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BACKGROUND AND AIMS: Previous genome-wide association studies (GWAS) have indicated the involvement of shared (population-nonspecific) and nonshared (population-specific) susceptibility genes in the pathogenesis of primary biliary cholangitis (PBC) among European and East-Asian populations. Although a meta-analysis of these distinct populations has recently identified more than 20 novel PBC susceptibility loci, analyses of population-specific genetic architecture are still needed for a more comprehensive search for genetic factors in PBC. APPROACH AND RESULTS: Protein tyrosine phosphatase nonreceptor type 2 ( PTPN2) was identified as a novel PBC susceptibility gene locus through GWAS and subsequent genome-wide meta-analysis involving 2181 cases and 2699 controls from the Japanese population (GWAS-lead variant: rs8098858, p = 2.6 × 10 -8 ). In silico and in vitro functional analyses indicated that the risk allele of rs2292758, which is a primary functional variant, decreases PTPN2 expression by disrupting Sp1 binding to the PTPN2 promoter in T follicular helper cells and plasmacytoid dendritic cells. Infiltration of PTPN2-positive T-cells and plasmacytoid dendritic cells was confirmed in the portal area of the PBC liver by immunohistochemistry. Furthermore, transcriptomic analysis of PBC-liver samples indicated the presence of a compromised negative feedback loop in vivo between PTPN2 and IFNG in patients carrying the risk allele of rs2292758. CONCLUSIONS: PTPN2 , a novel susceptibility gene for PBC in the Japanese population, may be involved in the pathogenesis of PBC through an insufficient negative feedback loop caused by the risk allele of rs2292758 in IFN-γ signaling. This suggests that PTPN2 could be a potential molecular target for PBC treatment.
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PURPOSE: To investigate the effects of 1% atropine eye drops on the choroidal thickness and structure of amblyopic and fellow eyes in children with hyperopic anisometropic amblyopia. METHODS: This study included 16 children with hypermetropic anisometropic amblyopia. All patients received 1% atropine eye drops in both eyes twice a day for 7 days. In the subfoveal choroidal region, choroidal thickness, total choroidal area, luminal area, and stromal area were measured quantitatively using swept-source optical coherence tomography. The choroidal parameters of the amblyopic and fellow eyes were compared between the baseline and atropine conditions. RESULTS: There were no significant differences in all choroidal parameters of the amblyopic eye between baseline and atropine conditions. However, the subfoveal choroidal thickness in the fellow eye was significantly higher for the atropine condition than the baseline condition. This change was accompanied by a significant increase in both the luminal and stromal areas of the choroid. The median differences of subfoveal choroidal thickness between the conditions were larger for the fellow eye (6.46%) than the amblyopic eye (0.26%). CONCLUSIONS: The choroidal structural change induced by 1% atropine instillation was smaller for the amblyopic eye than the fellow eye in children with hyperopic anisometropic amblyopia. Mechanisms of choroidal thickness changes could be inhibited in amblyopic eyes. [J Pediatr Ophthalmol Strabismus. 2023;60(1):39-45.].
Subject(s)
Amblyopia , Hyperopia , Humans , Child , Amblyopia/complications , Visual Acuity , Hyperopia/complications , Choroid , Tomography, Optical Coherence/methods , Atropine DerivativesABSTRACT
BACKGROUND: A comparison between atezolizumab plus bevacizumab (ATEZO/BEVA) and lenvatinib (LEN) for the treatment of hepatocellular carcinoma (HCC) remains unclear. OBJECTIVE: This study aimed to compare the therapeutic effects and safety of ATEZO/BEVA and LEN as first-line therapies for HCC. PATIENTS AND METHODS: This study was a retrospective analysis of 810 patients with HCC who underwent ATEZO/BEVA (n = 186) or LEN (n = 624) as first-line systemic therapy between March 2018 to March 2022 at 14 facilities. After propensity score matching, 304 patients (ATEZO/BEVA group: n = 152; LEN group: n = 152) were analyzed. RESULTS: After propensity score matching, although there was no significant difference in objective response rates (ORRs) between the ATEZO/BEVA and LEN groups (ORR 44.8% vs. 46.7%, p = 0.644), the median progression-free survival (PFS) and median overall survival (OS) in the ATEZO/BEVA group were significantly higher than those in the LEN group (median PFS: 8.3 months vs. 6.0 months, p = 0.005; median OS: not reached vs. 20.2 months, p = 0.039). The rates of appetite loss, fatigue, and proteinuria of grade 3 or higher in the ATEZO/BEVA group were lower than those in the LEN group. However, the rate of bleeding of grade 3 or higher in the ATEZO/BEVA group was higher than that in the LEN group. The conversion rate was higher in the ATEZO/BEVA group than that in the LEN group (8.6% vs. 1.9%, p = 0.007). CONCLUSIONS: ATEZO/BEVA showed superiority to LEN in terms of prognosis and conversion rate as first-line therapy. Moreover, ATEZO/BEVA had a lower rate of severe adverse events, except for bleeding, than LEN.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Bevacizumab/pharmacology , Bevacizumab/therapeutic use , Liver Neoplasms/pathology , Propensity Score , Retrospective StudiesABSTRACT
Electroretinography (ERG) is used to evaluate the physiological status of the retina and optic nerve. The purpose of this study was to determine the usefulness of ERGs recorded with the RETeval system in diagnosing optic nerve diseases. Forty-eight patients with optic nerve disorders, including optic neuritis, ischemic optic neuropathy, traumatic optic neuropathy, and dominant optic atrophy, and 36 normal control subjects were studied. The amplitudes of the photopic negative response (PhNR) were recorded with the RETeval system without mydriasis. The circumpapillary retinal nerve fiber layer thickness (cpRNFLT) was determined by optical coherence tomography (OCT). The significance of the correlations between the PhNR and cpRNFLT parameters were determined, and the receiver operating curve (ROC) analyses were performed for the PhNR and cpRNFLT. Patients with optic nerve disorders had significantly smaller PhNRs compared to the control subjects (P = 0.001). The ROC analyses indicated that both PhNR and cpRNFLT had comparable diagnostic abilities of detecting optic nerve disorders with PhNR at 0.857 and cpRNFLT at 0.764. The PhNR components recorded with the RETeval system have comparable diagnostic abilities as the cpRNFLT in diagnosing optic nerve disorders.
Subject(s)
Color Vision , Optic Nerve Diseases , Electroretinography/methods , Humans , Optic Nerve/diagnostic imaging , Optic Nerve Diseases/diagnostic imaging , Tomography, Optical Coherence/methodsABSTRACT
We examined the epidemiological trends, including the distribution of sex, age, and disease etiology, in HCC incident cases, over 24 years. Data of 20,547 HCC patients (1996-2019) were analyzed in this prospective study. We divided the study period into four 6-yearly quarters. HCC etiology was categorized as hepatitis B virus (HBV) infection, HBV + hepatitis C virus (HCV) infection, HCV infection, and both negative (non-BC). The incident cases of HCC per quarter of the study period were 4311 (21.0%), 5505 (26.8%), 5776 (28.1%), and 4955 (24.1%), sequentially. Overall, 14,020 (68.2%) patients were male. The number of HCC cases in patients < 60 years, 60-69 years, 70-79 years, and ≥ 80 years were 3711 (18.1%), 6652 (32.4%), 7448 (36.2%), and 2736 (13.3%), respectively. The average age of newly-diagnosed patients increased in each quarter. HCC was associated with HBV, HBV + HCV, and HCV infections and non-BC in 2997 (14.6%), 187 (0.9%), and 12,019 (58.5%), and 5344 (26.0%) cases, respectively. The number of HCV-associated cases decreased in each quarter, while that of non-BC-associated cases increased. HCC incident cases tend to increase in the elderly and in non-BC patients; in contrast, HCC incident cases due to HCV tend to decrease.
Subject(s)
Carcinoma, HepatocellularABSTRACT
AIM: Despite advances in the management of liver diseases and changes in the etiology of cirrhosis, few studies have updated the prognosis of cirrhosis. This study aimed to clarify the recent prognosis of cirrhosis and identify risk factors for death. METHODS: In this retrospective observational study by the Hepatic Disease Network of the National Hospital Organization in Japan, chart reviews were performed to follow patients with cirrhosis beginning in 2011. We conducted Kaplan-Meier survival time analyses stratified by Child-Pugh classification and albumin-bilirubin grade. Cox regression analysis was used to identify risk factors for death. RESULTS: We identified 444 eligible patients from 25 hospitals, including 303 (68%), 110 (25%), and 31 (7%) patients with Child-Pugh classes A, B, and C, respectively. Hepatitis C virus infection was the cause of cirrhosis for 63% of the patients. The 1-year and 5-year cumulative survival rates of patients with Child-Pugh classes A, B, and C were 90% and 61%, 78% and 42%, and 65% and 25%, respectively. The 1-year and 5-year cumulative survival rates of patients with albumin-bilirubin grades 1, 2, and 3 were 98% and 80%, 91% and 56%, and 58% and 23%, respectively. Cirrhosis classification (Child-Pugh and albumin-bilirubin), age, liver cancer, and untreated esophageal varices were associated with increased hazard of death. CONCLUSIONS: Little improvement was observed in the prognosis of cirrhosis compared with previous reports, and the prognosis of Child-Pugh class C cirrhosis remained poor. Untreated esophageal varices were identified as a risk factor for death.
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Purpose: Soft contact lenses (SCLs) are effective for refractive error correction, but prolonged wear triggers discomfort and discontinuation. This study investigates whether water gradient technology of delefilcon A-based SCLs improve tear film dynamics. Methods: This retrospective observational study included 50 asymptomatic delefilcon A or narafilcon A users. Data on thin aqueous layer break (TALB; %), noninvasive tear break-up time (NIBUT), tear meniscus height (TMH; mm), subjective dryness, and higher-order aberrations (HOAs) were collected. Measurements of the bare eye, the SCL-worn eye after 15 minutes (visit 1 [v1]) and 30 ± 5 days after v1 after SCL was worn for ≥5 hours (visit 2 [v2]) were recorded. Results: TALB was significantly reduced in the delefilcon A group compared to the narafilcon A group (33.3% vs. 85.5% at v1; P < 0.0001 and 31.7% vs. 80.4% at v2; P < 0.0001). The NIBUT was also significantly higher in the former (4.2 ± 2.1 seconds vs. 2.9 ± 1.5 at v1; P < 0.01 and 4.1 ± 2.3 seconds vs. 2.7 ± 1.6 seconds at v2; P < 0.01) across both visits. The TMH was significantly reduced in the former in both v1 and v2. The total ocular HOAs were significantly lower in the former at v1 (P < 0.001) and v2 (P < 0.05) compared to the bare eye. Conclusions: The water gradient technology of delefilcon A reduces TALB and increases NIBUT. Translational Relevance: The use of water gradient technology improves tear film dynamics and alleviate pathological break-up pattern, improving lens performance.
Subject(s)
Contact Lenses, Hydrophilic , Silicones , Hydrogels , Tears , WaterABSTRACT
BACKGROUND: Structural changes of the choroid, such as choroidal thickening, have been indicated in amblyopic eyes with hyperopic anisometropia as compared to fellow or healthy eyes. The purpose of the present study was to investigate choroidal vascular density (CVD) in children with unilateral hyperopic amblyopia. METHODS: This study included 88 eyes of 44 patients with unilateral amblyopia due to hyperopic anisometropia with or without strabismus and 29 eyes of 29 age-matched normal controls. The CVD of Haller's layer was quantified from en-face images constructed by 3-dimensional swept-source optical coherence tomography images flattened relative to Bruch's membrane. The analysis area was a 3 × 3-mm square of macula after magnification correction. Relationships between CVD and other parameters [best-corrected visual acuity (BCVA), refractive error and subfoveal choroidal thickness (SFCT)] were investigated, and CVDs were compared between amblyopic, fellow, and normal control eyes. RESULTS: Mean CVD was 59.11 ± 0.66% in amblyopic eyes, 59.23 ± 0.81% in fellow eyes, and 59.29 ± 0.74% in normal control eyes. CVD showed a significant positive relationship with SFCT (p = 0.004), but no relationships with other parameters. No significant differences in CVD were evident among amblyopic, fellow, and normal control eyes after adjusting for SFCT (p = 0.502). CONCLUSIONS: CVD was unrelated to BCVA, and CVD did not differ significantly among amblyopic, fellow and normal control eyes. These results suggest that the local CVD of Haller's layer is unaffected in unilateral hyperopic amblyopic eyes.
Subject(s)
Amblyopia , Hyperopia , Child , Choroid , Humans , Tomography, Optical Coherence , Visual AcuityABSTRACT
The present study was performed to evaluate the ganglion cell complex (GCC) thickness as well as the significance map and analyse the time course of the change in GCC thickness in patients with homonymous hemianopia due to posterior cerebral artery (PCA) territory stroke using spectral-domain optical coherence tomography. This study included 40 control subjects and 11 patients with unilateral PCA territory stroke. The GCC parameters were quantified using a custom-built software programme. The GCC data, centred on the macula, was divided vertically into hemianopic and unaffected sides. GCC parameters were calculated using an average of those from both eyes. The relationship between the GCC parameters and the time after stroke was determined by regression analyses. The GCC parameters in the hemi-retinae corresponding to the affected hemifields significantly differed between the hemianopes and the control group. The area under the receiver operating characteristics curve of the GCC significance map areas was significantly high. A regression analysis revealed a significant relationship between the time after stroke and both the GCC significance map areas (r = 0.791, p = .004) and GCC thickness (r = -0.736, p = .010) on the hemianopic side. The GCC parameters on the hemianopic side were reduced in patients with acquired occipital homonymous hemianopia, and the reduction was slowly progressive probably due to transsynaptic retrograde degeneration of the retinal ganglion cells. A significance map analysis provides additional OCT parameters that could be used to investigate the effect of retrogeniculate lesions on the inner retina of patients.
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BACKGROUND AND OBJECTIVES: Atherosclerosis is characterized by a hypercoagulable state, during which coagulation and fibrinolytic factors are activated simultaneously. However, details regarding the thrombolytic pathway in this context remain unknown. Here we investigated how direct long-term inhibition of thrombin influenced spontaneous thrombolytic activity during atherosclerotic progression in apolipoprotein E (ApoE)â»/â»-low density lipoprotein receptor (LDLR)â»/â» double-knockout mice. METHODS: All mice received either standard chow (placebo group) or dabigatran-containing chow for 22 weeks, after which we evaluated them. The amount of atherosclerosis was estimated as the ratio of the atherosclerotic area to the total aortic intimal area. In addition, we used immunohistochemistry to analyze the expression of tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), and endothelial nitric oxide synthase (eNOS) in atherosclerotic regions. To evaluate thrombolysis, we used a He-Ne laser to induce thrombosis in vessels of the cremaster muscle and then measured the thrombus volume over time. RESULTS: The atherosclerotic area was smaller and thrombolytic activity greater in the dabigatran-treated group than in the placebo group. