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1.
Ophthalmology ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34763023

RESUMO

PURPOSE: Carriers of functionally deficient mutations in the CYP39A1 gene have been recently reported to have a 2-fold increased risk of exfoliation syndrome (XFS). The aim of this study was to evaluate the risk of blindness and related clinical phenotypes of XFS patients carrying the loss-of-function CYP39A1 G204E mutation in comparison to XFS patients without any CYP39A1 mutation. DESIGN: Retrospective case study PARTICIPANTS: 35 patients diagnosed with XFS carrying the CYP39A1 G204E mutation and 150 XFS patients without any CYP39A1 mutation, who were randomly selected from the Japanese XFS cohort. METHODS: Two-sided Fisher's Exact Test with an α-level <0.05 was used to estimate the significance of the calculated Odds Ratio (OR) for all categorical measures. Comparisons between groups of subjects were performed using linear mixed effect models with group as random effect and taking possible dependence between eyes within a subject into account. MAIN OUTCOME MEASURES: Primary analysis compared the incidence of blindness (defined as visual acuity [VA]<0.05 decimal), prevalence of exfoliation glaucoma (XFG), history of glaucoma surgery, and indices of glaucoma severity such as visual field mean deviation (MD), intraocular pressure (IOP) and vertical cup-disc ratio (CDR), between CYP39A1 G204E carriers and those without any CYP39A1 mutation. RESULTS: The overall risk for blindness was significantly higher in XFS patients carrying the CYP39A1 G204E variant (10/35 [28.6%]) compared to XFS patients without any CYP39A1 mutations (8/150 [5.3%]; OR7.1 [95%CI:2.7-20.2]; p<0.001). A higher proportion of XFS patients with the CYP39A1 G204E mutation (23/35 [65.7%]) had evidence of XFG in at least one eye compared to the comparison group (41/150 [27.3%]; OR5.1 [95%CI:2.4-11.4]; p<0.0001). Significantly higher peak IOP, larger vertical CDR and worse visual field MD were also found in CYP39A1 G204E variant carriers (p<0.001). Additionally, patients with the CYP39A1 G204E mutation (18/35 [51.4%]) required more laser or glaucoma surgical interventions compared to those without any CYP39A1 mutation (32/150 [21.3%], p<0.001). CONCLUSIONS: Patients with XFS carrying the CYP39A1 G204E mutation had significantly increased risk of blindness, higher occurrence of XFG and more severe glaucoma compared to patients with XFS without any CYP39A1 mutation.

2.
Invest Ophthalmol Vis Sci ; 62(14): 17, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34787640

RESUMO

High myopia is among the most common causes of vision impairment, and it is mainly characterized by abnormal elongation of the axial length, leading to pathologic changes in the ocular structures. Owing to the close relationship between high myopia and glaucoma, the association between intraocular pressure (IOP) and high myopia progression has garnered attention. However, whether lowering IOP can retard the progression of high myopia is unclear. On reviewing previous studies, we suggest that lowering IOP plays a role in progressive axial length elongation in high myopia, particularly in pathologic myopia, wherein the sclera is more remodeled. Based on the responses of the ocular layers, we further proposed the potential mechanisms. For the sclera, lowering the IOP could inhibit the activation of scleral fibroblasts and then reduce scleral remodeling, and a decrease in the scleral distending force would retard the ocular expansion like a balloon. For the choroid, lowering IOP results in an increase in choroidal blood perfusion, thereby reducing scleral hypoxia and slowing down scleral remodeling. The final effect of these pathways is slowing axial elongation and the development of scleral staphyloma. Further animal and clinical studies regarding high myopia with varied degree of IOP and the changes of choroid and sclera during IOP fluctuation in high myopia are needed to verify the role of IOP in the pathogenesis and progression of high myopia. It is hoped that this may lead to the development of a prospective treatment option to prevent and control high myopia progression.

