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1.
Adv Nutr ; 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32627818

RESUMO

Cerebral vascular diseases are the most common high-mortality diseases worldwide. Their onset and development are associated with glycemic imbalance, genetic background, alteration of atherosclerotic factors, severe inflammation, and abnormal cholesterol metabolism. Recently, the gut-brain axis has been highlighted as the key to the solution for cerebral vessel dysfunction in view of cholesterol metabolism and systemic lipid circulation. In particular, glucagon-like peptide 1 (GLP-1) is a cardinal hormone that regulates blood vessel function and cholesterol homeostasis and acts as a critical messenger between the brain and gut. GLP-1 plays a systemic regulatory role in cholesterol homeostasis and blood vessel function in various organs through blood vessels. Even though GLP-1 has potential in the treatment and prevention of cerebral vascular diseases, the importance of and relation between GLP-1 and cerebral vascular diseases are not fully understood. Herein, we review recent findings on the functions of GLP-1 in cerebral blood vessels in association with cholesterol metabolism.

2.
Br J Ophthalmol ; 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32580957

RESUMO

BACKGROUND/AIMS: To investigate whether the association of long-term intraocular pressure (IOP) fluctuation with the rate of progression of normal-tension glaucoma (NTG) differs between myopia and non-myopia. METHODS: The medical records of 65 myopic NTG (axial length (AL) > 24.0 mm) and 64 non-myopic NTG eyes (AL < 24.0 mm), who had been treated with topical medications for more than 5 years, were reviewed. Multiple linear regression models were fitted to analyse the relationships of the slope of mean deviation (MD) or visual field index (VFI) with the clinical factors, including the interactions with myopia. RESULTS: The average follow-up period was 8.3 years. Twenty-two (22) non-myopic eyes (34.4%) and 27 myopic eyes (41.5%) showed NTG progression (p=0.511). The interaction of myopia with IOP fluctuation was a significant factor regarding both MD and VFI slope (p=0.002, 0.024, respectively); stratified analyses suggested that the risk effect of IOP fluctuation was significant only in myopic NTG in terms of both MD (ß= -1.27, p=0.003) and VFI slope (ß=-2.32, p=0.011). CONCLUSION: Long-term IOP fluctuation was significantly related to faster visual field progression in myopic NTG eyes, compared with non-myopic NTG eyes.

3.
Eye (Lond) ; 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32499586

RESUMO

PURPOSE: To investigate the association between the laminar dot sign (LDS) and the deep optic nerve head (ONH) structure in eyes with primary-open-angle glaucoma (POAG). METHODS: Eighty-four eyes of 84 patients with POAG were prospectively included. All of the patients underwent stereo optic disc photography (SDP), red-free retinal nerve fibre layer (RNFL) photography, SS-OCT, and standard automated perimetry. By evaluating the SDP, patients were classified into laminar dot sign (LDS) and non-LDS groups. The deep structure of the ONH including the anterior prelaminar depth (APLD) and prelaminar tissue thickness (PTT) were quantitated using SS-OCT. Progression was assessed by structural or functional deterioration during the average 4.3 ± 1.2 years of follow-up. RESULTS: The LDS group had deeper APLD (405.47 ± 107.55 vs. 302.45 ± 149.51, P < 0.001) and thinner PTT (74.34 ± 24.46 vs. 137.29 ± 40.07, P = 0.001) relative to the non-LDS group. By multivariate analysis, thin PTT was significantly associated with the presence of LDS (odds ratio = 0.939, P < 0.001). Structural progression was detected in 45 eyes (84.9%) in the LDS group and 8 eyes (25.8%) in the non-LDS group. Functional progression was demonstrated in 29 eyes (34.5%) in the LDS group and 6 eyes (19.4%) in the non-LDS group. The eyes with LDS had a significantly higher risk of glaucoma progression (χ2 = 5.00, degree of freedom = 1, P = 0.033). CONCLUSIONS: In eyes with POAG, the presence of LDS was associated with thinner prelaminar tissue and faster disease progression.

