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1.
Sci Rep ; 9(1): 16714, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31723195

RESUMO

About a quarter of children with new onset of Kawasaki disease (KD) encounter coronary arterial involvement. While KD is known to cause vasculitis of medium-sized vessels, few studies have been done to study the involvement of the microcirculation. We aimed to investigate the association between coronary arterial dilatation and retinal microvasculature in a pilot setting, in order to further study the pathophysiological mechanism of KD from the perspective of small vessels changes. We performed a cross-sectional, observational, hospital-based study on 11 children aged 2 years and above with new-onset KD. Cardiac imaging technicians performed the echocardiographic examinations and recorded right coronary artery (RCA), left coronary artery (LCA) and left anterior descending artery (LAD). Qualified retinal graders reviewed and graded standardised retinal photographs to assess retinal microvascular parameters. Among 11 participants, there were 7 boys and 4 girls. Median and interquartile range of participants' age were 5.92 (3.08) years. After adjusting for age and sex, each unit increase in LAD (mm) was significantly associated with increment of retinal arteriolar tortuosity (4.25 × 10-5 units, 95% Confidence Interval: 1.19, 7.32). Retinal arteriolar geometric changes were associated with LAD dilatation in 11 children with new onset of KD. Our pilot provided proof-of-concept that retinal imaging might be useful for detecting coronary arterial involvement in young children with KD and it needs further investigation.

2.
Invest Ophthalmol Vis Sci ; 60(14): 4830-4837, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31747685

RESUMO

Purpose: We investigate macular perfusion and the systemic and ocular associations in a population-based setting. Methods: In this cross-sectional study, 2018 adults residing in Hong Kong underwent detailed ophthalmic examinations after consenting to participate. Macular perfusion was measured with optical coherence tomography angiography (OCTA) using the split-spectrum amplitude decorrelation angiography algorithm. The parafoveal flow index and vessel area density were quantified using automated custom-built software. Results: Of the 2018 participants, the OCTA measurements were available for 1940, and 1631 (84.1%) had good quality scans. The right eyes of these 1631 participants (43.1% men) were included for final analysis. Mean age was 49.8 years (range, 18-92 years). Mean global macular vessel density was 47.3% and 55.1% for the superficial and deep retinal layers, respectively. In multivariate analysis, lower superficial vessel density remained significantly associated with lower signal strength index (SSI; P < 0.001, standardized ß = 0.607) and male sex (P < 0.001, ß = 0.162), and borderline associated with older age (P = 0.09, ß = -0.045) and longer axial length (AL; P = 0.09, ß = -0.037), while lower deep layer vessel density was significantly associated with lower SSI (P < 0.001, standardized ß = 0.667), longer AL (P < 0.001, ß = -0.097), and higher creatinine (P < 0.001, ß = -0.072). Conclusions: This large population-based study provided normative OCTA data of macular vessel density and demonstrated that a lower superficial retinal vessel density was significantly associated with lower SSI and male sex, while a lower deep layer retinal vessel density was significantly associated with lower SSI, longer AL, and higher level of creatinine. These associations must be considered when interpreting clinical quantitative OCTA data.

4.
Br J Ophthalmol ; 103(11): 1605-1609, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31645330

RESUMO

BACKGROUND/AIM: The relationship between diabetic retinopathy (DR) and cognitive impairment (CI) is unclear due to equivocal findings from cross-sectional studies and a lack of long-term data. In this population-based cohort study, we investigated the longitudinal association between the severity of DR and the incidence of CI. METHODS: 682 participants with diabetes, gradable retinal photographs and no CI at baseline 2004-2011) and complete relevant data at follow-up 2010-2016 from the Singapore Epidemiology of Eye Disease Study were included. CI was assessed using the validated Abbreviated Mental Test (AMT), defined as scores of ≤6 and ≤8 for those with 0-6 and >6 years of formal education, respectively. Six-year incident CI was defined as having no CI at baseline but present at the follow-up visit. RESULTS: Of the 682 included participants, 483 (70.8%) had no DR and 199 (29.2%) had any DR. Of those with DR, 142 (20.8%) had minimal/mild DR and 57 (8.4%) had moderate or worse DR at baseline. At the follow-up visit, 40 (5.9%) participants had incident CI based on AMT. In multivariate analysis compared with participants without DR, those with any DR had more than twofold increased odds of incident CI (OR (95% CI): 2.32 (1.07 to 5.03)). Participants with moderate or worse DR had threefold increased odds of developing CI (3.41 (1.06 to 11.00)), compared with those with no DR. CONCLUSIONS: DR, particularly at the more severe stages, is associated with increased risk of developing CI, independent of vision and other risk factors.