3.
Clin Ophthalmol ; 15: 4455-4465, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34819717

RESUMO

Purpose: To investigate features of the steady-state pattern electroretinogram (ssPERG) in subjects with glaucoma (G), high myopia (HM; spherical equivalent ≤-6D) and glaucoma with high myopia (GHM). Patients and Methods: Our study included 48 participants divided into 3 groups (G, HM, and GHM) who each underwent monocular ssPERG testing with Diopsys NOVA PERG protocols. The ConStim protocol detects distinct topographic patterns of dysfunction 16° and 24° around the central macula. MagD is the amplitude of the average signal and MagD/Mag ratio indicates the consistency of the response. ssPERG indices were compared between groups and correlated with functional (ie, visual field mean deviation (VFMD)) and structural (ie, average retinal nerve fibre layer (RNFL) thickness; Cirrus optical coherence tomography) features. Results: Participants had an average age of 59.4±7.6 years. Mean Humphrey VFMD was -14.22 ± 2.88dB, -2.62 ± 1.18dB and -12.80 ± 2.60dB for G, HM and GHM groups, respectively. Mean RNFL thickness was 63.0 ± 8.20µm, 69.5 ± 15.7µm and 60.6 ± 5.0µm for G, HM and GHM groups, respectively. For the 24° setting, no significant differences were noted for any of the parameters. For the 16° setting, MagD was lower in the GHM group compared to the HM group (0.29µV vs 0.52µV; p = 0.02). Significant differences were noted for the MagD/Mag ratio between HM and G groups (0.58 vs 0.40; p = 0.02) and between HM and GHM groups (0.58 vs 0.35; p = 0.002). There were positive correlations between both MagD 16° and MagD/Mag ratio 16° with VFMD (correlation coefficient [r]=0.37, p = 0.009; and r = 0.44, p = 0.002, respectively) and RNFL (r = 0.43, p = 0.002; and r = 0.48, p = 0.001, respectively). Conclusion: MagD/Mag ratio at 16° was significantly lower in glaucomatous eyes (with or without high myopia) compared to those with high myopia without glaucoma, suggesting that glaucoma has a distinct impact on MagD/Mag ratio at 16° irrespective of the presence of myopia.

5.
Br J Ophthalmol ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34670749

RESUMO

PURPOSE: To assess the generalisability and performance of a deep learning classifier for automated detection of gonioscopic angle closure in anterior segment optical coherence tomography (AS-OCT) images. METHODS: A convolutional neural network (CNN) model developed using data from the Chinese American Eye Study (CHES) was used to detect gonioscopic angle closure in AS-OCT images with reference gonioscopy grades provided by trained ophthalmologists. Independent test data were derived from the population-based CHES, a community-based clinic in Singapore, and a hospital-based clinic at the University of Southern California (USC). Classifier performance was evaluated with receiver operating characteristic curve and area under the receiver operating characteristic curve (AUC) metrics. Interexaminer agreement between the classifier and two human examiners at USC was calculated using Cohen's kappa coefficients. RESULTS: The classifier was tested using 640 images (311 open and 329 closed) from 127 Chinese Americans, 10 165 images (9595 open and 570 closed) from 1318 predominantly Chinese Singaporeans and 300 images (234 open and 66 closed) from 40 multiethnic USC patients. The classifier achieved similar performance in the CHES (AUC=0.917), Singapore (AUC=0.894) and USC (AUC=0.922) cohorts. Standardising the distribution of gonioscopy grades across cohorts produced similar AUC metrics (range 0.890-0.932). The agreement between the CNN classifier and two human examiners (Ò =0.700 and 0.704) approximated interexaminer agreement (Ò =0.693) in the USC cohort. CONCLUSION: An OCT-based deep learning classifier demonstrated consistent performance detecting gonioscopic angle closure across three independent patient populations. This automated method could aid ophthalmologists in the assessment of angle status in diverse patient populations.

6.
Ophthalmology ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34619247

RESUMO

PURPOSE: To develop and evaluate the performance of a 3-dimensional (3D) deep-learning-based automated digital gonioscopy system (DGS) in detecting 2 major characteristics in eyes with suspected primary angle-closure glaucoma (PACG): (1) narrow iridocorneal angles (static gonioscopy, Task I) and (2) peripheral anterior synechiae (PAS) (dynamic gonioscopy, Task II) on OCT scans. DESIGN: International, cross-sectional, multicenter study. PARTICIPANTS: A total of 1.112 million images of 8694 volume scans (2294 patients) from 3 centers were included in this study (Task I, training/internal validation/external testing: 4515, 1101, and 2222 volume scans, respectively; Task II, training/internal validation/external testing: 378, 376, and 102 volume scans, respectively). METHODS: For Task I, a narrow angle was defined as an eye in which the posterior pigmented trabecular meshwork was not visible in more than 180° without indentation in the primary position captured in the dark room from the scans. For Task II, PAS was defined as the adhesion of the iris to the trabecular meshwork. The diagnostic performance of the 3D DGS was evaluated in both tasks with gonioscopic records as reference. MAIN OUTCOME MEASURES: The area under the curve (AUC), sensitivity, and specificity of the 3D DGS were calculated. RESULTS: In Task I, 29.4% of patients had a narrow angle. The AUC, sensitivity, and specificity of 3D DGS on the external testing datasets were 0.943 (0.933-0.953), 0.867 (0.838-0.895), and 0.878 (0.859-0.896), respectively. For Task II, 13.8% of patients had PAS. The AUC, sensitivity, and specificity of 3D DGS were 0.902 (0.818-0.985), 0.900 (0.714-1.000), and 0.890 (0.841-0.938), respectively, on the external testing set at quadrant level following normal clinical practice; and 0.885 (0.836-0.933), 0.912 (0.816-1.000), and 0.700 (0.660-0.741), respectively, on the external testing set at clock-hour level. CONCLUSIONS: The 3D DGS is effective in detecting eyes with suspected PACG. It has the potential to be used widely in the primary eye care community for screening of subjects at high risk of developing PACG.

7.
Ophthalmology ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34634364

RESUMO

PURPOSE: To assess baseline ocular biometric risk factors for progression from primary angle closure suspect (PACS) to primary angle closure (PAC) or acute angle closure (AAC). DESIGN: Prospective, observational study. PARTICIPANTS: Six hundred forty-three mainland Chinese with untreated PACS. METHODS: Participants underwent baseline clinical examinations, including gonioscopy, anterior segment OCT (AS-OCT) imaging, and A-scan ultrasound biometry as part of the Zhongshan Angle Closure Prevention (ZAP) Trial. Primary angle closure suspect was defined as an inability to visualize pigmented trabecular meshwork in 2 or more quadrants based on static gonioscopy. Primary angle closure was defined as development of intraocular pressure above 24 mmHg or peripheral anterior synechiae. Progression was defined as development of PAC or an AAC attack. Multivariable logistic regression models were developed to assess biometric risk factors for progression. MAIN OUTCOME MEASURES: Six-year progression from PACS to PAC or AAC. RESULTS: Six hundred forty-three untreated eyes (609 nonprogressors, 34 progressors) of 643 participants were analyzed. In a multivariable model with continuous parameters, narrower horizontal angle opening distance of 500 µm from the scleral spur (AOD500; odds ratio [OR], 1.10 per 0.01-mm decrease; P = 0.03), flatter horizontal iris curvature (IC; OR, 1.96 per 0.1-mm decrease; P = 0.01), and older age (OR, 1.11 per 1-year increase; P = 0.01) at baseline were associated significantly with progression (area under the receiver operating characteristic curve [AUC], 0.73). Smaller cumulative gonioscopy score was not associated with progression (OR, 1.03 per 1-modified Shaffer grade decrease; P = 0.85) when replacing horizontal AOD500 in the multivariable model. In a separate multivariable model with categorical parameters, participants in the lowest quartile of horizontal AOD500 (OR, 3.10; P = 0.002) and IC (OR, 2.48; P = 0.014) measurements and 59 years of age or older (OR, 2.68; P = 0.01) at baseline showed higher odds of progression (AUC, 0.72). CONCLUSIONS: Ocular biometric measurements can help to risk-stratify patients with early angle closure for more severe disease. Anterior segment OCT measurements of biometric parameters describing the angle and iris are predictive of progression from PACS to PAC or AAC, whereas gonioscopy grades are not.

8.
Ophthalmol Glaucoma ; 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34718222

RESUMO

PURPOSE: Detection of early glaucoma remains limited with the conventional analysis of the retinal nerve fiber layer (RNFL). To assess whether compensating the RNFL thickness for multiple demographic and anatomical factors improves the detection of glaucoma. DESIGN: Cross-sectional study METHODS: 2699 healthy participants were enrolled to construct and test a multivariable compensation model, which was then applied in 387 healthy and 387 glaucoma participants (early, n=219; moderate, n=97; and, advanced, n=71). Participants underwent Cirrus spectral-domain optical coherence tomography (OCT; Carl Zeiss Meditec) imaging of the optic disc and macular cubes. Compensated RNFL thickness was generated based on ethnicity, age, refractive error, optic disc (ratio, orientation, and area), fovea (distance and angle), and retinal vessel density. RNFL thickness measurements and their corresponding areas under the receiver operating characteristic curves (AUCs) were obtained. MAIN OUTCOME AND MEASURES: Measured and compensated RNFL thickness measurements RESULTS: After applying the Asian-specific compensation model, the standard deviation (SD) of RNFL thickness reduced, where the effect was greatest for Chinese (16.9%), followed by Malays (13.9%) and then Indians (12.1%). Multivariable normative comparison outperformed measured RNFL for discrimination of early glaucoma (AUC=0.90 vs 0.85; P<0.001), moderate glaucoma (AUC=0.94 vs 0.91; P<0.001) and advanced glaucoma (AUC=0.98 vs 0.96; P<0.001). CONCLUSIONS: The multivariable normative database of RNFL showed better glaucoma discrimination capability than conventional age-matched comparisons, suggesting there may be utility in accounting for demographic and anatomical variance in RNFL thickness to improve glaucoma detection.

9.
Invest Ophthalmol Vis Sci ; 62(13): 29, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34714323

RESUMO

Purpose: To evaluate the biomechanical properties of the iris by evaluating iris movement during pupil constriction and to compare such properties between healthy and primary angle-closure glaucoma (PACG) subjects. Methods: A total of 140 subjects were recruited for this study. In a dark room, the anterior segments of one eye per subject were scanned using anterior segment optical coherence tomography imaging during induced pupil constriction with an external white light source of 1700 lux. Using a custom segmentation code, we automatically isolated the iris segments from the AS-OCT images, which were then discretized and transformed into a three-dimensional point cloud. For each iris, a finite element (FE) mesh was constructed from the point cloud, and an inverse FE simulation was performed to match the clinically observed iris constriction in the AS-OCT images. Through this optimization process, we were able to identify the elastic modulus and permeability of each iris. Results: For all 140 subjects (95 healthy and 45 PACG of Indian/Chinese ethnicity; age 60.2 ± 8.7 for PACG subjects and 57.7 ± 10.1 for healthy subjects), the simulated deformation pattern of the iris during pupil constriction matched well with OCT images. We found that the iris stiffness was higher in PACG than in healthy controls (24.5 ± 8.4 kPa vs. 17.1 ± 6.6 kPa with 40 kPa of active stress specified in the sphincter region; P < 0.001), whereas iris permeability was lower (0.41 ± 0.2 mm2/kPa s vs. 0.55 ± 0.2 mm2/kPa s; p = 0.142). Conclusions: This study suggests that the biomechanical properties of the iris in PACG are different from those in healthy controls. An improved understanding of the biomechanical behavior of the iris may have implications for the understanding and management of angle-closure glaucoma.


Assuntos
Glaucoma de Ângulo Fechado/fisiopatologia , Pressão Intraocular/fisiologia , Iris/fisiopatologia , Elasticidade , Feminino , Glaucoma de Ângulo Fechado/diagnóstico , Glaucoma de Ângulo Fechado/metabolismo , Gonioscopia , Humanos , Iris/patologia , Masculino , Pessoa de Meia-Idade , Permeabilidade , Tomografia de Coerência Óptica/métodos
10.
Ophthalmology ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34592243