4.
Ophthalmology ; 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32417391

RESUMO

PURPOSE: To investigate 24-hour nyctohemeral intraocular pressure (IOP)-related patterns with contact lens sensors (CLS) in eyes with primary open-angle glaucoma (POAG) with normal baseline IOP (i.e., normal-tension glaucoma, NTG) and healthy controls. DESIGN: Prospective, case-control study. PARTICIPANTS: Thirty (30) eyes of 30 NTG patients, who had had a wash-out period for their IOP-lowering treatment, and 20 eyes of 20 healthy volunteer subjects. METHODS: Patients and subjects were hospitalized for the purposes of 24-hour CLS (SENSIMED Triggerfish; Sensimed AG, Lausanne, Switzerland) measurement. The IOP-related patterns during wake and sleep times over the course of the 24 hours were compared between the two groups. The 24-hour ambulatory blood pressure and posture were monitored simultaneously. A generalized linear model was used to find the factors associated with NTG. MAIN OUTCOME MEASURES: IOP-related patterns, including mean and standard deviation (SD) of measurements, amplitude of cosine-fit curve, acrophase (signal peak) and bathyphase (signal trough) values (mVEq). RESULTS: The SD of the 24-hour CLS measurements were significantly greater in NTG eyes than in healthy controls (112.51 ± 26.90 vs. 85.18 ± 29.61 mVEq, P = 0.002). The amplitudes of cosine-fit curve (141.88 ± 39.96 vs. 106.08 ± 41.49 mVEq, P = 0.004) and acrophase values (277.74 ± 129.80 vs. 190.58 ± 127.88 mVEq, P = 0.024), mostly measured during nocturnal period, were significantly greater in NTG eyes than in healthy controls. NTG subjects slept longer in the lateral decubitus posture than did the healthy controls (199.1 ± 137.8 vs. 113.2 ± 86.2 minutes, P = 0.009). In the multivariable generalized linear model, the greater amplitude of cosine-fit curve (ß = 0.218, P = 0.012) and greater time of decubitus posture during sleep (ß = 0.180, P = 0.004) were found to be significantly associated with NTG. CONCLUSIONS: Continuous monitoring of 24-hour IOP-related values with CLS can be useful for assessment of glaucoma risk, especially for NTG patients whose IOP appears to be in the normal range. Fluctuation of 24-hour IOP-related values and posture during sleep time might be associated with NTG.

5.
Int J Mol Sci ; 21(9)2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32375326

RESUMO

Vascular calcification (VC) is characterized by calcium deposition inside arteries and is closely associated with the morbidity and mortality of atherosclerosis, chronic kidney disease, diabetes, and other cardiovascular diseases (CVDs). VC is now widely known to be an active process occurring in vascular smooth muscle cells (VSMCs) involving multiple mechanisms and factors. These mechanisms share features with the process of bone formation, since the phenotype switching from the contractile to the osteochondrogenic phenotype also occurs in VSMCs during VC. In addition, VC can be regulated by epigenetic factors, including DNA methylation, histone modification, and noncoding RNAs. Although VC is commonly observed in patients with chronic kidney disease and CVD, specific drugs for VC have not been developed. Thus, discovering novel therapeutic targets may be necessary. In this review, we summarize the current experimental evidence regarding the role of epigenetic regulators including histone deacetylases and propose the therapeutic implication of these regulators in the treatment of VC.

6.
Invest Ophthalmol Vis Sci ; 61(4): 20, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32301971

RESUMO

Purpose: To compare the macular interdigitation zone (IZ) of normal eyes with eyes showing different normal-tension glaucoma (NTG) stages. Methods: Forty-two normal eyes (age, 56 ± 5.4 years), 45 pre-perimetric eyes (age, 59 ± 6.9 years), 51 mild-to-moderate glaucoma eyes (age, 58 ± 7.2 years; mean deviation [MD], -5.5 ± 3.0 dB), and 50 severe glaucoma eyes (age, 59 ± 6.9 years; MD, -15.1 ± 5.4 dB) were enrolled. All of the subjects underwent high-resolution spectral-domain optical coherence tomography (SD-OCT) to obtain 19 horizontal and 19 vertical macular B-scans 9 mm in length. The en face image of the scan area was divided into 589 rectangular boxes (side length of 375 µm). The IZ locations were marked on the corresponding image boxes. The IZ area was then quantified according to the number of boxes showing IZs among the 589 total boxes. Results: The IZ area in the severe glaucoma eyes was significantly smaller than in the mild-to-moderate glaucoma eyes (28.99 ± 7.88 mm2 vs. 40.79 ± 7.46 mm2; P < 0.001), was smaller in the mild-to-moderate glaucoma eyes than in the pre-perimetric glaucoma eyes (40.79 ± 7.46 mm2 vs. 49.92 ± 8.10 mm2; P < 0.001), and was smaller still in the pre-perimetric glaucoma eyes than in the normal eyes (49.92 ± 8.10 mm2 vs. 56.85 ± 7.94 mm2; P < 0.001). In the 146 NTG eyes, a statistically significant correlation was found between IZ area and MD (r = 0.64; P < 0.001). Conclusions: SD-OCT revealed a reduction in IZ area in NTG eyes, and the extent of the reduction was positively associated with glaucoma severity. These findings suggest, though tentatively, that changes in the outer retinal layer can occur in the course of glaucoma progression.

7.
Br J Ophthalmol ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32345605

RESUMO

BACKGROUND/AIMS: To investigate the associations between the morphological characteristics of beta-zone parapapillary atrophy (ß-zone PPA) and subsequent visual field (VF) progression in eyes with primary open-angle glaucoma (POAG). METHODS: One hundred and twenty-one POAG eyes with ß-zone PPA along with 48 normal eyes with ß-zone PPA were included. ß-zone PPA area was calculated based on the PPA pixel area/optic-disc pixel area ratio and the optical coherence tomography (OCT)-measured disc area. ß-zone PPA margin irregularity was quantified as a function of both area (A) and perimeter (P, calculated as 1/(4πA/P²)). VF progression was defined using standard automated perimetry's guided progression analysis software. RESULTS: Of the 121 POAG eyes, 49 (40.5%) showed VF progression during the 10.1±1.9 years of follow-up. The baseline ß-zone PPA area was similar among the three groups (Progressors, Non-progressors and Controls, p=0.995). However, the ß-zone PPA irregularity index was significantly higher in the Progressors (p<0.001). The cumulative probability of VF progression was greater in the higher PPA irregularity index group (p<0.001, log-rank test). A Cox proportional hazards model showed the significant influences of optic disc haemorrhage (HR: 2.661, p=0.034) and higher baseline PPA irregularity index (HR: 1.455, p=0.007) on subsequent progression. CONCLUSIONS: In POAG eyes, baseline ß-zone PPA margin regularity was significantly associated with subsequent VF progression. Irregular margin of ß-zone PPA might be the mark of vulnerability in the parapapillary area to further glaucomatous damage.

8.
Am J Ophthalmol ; 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32222365

RESUMO

PURPOSE: To investigate the over-5-year natural clinical course and risk factors of progression in preperimetric open angle glaucoma (OAG) of 'young age of onset (under age 40)' without treatment. DESIGN: Retrospective observational case series. METHODS: Disc photography, red-free retinal nerve fiber layer (RNFL) photography, optical coherence tomography, and visual field (VF) examinations were performed every 6 months. Glaucoma progression was defined as structural or functional deterioration. Linear mixed-effects model was used to estimate the rate of structural and functional change. Kaplan-Meier survival analysis and log-rank testing were used to compare survival experiences, and Cox proportional hazards modeling was performed to identify risk factors for glaucoma progression. RESULTS: Of the 98 eyes of 98 patients (mean age: 30.6 years), glaucoma progression was detected in 42 eyes (42.9%). The rate of average RNFL thickness thinning was -0.46±0.50 µm/yr, and the mean deviation (MD) change was -0.03±0.13 dB/yr. The glaucoma progression probability at 5 years was 39% by structural criteria and 5% by functional criteria. Older age at diagnosis (P=.004), presence of temporal raphe sign (horizontal straight line on macular ganglion cell-inner plexiform layer thickness map) (P=.011), lamina pore visibility (P=.034), and greater pattern standard deviation (PSD) (P= .005) were significant factors for glaucoma progression. CONCLUSIONS: In untreated preperimetric OAG patients of 'young age of onset', the estimated mean MD slope for over-5-years was -0.03 dB/yr and the average RNFL thickness thinning rate was -0.46 µm/yr. The predictors for progression were structural parameters of temporal raphe sign, lamina pore visibility, and functional parameter of PSD.

9.
Ophthalmology ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32222399

RESUMO

PURPOSE: To investigate the difference in longitudinal change of ß-zone parapapillary atrophy (PPA) between eyes with primary open-angle glaucoma (POAG) and normal eyes. DESIGN: Longitudinal, observation study. PARTICIPANTS: A total of 153 eyes with POAG and 105 normal eyes. METHODS: Participants were followed for 10 years or more, with disc photography performed every year. The topographic parameters of ß-zone PPA (area, maximal radial extent, angular extent around disc) were measured. The factors associated with the enlargement of ß-zone PPA parameters were assessed by odds ratio (OR) using multivariable logistic regression. MAIN OUTCOME MEASURES: Enlargement of ß-zone PPA parameters and associated factors. RESULTS: Over the course of the average 11.6±1.3-year follow-up period, enlargement of ß-zone PPA was detected in 66.7% of POAG eyes and in 26.7% of normal eyes. Increment of all PPA parameters was significantly more common in cases of POAG than in normal eyes (all P < 0.001). The spatial distribution of maximal radial extent at baseline and final examination was significantly different between the 2 groups: POAG eyes; inferotemporal versus normal eyes; temporal (chi-square = 26.549, P < 0.001, chi-square = 19.320, P = 0.004, respectively). The widening of radial extent was significantly associated with older age (OR, 1.036; P = 0.010) and the presence of glaucoma (OR, 2.599; P = 0.002). The increment of angular extent was associated with the presence of glaucoma (OR, 12.167; P = 0.017) and optic disc hemorrhage (OR, 3.266; P = 0.019). CONCLUSIONS: The pattern of ß-zone PPA change differed between POAG and normal eyes during a follow-up of 10 years or more. The enlargement of PPA occurred more frequently in POAG than in normal eyes. The widening of radial extent was associated with older age and glaucoma, whereas the increment of angular extent was associated with glaucomatous damage.

10.
Sci Rep ; 10(1): 3280, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32094401

RESUMO

We developed a hybrid deep learning model (HDLM) algorithm that quantitatively predicts macular ganglion cell-inner plexiform layer (mGCIPL) thickness from red-free retinal nerve fiber layer photographs (RNFLPs). A total of 789 pairs of RNFLPs and spectral domain-optical coherence tomography (SD-OCT) scans for 431 eyes of 259 participants (183 eyes of 114 healthy controls, 68 eyes of 46 glaucoma suspects, and 180 eyes of 99 glaucoma patients) were enrolled. An HDLM was built by combining a pre-trained deep learning network and support vector machine. The correlation coefficient and mean absolute error (MAE) between the predicted and measured mGCIPL thicknesses were calculated. The measured (OCT-based) and predicted (HDLM-based) average mGCIPL thicknesses were 73.96 ± 8.81 µm and 73.92 ± 7.36 µm, respectively (P = 0.844). The predicted mGCIPL thickness showed a strong correlation and good agreement with the measured mGCIPL thickness (Correlation coefficient r = 0.739; P < 0.001; MAE = 4.76 µm). Even when the peripapillary area (diameter: 1.5 disc diameters) was masked, the correlation (r = 0.713; P < 0.001) and agreement (MAE = 4.87 µm) were not changed significantly (P = 0.378 and 0.724, respectively). The trained HDLM algorithm showed a great capability for mGCIPL thickness prediction from RNFLPs.

11.
Korean J Ophthalmol ; 34(1): 19-26, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32037746

RESUMO

PURPOSE: We sought to compare the efficacy as well as the safety of two maximum medical therapy combinations applied to lower the intraocular pressure (IOP) in different primary open-angle glaucoma (POAG) age groups. METHODS: This was a retrospective, consecutive case series study that included 60 eyes of 60 subjects with POAG, specifically 20 subjects aged 40 to 54 years, 21 aged 55 to 69 years, and 19 aged 70 years or older. All had been treated for at least 12 months with triple maximum medical therapy (TMT; dorzolamide/timolol, brimonidine, and latanoprost) to lower their IOP, which subsequently was changed to double maximum medical therapy (DMT, fixed drug combinations of tafluprost/timolol and brinzolamide/brimonidine). The rate of IOP change and adverse drug reactions were compared amongst the three age groups. RESULTS: The mean IOP change at three months after converting from TMT to DMT was -0.65 ± 1.42 mmHg (-3.84% ± 9.31%) among the overall study group, but this finding was not statistically significant (p = 0.108). In the 40 to 54 years and 55 to 69 years groups, the mean IOP change rates were +0.29 ± 0.96 mmHg (+2.40% ± 6.85%, p = 0.087) and -0.50 ± 0.99 mmHg (-3.05% ± 6.40%, p = 0.084) respectively. In the 70 years or older group, the mean IOP change, interestingly, was -1.80 ± 1.46 mmHg (-11.29% ± 9.31%, p < 0.001) and nine (47.4%) of the 19 subjects showed additional IOP reductions of 10% or more after converting from TMT to DMT. In all three age groups, the incidence rate of dry eye was significantly lower for DMT than for TMT (p = 0.031). CONCLUSIONS: In POAG patients, DMT was proven to be both effective and safe for lowering the IOP, especially in those 70 years or older group, when compared with the TMT protocol.

12.
Br J Ophthalmol ; 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32098860

RESUMO

BACKGROUND/AIMS: To assess the performance of a deep learning classifier for differentiation of glaucomatous optic neuropathy (GON) from compressive optic neuropathy (CON) based on ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fibre layer (RNFL) spectral-domain optical coherence tomography (SD-OCT). METHODS: Eighty SD-OCT image sets from 80 eyes of 80 patients with GON along with 81 SD-OCT image sets from 54 eyes of 54 patients with CON were compiled for the study. The bottleneck features extracted from the GCIPL thickness map, GCIPL deviation map, RNFL thickness map and RNFL deviation map were used as predictors for the deep learning classifier. The area under the receiver operating characteristic curve (AUC) was calculated to validate the diagnostic performance. The AUC with the deep learning classifier was compared with those for conventional diagnostic parameters including temporal raphe sign, SD-OCT thickness profile and standard automated perimetry. RESULTS: The deep learning system achieved an AUC of 0.990 (95% CI 0.982 to 0.999) with a sensitivity of 97.9% and a specificity of 92.6% in a fivefold cross-validation testing, which was significantly larger than the AUCs with the other parameters: 0.804 (95% CI 0.737 to 0.872) with temporal raphe sign, 0.815 (95% CI 0.734 to 0.896) with superonasal GCIPL and 0.776 (95% CI 0.691 to 0.860) with superior GCIPL thicknesses (all p<0.001). CONCLUSION: The deep learning classifier can outperform the conventional diagnostic parameters for discrimination of GON and CON on SD-OCT.