5.
BMC Ophthalmol ; 19(1): 206, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619195

RESUMO

BACKGROUND: Real-world data (RWD) has been a valuable addition to the scientific literature regarding treatment pathways, clinical outcomes and characteristics of patients with retinal diseases in recent years. Registries, observational studies and patient databases are often used for real-world research. However, there is limited information for each data source on the design, consistency, data captured, limitations and usability for assessing research questions. Using a systematic approach, we identified RWD sources for patients with retinal diseases and assessed them for completeness of data relating to different outcomes. METHODS: A systematic literature review was carried out to identify RWD sources for patients with retinal disease. Potentially relevant articles published between 2006 and 2016 were screened following electronic searches in Embase and MEDLINE. Congress and supplementary searches were undertaken to identify RWD sources that may not be referenced in full publications. For each data source, availability and quantity of data on baseline status, clinical outcomes, treatment and management, safety, and patient-reported and economic burden were assessed using a bespoke completeness assessment tool based on International Consortium for Health Outcomes Measurement guidelines for macular degeneration. Completeness of data for each area of interest in each data source was assessed and rated using a 'good-moderate-poor' rating system based on availability and quantity of available data. Each data source was then given an overall score based on its score for each of the 7 areas of interest. RESULTS: A total of 128 RWD sources from 32 countries were identified. Of the identified sources, 64 sources from 16 countries of interest were analyzed. Most of these sources provided information on baseline status and clinical outcomes and treatment, but few collected data on economic and patient-reported burden. Of the RWD sources analyzed, 10 scored highly in the overall completeness assessment, collecting data on most or all of the areas of interest; these sources are considered to be robust data sources for performing ophthalmology real-world studies. CONCLUSIONS: The study provides a comprehensive list of RWD sources for patients with retinal disease, many of which will be useful for conducting real-world studies in the field of ophthalmology.

6.
Cell ; 179(3): 736-749.e15, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31626772

RESUMO

Underrepresentation of Asian genomes has hindered population and medical genetics research on Asians, leading to population disparities in precision medicine. By whole-genome sequencing of 4,810 Singapore Chinese, Malays, and Indians, we found 98.3 million SNPs and small insertions or deletions, over half of which are novel. Population structure analysis demonstrated great representation of Asian genetic diversity by three ethnicities in Singapore and revealed a Malay-related novel ancestry component. Furthermore, demographic inference suggested that Malays split from Chinese ∼24,800 years ago and experienced significant admixture with East Asians ∼1,700 years ago, coinciding with the Austronesian expansion. Additionally, we identified 20 candidate loci for natural selection, 14 of which harbored robust associations with complex traits and diseases. Finally, we show that our data can substantially improve genotype imputation in diverse Asian and Oceanian populations. These results highlight the value of our data as a resource to empower human genetics discovery across broad geographic regions.

7.
Am J Mens Health ; 13(5): 1557988319883766, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31646931

RESUMO

Myopia has been linked to body weight and sedentary status, but the association with quantitatively measured physical fitness in adults has not been examined. Cross-sectional analyses were performed to investigate the association between physical fitness and myopia in 3,669 military men (aged 29.4 years) in Taiwan. The severity of myopia obtained from the left eye was classified as mild (-0.5 to -3.0 diopters; n = 544), moderate -3.1 to -6.0 diopters; n = 563), and high (<-6.0 diopters; n =150); others were defined as nonmyopia (n = 2,412). Aerobic fitness was evaluated by time for a 3000-meter run test, and muscular endurance was evaluated by numbers of 2-min sit-ups and 2-min push-ups. A value of p < .0125 was considered significant. A multiple linear regression analysis was used to determine the relationship. Individuals who were less physically fit had higher risk of myopia. The associations were dose-dependently significant with mild, moderate, and high myopia for 3000-meter running time (ß = 9.64; 95% confidence intervals [3.22, 16.05], ß = 12.41; 95% CI [6.05, 18.76], and ß = 20.87; 95% CI [9.22, 32.51], respectively) after controlling for the potential covariates. There tended to be an inverse association with moderate and high myopia for numbers of 2-min push-ups (ß = -1.38; 95% CI [-2.43, -0.34] and ß = -2.10; 95% CI [- 3.97, -0.22], respectively) and 2-min sit-ups (ß = -0.83; 95% CI [-1.54, -0.12] and ß = -1.29; 95% CI [-2.56, -0.02], respectively), respectively. This study suggested that physical fitness, particularly aerobic fitness of the military males who received regular training, is inversely associated with myopia severity, independent of service specialty, body mass index, and educational level.

8.
JAMA Ophthalmol ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31513266

RESUMO

Importance: A deep learning system (DLS) that could automatically detect glaucomatous optic neuropathy (GON) with high sensitivity and specificity could expedite screening for GON. Objective: To establish a DLS for detection of GON using retinal fundus images and glaucoma diagnosis with convoluted neural networks (GD-CNN) that has the ability to be generalized across populations. Design, Setting, and Participants: In this cross-sectional study, a DLS for the classification of GON was developed for automated classification of GON using retinal fundus images obtained from the Chinese Glaucoma Study Alliance, the Handan Eye Study, and online databases. The researchers selected 241 032 images were selected as the training dataset. The images were entered into the databases on June 9, 2009, obtained on July 11, 2018, and analyses were performed on December 15, 2018. The generalization of the DLS was tested in several validation datasets, which allowed assessment of the DLS in a clinical setting without exclusions, testing against variable image quality based on fundus photographs obtained from websites, evaluation in a population-based study that reflects a natural distribution of patients with glaucoma within the cohort and an additive dataset that has a diverse ethnic distribution. An online learning system was established to transfer the trained and validated DLS to generalize the results with fundus images from new sources. To better understand the DLS decision-making process, a prediction visualization test was performed that identified regions of the fundus images utilized by the DLS for diagnosis. Exposures: Use of a deep learning system. Main Outcomes and Measures: Area under the receiver operating characteristics curve (AUC), sensitivity and specificity for DLS with reference to professional graders. Results: From a total of 274 413 fundus images initially obtained from CGSA, 269 601 images passed initial image quality review and were graded for GON. A total of 241 032 images (definite GON 29 865 [12.4%], probable GON 11 046 [4.6%], unlikely GON 200 121 [83%]) from 68 013 patients were selected using random sampling to train the GD-CNN model. Validation and evaluation of the GD-CNN model was assessed using the remaining 28 569 images from CGSA. The AUC of the GD-CNN model in primary local validation datasets was 0.996 (95% CI, 0.995-0.998), with sensitivity of 96.2% and specificity of 97.7%. The most common reason for both false-negative and false-positive grading by GD-CNN (51 of 119 [46.3%] and 191 of 588 [32.3%]) and manual grading (50 of 113 [44.2%] and 183 of 538 [34.0%]) was pathologic or high myopia. Conclusions and Relevance: Application of GD-CNN to fundus images from different settings and varying image quality demonstrated a high sensitivity, specificity, and generalizability for detecting GON. These findings suggest that automated DLS could enhance current screening programs in a cost-effective and time-efficient manner.

9.
Br J Ophthalmol ; 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31558494

RESUMO

BACKGROUND: To examine the normative profile and determinants of retinal nerve fibre layer (RNFL) symmetry in a non-glaucoma, multiethnic Asian population. METHODS: Chinese, Malay and Indian adults aged ≥40 years were recruited from the Singapore Epidemiology of Eye Diseases study. Participants underwent standardised systemic and ocular examinations. RNFL thickness was obtained using a spectral-domain optical coherence tomography (Cirrus HD-OCT). RNFL symmetry (in %) was calculated based on Pearson correlation coefficient between the RNFL thickness profiles of the right and left eyes. Multivariable linear regression analysis was used to investigate the associations between ocular and systemic factors with RNFL symmetry. RESULTS: 4211 participants (1227 Chinese, 1245 Malays, 1739 Indians) were included. The mean RNFL symmetry was 86.7%±8.5% in Chinese, 84.7%±10.2% in Malays and 84.0%±10.7% in Indians. The fifth percentile limit of RNFL symmetry was 71.2% in Chinese, 65.0% in Malays and 62.0% in Indians. In multivariable analysis adjusting for age, gender, ethnicity, hypertension, diabetes, hyperlipidaemia, intereye absolute differences in intraocular pressure (IOP), axial length and disc area, Malays (ß=-0.9; p=0.03) and Indians (ß=-1.76; p<0.001) were found to have lower RNFL symmetry compared with Chinese. Older age, greater intereye differences in IOP, axial length and disc area were significantly associated with lower RNFL symmetry (all p≤0.003). CONCLUSIONS: In non-glaucoma individuals, intereye RNFL profile is less symmetric in Malays and Indians than that in Chinese. This also suggests that current commercial optical coherence tomography's deployment of a single, universal RNFL symmetry cut-off for glaucoma detection is flawed, and ethnic-specific cut-off is warranted.

10.
Ophthalmol Retina ; 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31444144

RESUMO

PURPOSE: To describe the rate of development and progression of fibrosis and macular atrophy (MA) and their relationship with 1-year visual outcomes in Asian participants with neovascular age-related macular degeneration (nAMD). DESIGN: Review of images collected from a prospectively recruited observational cohort. PARTICIPANTS: Participants with treatment-naïve nAMD. METHODS: All participants underwent multimodality imaging at baseline and month 12 and were treated according to standard of care. Retinal specialists evaluated color fundus photographs fluorescein and indocyanine green angiography images to determine the subtypes according polypoidal choroidal vasculopathy (PCV) and non-PCV subtypes. An independent reading center graded qualitative and quantitative morphologic features on spectral-domain OCT. Fibrosis and MA were determined based on multimodal imaging. MAIN OUTCOME MEASURES: Incidence of fibrosis and MA and their impact on visual outcome at 1 year. RESULTS: We included 93 eyes (48.4% PCV). Between baseline and month 12, visual acuity (VA) improved from 0.81±0.56 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, approximately 20/126) to 0.71±0.61 logMAR (Snellen equivalent, approximately 20/100; P = 0.007), and mean retinal thickness decreased from 471.1 µm to 343.4 µm (P < 0.001). Between baseline and month 12, prevalence of fibrosis and MA increased from 13.0% to 37.8% (P < 0.001) and 9.7% to 17.2% (P = 0.008), respectively. Worse baseline VA and presence of subretinal hyperreflective material (SHRM) at month 12 were associated with worse VA at month 12 after adjusting for multiple factors, whereas PCV subtype was associated with better VA at month 12. At month 12, the predominant composition of SHRM was fibrosis (82.5%). CONCLUSIONS: We describe significant development of fibrosis and MA in Asian nAMD eyes and show that fibrosis is the most important predictor of outcomes. These results highlight the need for therapy beyond anti-vascular endothelial growth factor inhibition to address fibrosis in Asian nAMD.

11.
PLoS One ; 14(8): e0220143, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31415580

RESUMO

PURPOSE: To evaluate the roles of known myopia-associated genetic variants for development of myopic macular degeneration (MMD) in individuals with high myopia (HM), using case-control studies from the Consortium of Refractive Error and Myopia (CREAM). METHODS: A candidate gene approach tested 50 myopia-associated loci for association with HM and MMD, using meta-analyses of case-control studies comprising subjects of European and Asian ancestry aged 30 to 80 years from 10 studies. Fifty loci with the strongest associations with myopia were chosen from a previous published GWAS study. Highly myopic (spherical equivalent [SE] ≤ -5.0 diopters [D]) cases with MMD (N = 348), and two sets of controls were enrolled: (1) the first set included 16,275 emmetropes (SE ≤ -0.5 D); and (2) second set included 898 highly myopic subjects (SE ≤ -5.0 D) without MMD. MMD was classified based on the International photographic classification for pathologic myopia (META-PM). RESULTS: In the first analysis, comprising highly myopic cases with MMD (N = 348) versus emmetropic controls without MMD (N = 16,275), two SNPs were significantly associated with high myopia in adults with HM and MMD: (1) rs10824518 (P = 6.20E-07) in KCNMA1, which is highly expressed in human retinal and scleral tissues; and (2) rs524952 (P = 2.32E-16) near GJD2. In the second analysis, comprising highly myopic cases with MMD (N = 348) versus highly myopic controls without MMD (N = 898), none of the SNPs studied reached Bonferroni-corrected significance. CONCLUSIONS: Of the 50 myopia-associated loci, we did not find any variant specifically associated with MMD, but the KCNMA1 and GJD2 loci were significantly associated with HM in highly myopic subjects with MMD, compared to emmetropes.

12.
Sci Rep ; 9(1): 11751, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409801

RESUMO

Retinal arterioles, venules and capillaries are differentially affected in diabetes, and studying vascular alterations may provide information on pathogenesis of diabetic retinopathy (DR). We conducted a cross-sectional study on 49 diabetic patients, who underwent fundus photography and optical coherence tomographic angiography (OCT-A). Fundus photographs were analysed using semi-automated software for arteriolar and venular parameters, including central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE) and fractal dimension (FD). Capillary parameters were measured using OCT-A, including capillary density index (CDI) and capillary FD of superficial (SVP) and deep (DVP) vascular plexuses. Severe DR was defined as severe non-proliferative DR and proliferative DR. We found that eyes with severe DR had narrower CRAE and sparser SVP CDI than eyes without. In logistic regression analysis, capillary parameters were more associated with severe DR than arteriolar or venular parameters. However, combining arteriolar, venular and capillary parameters provided the strongest association with severe DR. In linear regression analysis, eyes with poorer visual acuity had lower CRAE and FD of arterioles, venules, and DVP capillaries. We concluded that the retinal microvasculature is globally affected in severe DR, reflecting widespread microvascular impairment in perfusion. Arteriolar, venular and capillary parameters provide complementary information in assessment of DR.

13.
Br J Ophthalmol ; 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31401553

RESUMO

BACKGROUND/AIMS: In order to address the eye care needs of the increasing numbers of elderly Chinese globally, there is a need for comprehensive understanding on the longitudinal trends of age-related eye diseases among Chinese. We herein report the key findings from the baseline Singapore Chinese Eye Study (SCES-1), and describe the rationale and methodology of the 6-year follow-up study (SCES-2). METHODS: 3353 Chinese adults who participated in the baseline SCES-1 (2009-2011) were invited for the 6-year follow-up SCES-2 (2015-2017). Examination procedures for SCES-2 included standardised ocular, systemic examinations and questionnaires identical to SCES-1. SCES-2 further included new examinations such as optical coherence tomography angiography, and questionnaires to evaluate health impact and economic burden of eye diseases. RESULTS: In SCES-1, the age-adjusted prevalence of best-corrected low vision (VA<6/12, better-seeing eye) and blindness (VA<6/60, better-seeing eye) were 3.4% and 0.2%, respectively. The prevalence rates for glaucoma, age related macular degeneration, and diabetic retinopathy (among diabetics) were 3.2%, 6.8%, 26.2%, respectively. Of the 3033 eligible individuals from SCES-1, 2661 participated in SCES-2 (response rate=87.7%). Comparing with those who did not attend SCES-2, those attended were younger, had higher SES (all p<0.001), but less likely to be a current smoker, to have diabetes, hypertension, hyperlipidaemia (all p≤0.025). CONCLUSIONS: Building on SCES-1, SCES-2 will be one of the few longitudinal population-based eye studies to report incidence, progression, and risk factors of major age-related eye diseases. Findings from this cohort may offer new insights, and provide useful reference information for other Chinese populations elsewhere.

14.
Ophthalmologica ; : 1-12, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31408872

RESUMO

Diabetes is a global public health disease projected to affect 642 million adults by 2040, with about 75% residing in low- and middle-income countries. Diabetic retinopathy (DR) affects 1 in 3 people with diabetes and remains the leading cause of blindness in working-aged adults. There are 3 broad strategic imperatives to prevent blindness caused by DR. Primary prevention requires preventing or delaying the onset of DR in those with diabetes by systems-level lifestyle modifications such as increasing physical activity or dietary modifications, pharmacological interventions for glycaemic and blood pressure control, and systematic screening for the onset of DR. Secondary prevention requires preventing the progression of DR in patients with DR by continuing systemic risk factor control, regular screening to monitor for the progression of mild DR to vision-threatening stages, and the development and implementation of evidence-based guidelines for managing DR. In this aspect, telemedicine-based DR screening incorporating artificial intelligence technology has the potential to facilitate more widespread and cost-effective screening, particularly in low- and middle-income countries. Tertiary prevention of DR blindness has been the main focus of the clinical ophthalmology community, classically based on laser photocoagulation treatment and ocular surgery but with an increasing use of anti-vascular endothelial growth factor (anti-VEGF) for vision-threatening DR. Evidence from serial epidemiological studies shows blindness due to DR has declined in high-income countries (e.g., the USA and UK) due to coordinated public health education efforts, increased awareness, early detection by DR screening, sustained systemic risk factor control, and the availability of effective tertiary level treatment. However, the progress made in reducing DR blindness in high-income countries may be overwhelmed by the increasing numbers of patients with diabetes and DR in low- and middle-income countries (e.g., China, India, Indonesia, etc.). Thus, to tackle DR at a global level, a paradigm shift in strategic focus from tertiary towards secondary and primary prevention measures with a multi-pronged whole-of-society approach at regional and national levels is urgently needed.

15.
Commun Biol ; 2: 285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396565

RESUMO

Brain lobar volumes are heritable but genetic studies are limited. We performed genome-wide association studies of frontal, occipital, parietal and temporal lobe volumes in 16,016 individuals, and replicated our findings in 8,789 individuals. We identified six genetic loci associated with specific lobar volumes independent of intracranial volume. Two loci, associated with occipital (6q22.32) and temporal lobe volume (12q14.3), were previously reported to associate with intracranial and hippocampal volume, respectively. We identified four loci previously unknown to affect brain volumes: 3q24 for parietal lobe volume, and 1q22, 4p16.3 and 14q23.1 for occipital lobe volume. The associated variants were located in regions enriched for histone modifications (DAAM1 and THBS3), or close to genes causing Mendelian brain-related diseases (ZIC4 and FGFRL1). No genetic overlap between lobar volumes and neurological or psychiatric diseases was observed. Our findings reveal part of the complex genetics underlying brain development and suggest a role for regulatory regions in determining brain volumes.

16.
Am J Ophthalmol ; 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31377279

RESUMO

PURPOSE: The purpose of this study was to investigate whether the addition of primary angle closure glaucoma (PACG) associated genetic loci allows improved detection of PACG, compared to anterior segment parameters measured by imaging. DESIGN: Case-control study METHODS: Genotype data of the 8 PACG SNPs (rs11024102 at PLEKHA7, rs3753841 at COL11A1, rs1015213 located between PCMTD1 and ST18 on Chromosome 8q, rs3816415 at EPDR1, rs1258267 at CHAT, rs736893 at GLIS3, rs7494379 at FERMT2, and rs3739821 mapping in between DPM2 and FAM102A) were available. Customized software was used to measure anterior segment optical coherence tomography (ASOCT) parameters, namely anterior chamber depth, width, and area (ACD, ACW, ACA) and lens vault (LV). Statistical analysis for positive predictive values was modelled using the Receiver operating characteristic curve (AUC). Statistical significance comparing predictive power of the different parameters was calculated using permutation. RESULTS: A total of 388 PACG subjects and 751 controls with both ASOCT and genetic data were available for analysis. Anterior segment parameters including ACD, ACA, and LV had excellent predictive value (AUC) >0.94), except ACW (AUC=0.65) for identifying PACG. The inclusion of genetic risk alleles (either singly or as a composite genetic risk score for 8 GWAS SNPs) to ACD only provided a +0.50% improvement in re-classifying PACG cases and controls over and above the discriminatory value of ACD. This +0.50% improvement was not statistically significant (P>0.05). CONCLUSIONS: Although significant on their own, the incorporation of genetic data in the context of anterior segment imaging parameters like ACD provided only a marginal improvement of PACG detection.

