test points demonstrated a reduction in retinal sensitivity compared to the 7% of test points with an increase in retinal sensitivity at follow-up (P < 0.001). There are detectable retinotopic changes in rod function over 12 months in iAMD eyes, indicating an ongoing disease progression in rod impairment or loss with time.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 13-08-2018
Abstract: To compare static rod function obtained with and without photobleach in control and intermediate age-related macular degeneration (iAMD) participants with and without subretinal drusenoid deposits (SDD). In this cross-sectional study, retinal sensitivities within the central 24° retina were obtained twice using a dark-adapted chromatic perimeter, both with 505- and 625-nm stimuli. Tests were performed after 30 minutes of dark-adaptation either with or without a preceding photobleach. Multimodal imaging was performed to grade AMD and SDD status, and other retinal changes considered being risk factors for progression to late AMD. The sensitivity difference between both stimuli was used to assess rod function. The average point wise sensitivity difference (PWSD) was compared among the study groups. Twenty-nine control subjects and 20 iAMD without SDD and 17 iAMD with SDD cases were recruited. The average PWSD of the SDD group was significantly reduced (more with photobleach) compared with that of the control (P < 0.001) and no-SDD groups (P < 0.001), but only within the central 8°. The average PWSD of the non-SDD group was also reduced compared with the control group but only for measurements with photobleach (P = 0.020). There was no difference in average PWSD between the presence and absence of hyperreflective foci and/or nascent geographic atrophy in iAMD eyes without SDD (P = 0.60) or with SDD (P = 0.12). iAMD eyes with SDD are associated with worse static rod function compared with eyes without SDD. The greatest abnormality in rods is observed within the central 8° and when tested with a preceding photobleach.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 17-04-2019
Abstract: To evaluate rod function longitudinally in intermediate age-related macular degeneration subjects with reticular pseudodrusen (RPD) and without RPD (AMD). Retinal sensitivities (505 and 625 nm) during dark adaptation, at 14 locations within the central 12° macula were obtained after photobleaching at baseline and 12-month visits. Pointwise sensitivity differences between both stimuli were used to assess static rod function, while rod intercept time (RIT) and rod recovery rate (RRR) were used to evaluate dynamic function. Changes in function over time were compared between groups. A total of 23 controls, 12 AMD, and 13 RPD cases were followed-up. At baseline, the RPD group had significantly worst static and dynamic rod function compared to AMD and control groups. Static function in AMD was similar to controls. Static and dynamic function across the central 12° was consistent in controls however, it was most impaired at 4° compared to 12° eccentricity in disease groups. Over 12 months, no AMD cases progressed clinically and static function in AMD improved (P ≤ 0.04), but remained unchanged in control and RPD groups (P ≥ 0.17). The RRR for control and RPD groups remained stable, while the AMD group deteriorated, but only at 12° (P = 0.02). The RIT was stable in AMD (P = 0.75) and RPD (P = 0.71) groups but improved in the control group (P = 0.002). A decrease in RRR was detected over 12 months at 12° eccentricity in the AMD group. Evaluating changes in rod function requires testing at multiple locations including the peripheral macula.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 28-05-2020
DOI: 10.1167/TVST.9.6.30
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.ORET.2021.02.015
Abstract: To evaluate the long-term effect of subthreshold nanosecond laser (SNL) treatment on progression to late age-related macular degeneration (AMD). Observational extension study of a randomized, sham-controlled trial. Two hundred twelve participants with bilateral large drusen. The Laser Intervention in the Early Stages of AMD (LEAD) study was a 36-month trial where participants were randomized to receive SNL or sham treatment in 1 eye at 6-monthly intervals up to 30 months. After the completion of the LEAD study, the 2 largest recruiting sites offered remaining participants an opportunity to enroll in a 24-month observational extension study. This study thus examined all participants from these 2 sites who were enrolled in the LEAD study at baseline, including the additional observational data. Time to develop late AMD, defined on multimodal imaging, between those randomized the SNL or sham treatment. Overall, no significant difference was found in the rate of progression over a 60-month period in those randomized to the SNL compared with the sham group (adjusted hazard ratio [HR], 0.63 95% confidence interval [CI], 0.36-1.09 P = 0.098), similar to the findings at 36 months in the LEAD Study. However, evidence of treatment effect modification continued to emerge based on the coexistence of reticular pseudodrusen (RPD P = 0.007, adjusted interaction). Namely, progression was slowed significantly with SNL treatment for those without coexistent RPD (adjusted HR, 0.34 95% CI, 0.16-0.71 P = 0.004), but it was not significantly different for those with RPD (adjusted HR, 1.81 95% CI, 0.67-4.88 P = 0.239). A 24-month observational extension study to the LEAD Study confirmed that SNL treatment did not significantly reduce the overall rate of progression to late AMD in a cohort with intermediate AMD. However, the persistence of a potential beneficial treatment effect in those without coexistent RPD over a longer follow-up duration of an additional 24 months without additional treatment is encouraging. These findings provide further justification for future trials to examine the potential value of SNL treatment for slowing progression in intermediate AMD.
Publisher: BMJ
Date: 18-10-2023
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.ORET.2018.06.016
Abstract: Although rod function is known to be severely impaired in eyes with reticular pseudodrusen (RPD), it remains unknown whether this impairment is associated with a total loss of rod function or merely a delay in rod recovery. The purpose of the study was to determine rod functional recovery profiles after prolonged dark adaptation (DA) in eyes with age-related macular degeneration (AMD) and RPD. A cross-sectional, case-series study. Subjects with AMD and RPD. Retinal sensitivity was assessed simultaneously at 14 retinal locations within the central 12° in the study eye of each subject after the eye received approximately 20% bleach. Recovery of retinal sensitivity was monitored at regular intervals up to 30 minutes after bleach. If retinal sensitivity of all test points had not recovered to the rod criterion level (-3.0 log units of stimulus intensity) after 30 minutes of DA, monitoring recovery of retinal sensitivity was extended up to 24 hours of DA. Rod functional recovery profile at each test point. Six AMD cases with RPD were included, aged 69 to 79 years, and visual acuity ranged from 20/20 to 20/25. All cases had a delay in rod functional recovery at many retinal locations, with test points within the central 6° most affected. The recovery rate was variable between retinal loci and between subjects, although RPD were present at all test locations. In 5 cases with stage 3 RPD, rod function recovered at all tested locations, but many locations took hours to do so. The case with stage 4 RPD had locations that failed to recover even after 24 hours of DA. Eyes with AMD and RPD are associated with severe rod dysfunction throughout the macula however, rod function does recover in most cases after an extended DA time. These findings suggest that the delay in rod recovery in eyes with RPD is, in most cases, associated with the impairment rather than the total loss of rod photoreceptor function. Stage 4 RPD may represent a point at which some rod photoreceptors are nonfunctional.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 12-10-2021
Location: United States of America
No related grants have been discovered for Rose Tan.