13.
Jpn J Ophthalmol ; 64(3): 278-284, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32062849

RESUMO

PURPOSE: To quantitatively analyze the topographic features of localized retinal nerve fiber layer (RNFL) defects according to baseline intraocular pressure (IOP) level in cases of early primary open-angle glaucoma (POAG). STUDY DESIGN: Retrospective comparative study. METHODS: POAG patients meeting the following conditions were consecutively included: (1) baseline office-hour diurnal IOP ≤ 21 mmHg, (2) 1 localized RNFL defect as observed on red-free fundus photography, and (3) corresponding visual field defect. Defects' approximations to the macula (angle α) and width (angle ß) as well as the angle between the disc long axis and the vertical meridian line (angle Ɣ) were measured on red-free fundus photography. The corrected angle α was calculated as the difference between angles α and Ɣ. The defect area's RNFL thickness was calculated by means of optical coherence tomography's Advanced Extraction analysis utility. RESULTS: Comparative analysis was performed between 2 groups: 45 eyes of 45 patients with low-teen IOP (group A: highest IOP ≤ 15 mmHg) and 49 eyes of 49 patients with high-teen IOP (group B: lowest IOP > 15 mmHg). In group A, the mean baseline IOP was lower (12.9 ± 1.3 vs 17.1 ± 1.0 mmHg; P < .001), the corrected angle α was smaller (32.4 ± 15.1 vs 39.5 ± 13.1 degrees; P = .017), and the defect area's RNFL thickness was thinner (66.3 ± 16.8 vs 76.3 ± 14.9 µm; P = .003) than in group B; angle ß showed no intergroup difference (P = .230). CONCLUSIONS: In POAG patients with low-teen IOP relative to those with high-teen IOP, localized RNFL defects were closer to the macula. In addition, the RNFL thickness of the defect area was markedly thinner.

14.
J Glaucoma ; 29(4): 287-294, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32053552

RESUMO

PRéCIS:: A spectral-domain optical coherence tomography (SD-OCT) based deep learning system detected glaucomatous structural change with high sensitivity and specificity. It outperformed the clinical diagnostic parameters in discriminating glaucomatous eyes from healthy eyes. PURPOSE: The purpose of this study was to assess the performance of a deep learning classifier for the detection of glaucomatous change based on SD-OCT. METHODS: Three hundred fifty image sets of ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) SD-OCT for 86 glaucomatous eyes and 307 SD-OCT image sets of 196 healthy participants were recruited and split into training (197 eyes) and test (85 eyes) datasets based on a patient-wise split. The bottleneck features extracted from the GCIPL thickness map, GCIPL deviation map, RNFL thickness map, and RNFL deviation map were used as predictors for the deep learning classifier. The area under the receiver operating characteristic curve (AUC) was calculated and compared with those of conventional glaucoma diagnostic parameters including SD-OCT thickness profile and standard automated perimetry (SAP) to evaluate the accuracy of discrimination for each algorithm. RESULTS: In the test dataset, this deep learning system achieved an AUC of 0.990 [95% confidence interval (CI), 0.975-1.000] with a sensitivity of 94.7% and a specificity of 100.0%, which was significantly larger than the AUCs with all of the optical coherence tomography and SAP parameters: 0.949 (95% CI, 0.921-0.976) with average GCIPL thickness (P=0.006), 0.938 (95% CI, 0.905-0.971) with average RNFL thickness (P=0.003), and 0.889 (0.844-0.934) with mean deviation of SAP (P<0.001; DeLong test). CONCLUSION: An SD-OCT-based deep learning system can detect glaucomatous structural change with high sensitivity and specificity.

15.
Br J Ophthalmol ; 104(5): 648-654, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31395698

RESUMO

BACKGROUND: To investigate the thinning rate of three-dimensional neuroretinal rim thickness (3D-NRT) in glaucoma eyes with optic disc haemorrhage (DH) and its relationship to retinal nerve fibre layer thickness (RNFLT) progression. METHODS: Ninety-five (95) eyes of 95 glaucoma patients with initial DH in the inferotemporal (n=69) and superotemporal (n=26) regions and 48 eyes of 48 glaucoma patients without DH were retrospectively reviewed. The rates of change for 3D-NRT and RNFLT were compared by linear mixed-effect model. For the direct comparison between 3D-NRT and RNFLT, dynamic-range-based normalised coefficient was used. The effect of DH frequency on the rates of thinning of 3D-NRT and RNFLT was evaluated. RESULTS: During a mean 7-year follow-up, the rates of thinning of 3D-NRT (-5.69±4.88 µm/year) and RNFLT (-2.03±2.03 µm/year) at 7 o'clock were faster than those at other locations (all p<0.05) in DH eyes. The dynamic-range-based normalised rate of thinning was significantly faster for RNFLT (-2.06%±1.62%/year) than for 3D-NRT (-1.15%±1.10%/year, p<0.001) in DH eyes, but not in non-DH eyes (p=0.43). DH frequency in the inferotemporal region was associated with the thinning rate of 3D-NRT as well as RNFLT. CONCLUSION: DH eyes are associated with the progression of both 3D-NRT and RNFLT, especially in the inferotemporal region. DH eyes show a relatively faster thinning rate of average RNFLT than 3D-NRT. The frequency of DH can affect the progression of 3D-NRT as well as RNFLT.