17.
BMJ Open ; 9(Suppl 3): 44-52, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31273015

RESUMO

OBJECTIVES: To describe distributions and concordance of retinal microvasculature measurements in a population-based sample of Australian parent-child dyads at child age 11-12 years. DESIGN: Cross-sectional Child Health CheckPoint study, between waves 6 and 7 of the national population-based Longitudinal Study of Australian Children (LSAC). SETTING: Assessment centres in seven Australian cities, February 2015-March 2016. PARTICIPANTS: Of the 1874 participating families, 1288 children (51% girls) and 1264 parents (87% mothers, mean age 43.7) were analysed. Diabetic participants and non-biological pairs were excluded from concordance analyses. OUTCOME MEASURES: Retinal photographs were taken by non-mydriatic fundus camera. Trained graders scored vascular calibre using semi-automated software, yielding estimates of central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) and arteriolar-venular ratio (AVR). Pearson's correlation coefficients and multivariable linear regression models assessed parent-child concordance. Survey weights and methods accounted for LSAC's complex sampling, stratification and clustering within postcodes. RESULTS: Mean (SD) of CRAE and CRVE were larger in children (159.5 (11.8) and 231.1 (16.5) µm, respectively) than parents (151.5 (14.0) and 220.6 (19.0) µm), yielding similar AVR (children 0.69 (0.05), parents 0.69 (0.06)). Correlation coefficients for parent-child pairs were 0.22 (95% CI 0.16 to 0.27) for CRAE, 0.23 (95% CI 0.17 to 0.28) for CRVE and 0.18 (95% CI 0.13 to 0.24) for AVR. Mother-child and father-child values were similar (0.20 and 0.32 for CRAE, 0.22 and 0.29 for CRVE, respectively). Relationships attenuated slightly on adjustment for age, sex, blood pressure, diabetes and body mass index. Percentiles and concordance are presented for the whole sample and by sex. CONCLUSIONS: Arteriolar and venular calibre were similar to previously documented measures in midlife adult and late childhood populations. Population parent-child concordance values align with moderate polygenic heritability reported in smaller studies.

18.
Invest Ophthalmol Vis Sci ; 60(8): 3254-3263, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31361305

RESUMO

Purpose: Abnormal blood vessel formation is a defining feature of many blinding eye diseases. Targeting abnormal angiogenesis by inhibiting VEGF has revolutionized the treatment of many ocular angiogenic diseases over the last decade. However, a substantial number of patients are refractory to anti-VEGF treatment or may develop resistance over time. The objective of this study was to determine the efficacy and the mechanism of action of Apratoxin S4 in ocular angiogenesis. Methods: Retinal vascular cell proliferation, migration, and the ability to form tube-like structure were studied in vitro. Ex vivo aortic ring, choroid, and metatarsal assays were used to study Apratoxin S4's impact on vessel outgrowth in a multicellular environment. Apratoxin S4 was also tested in mouse models of oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV), and in a rabbit model of persistent retinal neovascularization (PRNV). Western blot and ELISA were used to determine the expression of key angiogenic regulators after Apratoxin S4 treatment. Results: Apratoxin S4 strongly inhibits retinal vascular cell activation by suppressing multiple angiogenic pathways. VEGF-activated vascular cells and angiogenic vessels are more susceptible to Apratoxin S4 treatment than quiescent vascular cells and vessels. Both intraperitoneal and intravitreal delivery of Apratoxin S4 are able to impede ocular neovascularization in vivo. Apratoxin S4 specifically attenuates pathological ocular angiogenesis and exhibits a combinatorial inhibitory effect with standard-of-care VEGF inhibitor drug (aflibercept). Conclusions: Apratoxin S4 is a potent antiangiogenic drug that inhibits the activation of retinal endothelial cells and pericytes through mediating multiple angiogenic pathways.