RESUMO

PURPOSE: We hypothesized that the effect of blood lipid-related metabolites on primary open-angle glaucoma (POAG) would differ according to specific lipoprotein particles and lipid sub-fractions. We investigated the associations of blood levels of lipoprotein particles and lipid sub-fractions with POAG. DESIGN: Cross-sectional study. PARTICIPANTS: Individuals recruited for the baseline visit of the population-based Singapore Epidemiology of Eye Disease study (n = 8503). METHODS: All participants underwent detailed standardized ocular and systemic examinations. A total of 130 blood lipid-related metabolites were quantified using a nuclear magnetic resonance metabolomics platform. The analyses were conducted in 2 stages. First, we investigated whether and which lipid-related metabolites were directly associated with POAG using regression analyses followed by Bayesian network modeling. Second, we investigated if any causal relationship exists between the identified lipid-related metabolites, if any, and POAG using 2-sample Mendelian randomization (MR) analysis. We performed genome-wide association studies (GWAS) on high-density lipoprotein (HDL) 3 cholesterol (after inverse normal transformation) and used the top variants associated with HLD3 cholesterol as instrumental variables (IVs) in the MR analysis. MAIN OUTCOME MEASURE: Primary open-angle glaucoma. RESULTS: Of the participants, 175 (2.1%) had POAG. First, a logistic regression model showed that total HDL3 cholesterol (negatively) and phospholipids in very large HDL (positively) were associated with POAG. Further analyses using a Bayesian network analysis showed that only total HDL3 cholesterol was directly associated with POAG (odds ratio [OR], 0.72 per 1 standard deviation increase in HDL3 cholesterol; 95% confidence interval [CI], 0.61-0.84), independently of age, gender, intraocular pressure (IOP), body mass index (BMI), education level, systolic blood pressure, axial length, and statin medication. Using 5 IVs identified from the GWAS and with the inverse variance weighted MR method, we found that higher levels of HDL3 cholesterol were associated with a decreased odds of POAG (OR, 0.91; 95% CI, 0.84-0.99, P = 0.021). Other MR methods, including weighted median, mode-based estimator, and contamination mixture methods, derived consistent OR estimates. None of the routine lipids (blood total, HDL, or low-density lipoprotein [LDL] cholesterol) were associated with POAG. CONCLUSIONS: Overall, these results suggest that the relationship between HDL3 cholesterol and POAG might be causal and specific, and that dysregulation of cholesterol transport may play a role in the pathogenesis of POAG.

11.
Ophthalmic Genet ; : 1-6, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34425738

RESUMO

BACKGROUND: Glaucomatous optic nerve damage is caused by selective death of retinal ganglion cells (RGCs). Another condition with underlying loss of RGCs is autosomal dominant optic atrophy (ADOA). Majority of ADOA patients have mutations in OPA1, gene responsible for mitochondrial fusion final steps. Clinical resemblance between the two diseases make genes involved in mitochondrial fusion good candidates as glaucoma genes. In this study, we investigated if selected polymorphisms of OPA1, MFN1, and MFN2 were associated with glaucoma in Polish population. METHODS: Four OPA1 (rs166850, rs10451941, rs7624750, rs9851685), one MFN1 (rs2111534), and two MFN2 (rs873458, rs2295281) single nucleotide polymorphisms were investigated in 304 primary open angle glaucoma patients (204 with normal tension glaucoma, 100 with high-tension glaucoma) and 258 control subjects using RT-PCR method. RESULTS: There was a significant difference in genotype frequencies of rs9851685 and rs2111534 polymorphisms between glaucoma patients and control subjects. Several genotype combinations comprising SNPs at OPA1 and MFN1 were significantly differently distributed in a three-way comparison between controls, patients with NTG and patients with HTG. None of the studied MFN2 polymorphisms was significantly associated with HTG or NTG. CONCLUSIONS: In studied population, genotype CC and allele C of rs9851685 OPA1 polymorphism are NTG risk factors, whereas TT genotype and T allele of this polymorphism are protective factors against NTG. Genotype GA of rs2111534 MFN1 polymorphism is an HTG risk factor and AA genotype of this polymorphism is a protective factor against HTG. Several OPA1 and MFN2 genotype combinations are significantly associated with either increased or decreased risk of glaucoma in this population.

12.
Br J Ophthalmol ; 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433548

RESUMO

INTRODUCTION: Laser trabeculoplasty is an effective and widely used treatment for glaucoma. A new laser technology, the Eagle direct selective laser trabeculoplasty (DSLT) device, may provide automated, fast, simple, safe and effective laser treatment for glaucoma in a broader range of clinical settings. This trial aims to test the hypothesis that translimbal DSLT is effective and not inferior to selective laser trabeculoplasty (SLT) in reducing intraocular pressure (IOP) in open angle glaucoma (OAG). METHODS AND ANALYSIS: This is a multicentre, randomised, controlled, investigator-masked study. The primary efficacy outcome is intergroup difference in mean change from baseline IOP measured at 6 months. Secondary outcomes include mean percentage reduction in IOP at 3, 6 and 12 months; proportion of participants with at least 20% reduction in IOP from baseline at 6 months; change in ocular hypotensive medications at 12 months and evaluation of safety. Participants were aged >= 40 years with OAG, including exfoliative or pigmentary glaucoma, or ocular hypertension with untreated or washed out IOP 22-35 mm Hg. TREATMENTS: DSLT: 120 shots, 3 ns, 400 µm spot size, energy 1.4-1.8 mJ delivered at the limbus over 2 s. SLT: approximately 100 shots, 3 ns, 400 µm spot size administered 360 degrees at the limbus using any gonioscopy lens, energy 0.3-2.6 mJ. A sample size of 164 is sufficient to detect a non-inferiority margin of 1.95 mm Hg for change from baseline IOP. CLINICAL TRIAL REGISTRATION NUMBER: NCT03750201, ISRCTN14033075.

13.
Ophthalmology ; 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34339778

RESUMO

PURPOSE: To develop and validate a multimodal artificial intelligence algorithm, FusionNet, using the pattern deviation probability plots from visual field (VF) reports and circular peripapillary OCT scans to detect glaucomatous optic neuropathy (GON). DESIGN: Cross-sectional study. SUBJECTS: Two thousand four hundred sixty-three pairs of VF and OCT images from 1083 patients. METHODS: FusionNet based on bimodal input of VF and OCT paired data was developed to detect GON. Visual field data were collected using the Humphrey Field Analyzer (HFA). OCT images were collected from 3 types of devices (DRI-OCT, Cirrus OCT, and Spectralis). Two thousand four hundred sixty-three pairs of VF and OCT images were divided into 4 datasets: 1567 for training (HFA and DRI-OCT), 441 for primary validation (HFA and DRI-OCT), 255 for the internal test (HFA and Cirrus OCT), and 200 for the external test set (HFA and Spectralis). GON was defined as retinal nerve fiber layer thinning with corresponding VF defects. MAIN OUTCOME MEASURES: Diagnostic performance of FusionNet compared with that of VFNet (with VF data as input) and OCTNet (with OCT data as input). RESULTS: FusionNet achieved an area under the receiver operating characteristic curve (AUC) of 0.950 (0.931-0.968) and outperformed VFNet (AUC, 0.868 [95% confidence interval (CI), 0.834-0.902]), OCTNet (AUC, 0.809 [95% CI, 0.768-0.850]), and 2 glaucomatologists (glaucomatologist 1: AUC, 0.882 [95% CI, 0.847-0.917]; glaucomatologist 2: AUC, 0.883 [95% CI, 0.849-0.918]) in the primary validation set. In the internal and external test sets, the performances of FusionNet were also superior to VFNet and OCTNet (FusionNet vs VFNet vs OCTNet: internal test set 0.917 vs 0.854 vs 0.811; external test set 0.873 vs 0.772 vs 0.785). No significant difference was found between the 2 glaucomatologists and FusionNet in the internal and external test sets, except for glaucomatologist 2 (AUC, 0.858 [95% CI, 0.805-0.912]) in the internal test set. CONCLUSIONS: FusionNet, developed using paired VF and OCT data, demonstrated superior performance to both VFNet and OCTNet in detecting GON, suggesting that multimodal machine learning models are valuable in detecting GON.

14.
Ophthalmology ; 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34453952

RESUMO

PURPOSE: To examine the efficacy of laser peripheral iridotomy (LPI) in patients who received a diagnosis of primary angle-closure suspect (PACS). DESIGN: Prospective, randomized controlled trial. PARTICIPANTS: This multicenter, randomized controlled trial (ClinicalTrials.gov identifier, NCT00347178) enrolled 480 patients older than 50 years from glaucoma clinics in Singapore with bilateral asymptomatic PACS (defined as having ≥2 quadrants of appositional angle closure on gonioscopy). METHODS: Each participant underwent prophylactic LPI in 1 randomly selected eye, whereas the fellow eye served as a control. Patients were followed up yearly for 5 years. MAIN OUTCOME MEASURES: The primary outcome measure was development of primary angle closure (PAC; defined as presence of peripheral anterior synechiae, intraocular pressure [IOP] of >21 mmHg, or both or acute angle closure [AAC]) or primary angle-closure glaucoma (PACG) over 5 years. RESULTS: Of the 480 randomized participants, most were Chinese (92.7%) and were women (75.8%) with mean age of 62.8 ± 6.9 years. Eyes treated with LPI reached the end point less frequently after 5 years (n = 24 [5.0%]; incidence rate [IR], 11.65 per 1000 eye-years) compared with control eyes (n = 45 [9.4%]; IR, 21.84 per 1000 eye-years; P = 0.001). The adjusted hazard ratio (HR) for progression to PAC was 0.55 (95% confidence interval [CI], 0.37-0.83; P = 0.004) in LPI-treated eyes compared with control eyes. Older participants (per year; HR, 1.06; 95% CI, 1.03-1.10; P < 0.001) and eyes with higher baseline IOP (per millimeter of mercury; HR, 1.35; 95% CI, 1.22-1.50; P < 0.0001) were more likely to reach an end point. The number needed to treat to prevent an end point was 22 (95% CI, 12.8-57.5). CONCLUSIONS: In patients with bilateral asymptomatic PACS, eyes that underwent prophylactic LPI reached significantly fewer end points compared with control eyes over 5 years. However, the overall incidence of PAC or PACG was low.

15.
Br J Ophthalmol ; 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193408

RESUMO

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.

16.
Curr Eye Res ; : 1-8, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253093

RESUMO

Purpose: To evaluate the inter- and intra-observer reliability of anterior chamber (AC) angle measurements obtained by swept-source optical coherence tomography (SS-OCT).Methods: 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.Results: 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.Conclusions: 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.

17.
Sci Rep ; 11(1): 13906, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230538

RESUMO

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 (ß = 0.20, p < 0.001), worse visual field mean deviation (ß = - 0.20, p = 0.01) and narrower AOD750 (ß = - 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.


Assuntos
Segmento Anterior do Olho/patologia , Glaucoma de Ângulo Fechado/patologia , Doenças da Íris/patologia , Idoso , Segmento Anterior do Olho/fisiopatologia , Feminino , Glaucoma de Ângulo Fechado/fisiopatologia , Humanos , Pressão Intraocular , Doenças da Íris/fisiopatologia , Masculino , Fatores de Risco , Índice de Gravidade de Doença
18.
Am J Ophthalmol ; 233: 68-77, 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34283974

RESUMO

PURPOSE: To evaluate the diagnostic performance of swept-source anterior segment optical coherence tomography (SS-OCT) in differentiating eyes with primary angle closure disease (PACD) from eyes of control subjects, as well as eyes with PAC and PAC glaucoma (PACG) from eyes with PAC suspect (PACS) disease. DESIGN: Multicenter cross-sectional study. METHODS: Chinese patients were classified into control, PACS, and PAC/PACG groups. The area under the receiving operating characteristic 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 2928 SS-OCT images from 366 eyes of 260 patients were recruited to develop diagnostic models. The validation dataset included 1176 SS-OCT images from 147 eyes of 143 patients. For distinguishing PACD from control eyes, average anterior chamber depth had the highest AUC (0.94). With a cutoff of 2.2 mm for average anterior chamber depth, the sensitivity and specificity were 90.2% and 85.2% in the training set. For distinguishing PAC/PACG from PACS, a multivariate model had an AUC of 0.83, with sensitivity and specificity of 82.0% and 62.8% in the training set. The validation set confirmed the findings. CONCLUSIONS: SS-OCT of the anterior segment showed excellent diagnostic performance distinguishing PACD from normal eyes and moderate diagnostic ability distinguishing eyes with PAC/PACG from eyes with PACS. ACD alone may provide a simple and effective way to diagnose PACD from control subjects. As ACD can be obtained using other more available modalities, this has implications for the early diagnosis of PACD.

19.
Am J Ophthalmol ; 2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34157276

RESUMO

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.

20.
JAMA Ophthalmol ; 139(8): 866-874, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34165504

RESUMO

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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