16.
Br J Ophthalmol ; 104(5): 623-628, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31481393

RESUMO

BACKGROUND/AIMS: To investigate (1) the effect of reading or writing on a smartphone in terms of intraocular pressure (IOP) change in eyes with glaucoma, and (2) to determine whether previous glaucoma filtering surgery can affect IOP fluctuation during such work. METHODS: Forty eyes of 40 medically well IOP-controlled normal-tension glaucoma (NTG) patients and 38 eyes of 38 NTG patients who had undergone successful trabeculectomy (TLE) were enrolled. The participants were instructed to read a sample text and to then type it on a smartphone under low-light [100 lux] conditions. Three IOP measurements were obtained: baseline; during smartphone work (5, 15 and 25 min); post-work (5 and 15 min). RESULTS: Baseline IOP did not significantly differ between the two groups (medication group: 13.9±1.6 mm Hg; TLE group: 13.6±1.7 mm Hg; p=0.426). After 5 min of smartphone work, the medication group showed significantly elevated mean IOP (15.5±1.8 mm Hg;+11.5%; p<0.001), along with further increases over the course of 25 min (17.5±2.2 mm Hg;+25.9%; p<0.001). 5 min after halting work, IOP dropped below the baseline (13.1±1.7 mm Hg; p<0.001). For the TLE group, IOP also was elevated after 5 min (14.9±1.7 mm Hg;+9.4%; p<0.001); however, it did not show further increase over the course of 25 min of work (15.0±1.6 mm Hg;+10.3%). At 5 min after cessation of work, IOP had restored to the pre-work level (14.0±1.9 mm Hg;+2.8%; p=0.053). CONCLUSION: Working on a smartphone under low-light condition can incur IOP elevation in treated NTG patients. However, among the participants in this study, IOP fluctuation was much smaller in those who had undergone TLE.

17.
Mol Ther Nucleic Acids ; 19: 31-41, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-31790973

RESUMO

Circular RNAs (circRNAs) are generally formed by back splicing and are expressed in various cells. Vascular calcification (VC), a common complication of chronic kidney disease (CKD), is often associated with cardiovascular disease. The relationship between circRNAs and VC has not yet been studied. Inorganic phosphate (Pi) was used to treat rat vascular smooth muscle cells to induce VC. circRNAs were identified by analyzing RNA sequencing (RNA-seq) data, and their expression change during VC was validated. The selected circRNAs, including circSamd4a, circSmoc1-1, circMettl9, and circUxs1, were resistant to RNase R digestion and mostly localized in the cytoplasm. While silencing circSamd4a promoted VC, overexpressing it reduced VC in calcium assay and Alizarin red S (ARS) staining. In addition, microRNA (miRNA) microarray, luciferase reporter assay, and calcium assay suggested that circSamd4a could act as a miRNA suppressor. Our data show that circSamd4a has an anti-calcification role by functioning as a miRNA sponge. Moreover, mRNAs that can interact with miRNAs were predicted from RNA-seq and bioinformatics analysis, and the circSamd4a-miRNA-mRNA axis involved in VC was verified by luciferase reporter assay and calcium assay. Since circSamd4a is conserved in humans, it can serve as a novel therapeutic target in resolving VC.

18.
Pharmacol Res ; 152: 104615, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31881271

RESUMO

Glucagon-like peptide-1 (GLP-1) is a hormone mainly secreted from enteroendocrine L cells. GLP-1 and its receptor are also expressed in the brain. GLP-1 signaling has pivotal roles in regulating neuroinflammation and memory function, but it is unclear how GLP-1 improves memory function by regulating neuroinflammation. Here, we demonstrated that GLP-1 enhances neural structure by inhibiting lipopolysaccharide (LPS)-induced inflammation in microglia with the effects of GLP-1 itself on neurons. Inflammatory secretions of BV-2 microglia by LPS aggravated mitochondrial function and cell survival, as well as neural structure in Neuro-2a neurons. In inflammatory condition, GLP-1 suppressed the secretion of tumor necrosis factor-alpha (TNF-α)-associated cytokines and chemokines in BV-2 microglia and ultimately enhanced neurite complexity (neurite length, number of neurites from soma, and secondary branches) in Neuro-2a neurons. We confirmed that GLP-1 improves neurite complexity, dendritic spine morphogenesis, and spine development in TNF-α-treated primary cortical neurons based on altered expression levels of the factors related to neurite growth and spine morphology. Given that our data that GLP-1 itself enhances neurite complexity and spine morphology in neurons, we suggest that GLP-1 has a therapeutic potential in central nervous system diseases.

19.
Jpn J Ophthalmol ; 64(1): 68-76, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31848786

RESUMO

PURPOSE: To assess the performance of machine learning classifiers for prediction of progression of normal-tension glaucoma (NTG) in young myopic patients. STUDY DESIGN: Cross-sectional study. METHODS: One hundred and fifty-five eyes of 155 myopic NTG patients (axial length [AL] ≥ 24.00 mm and refractive error ≤ - 3.0 D) between the ages of 20 and 40 were enrolled and divided into training (110) and test (45) sets. Sixty-five eyes showed glaucoma progression as defined by standard automated perimetry, while 91 eyes (nonprogressors) had been stable over the course of a follow-up period of at least 3 years. Two machine learning classifiers were built using the random forest and extremely randomized trees (extra-trees) models. Baseline clinical measurements obtained only at the initial visit were used as input features. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the accuracy of prediction. RESULTS: Mean age and AL did not significantly differ between the 2 groups on either the training or the test set. The extra-trees model achieved an AUC of 0.881 [95% CI 0.814-0.945], higher than that of the random forest model (0.811 [0.731-0.888]; P = 0.010). The extra-trees model also outperformed all the clinical measurements for prediction of NTG progression, including average macular ganglion cell-inner plexiform layer thickness (0.735 [0.639-0.831]) and average circumpapillary retinal nerve fiber layer thickness (0.691 [0.590-0.792]; both P < 0.001). CONCLUSIONS: In young myopic patients, the machine learning classifier with the extra-trees model can predict glaucomatous progression more effectively than clinical diagnostic parameters.

20.
Br J Ophthalmol ; 104(1): 104-109, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30940619

RESUMO

BACKGROUND/AIMS: To investigate the topographic relationship between macular superficial microvessel density (SMD) and macular ganglion cell-inner plexiform layer (GCIPL) thickness in eyes with glaucoma-suspect (GS) and early normal-tension glaucoma (NTG). METHODS: A total of 86 eyes of 86 patients with early NTG (standard automated perimetry mean deviation >-5.5 decibels) and a total of 25 eyes of 25 patients with GS were retrospectively reviewed. All of the subjects underwent optical coherence tomography (OCT) and OCT angiography (OCTA) scan. On the OCTA scan images, macular SMD was analysed by customised software. RESULTS: In GS and patients with early NTG, macular GCIPL thickness showed significant correlations with macular SMD in the superotemporal (ST), inferotemporal (IT) and inferoinferior (II) sectors (r =0.191, 0.373 and 0.346 for ST, IT and II sector, respectively). Additionally, circumpapillary retinal nerve fibre layer (RNFL) thickness and macular SMD showed significant correlations between the ST sector of the macula and the 1, 9 clock-hour peripapillary regions and between the IT and II sectors of the macula and the 6, 7, 8 clock-hour peripapillary regions. The IT sector macular SMD showed fair diagnostic power (area under the receiver operating characteristic curve [AUROC] = 0.758) and showed high diagnostic power when combined with IT sector macular GCIPL thickness (AUROC=0.954). CONCLUSIONS: Sectoral macular SMD showed topographic correlations with macular GCIPL thickness and circumpapillary RNFL thickness in patients with GS and early-stage NTG. Macular SMD analysis is potentially useful in the clinical evaluation of early glaucoma.

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