19.
Ophthalmol Retina ; 3(11): 985-992, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31331787

RESUMO

PURPOSE: To investigate potential genetic prognostic factors associated with spontaneous resolution of serous retinal detachment (SRD) and development of choroidal neovascularization (CNV) in central serous chorioretinopathy (CSC). DESIGN: Retrospective analysis of a case series. PARTICIPANTS: One hundred ninety-six eyes from 196 patients with active CSC. METHODS: We retrospectively reviewed medical records and determined the presence or absence of SRD using OCT imaging. The duration until the spontaneous SRD resolution was analyzed using the Kaplan-Meier method, and associations between the duration to spontaneous resolution and Complement factor H (CFH) I62V, Age-Related Maculopathy Susceptibility 2 (ARMS2) A69S, or Vasoactive Intestinal Peptide Receptor 2 (VIPR2) rs3793217 genotypes were evaluated, followed by the assessment of their associations with CNV that developed secondary to CSC. MAIN OUTCOME MEASURES: Genetic associations of CFH rs800292, ARMS2 rs10490924, and VIPR2 rs3793217 genotypes with the duration to spontaneous resolution of SRD and development of CNV during follow-up of CSC. RESULTS: In 105 of the 196 study participants, we revealed spontaneous SRD resolution in their eyes during follow-up evaluation. Sixty-eight eyes received treatment, and 23 eyes dropped out before spontaneous SRD resolution. Among the 3 genetic polymorphisms assessed herein, only the CFH I62V genotype was predictive of spontaneous SRD resolution among its genotypes (P = 0.017); the average durations for the spontaneous SRD resolution for the individuals with AA, AG, and GG genotype were 126.6±115.5 days, 157.7±243.1 days, and 242.7±198.0 days, respectively, indicating that the G allele was associated with significantly longer persistent SRD (P = 0.035). Among the total number of eyes of all participants, 14 demonstrated CNV during follow-up evaluation. The CFH I62V G and ARMS2 A69S T alleles were associated significantly with CNV development (P = 0.0023 and P = 0.019, respectively), whereas the VIPR2 rs3793217 genotype was not. CONCLUSIONS: The CFH I62V and ARMS2 A69S genotypes can predict the prognosis of CSC. Knowledge of the genetic status may help physicians determine the need for early treatment and possibly prevent subsequent CNV development. Further prospective studies are needed to confirm the observed genotype-phenotype relationship.

20.
Am J Ophthalmol ; 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31103525

RESUMO

PURPOSE: To determine the association of refractive error (RE) and its associated determinants (axial length [AL], anterior chamber depth (ACD) and corneal curvature [CC]) with the incidence and progression of diabetic retinopathy (DR). DESIGN: Population-based cohort study METHODS: A total of 1562 eyes of 840 individuals with diabetes and gradable retinal photographs (mean age [SD]: 57.0 [8.3] years, 48.2% female), from the Singapore Malay and Indian Eye Studies, at baseline (2004-2009) and follow-up (2011-2015) examinations were included in analyses. RE was calculated as sphere plus half negative cylinder, while AL, ACD and CC were assessed using optical biometry. Incident DR was defined as having no baseline DR and any DR at follow-up; incident vision-threatening DR (VTDR) as no baseline VTDR but present at follow-up; and DR progression as an increase in severity at follow-up from at least minimal baseline DR. Eye-specific data and generalized estimating equation models to account for between-eye correlation were utilized to determine the relationships between the exposures and outcomes, adjusted for traditional DR risk factors. RESULTS: At follow-up, 164 of 1273 (12.9%) had incident DR, 17 of 1542 (1.1%) eyes had incident VTDR, and 75 of 269 (27.9%) eyes with baseline DR experienced progression. A longer AL (per mm increase, risk ratio, 95% confidence interval: 0.58, 0.38, 0.88) was associated with lower risk of incident DR. No other associations were found. CONCLUSION: Our findings show that a longer AL is protective of incident DR.

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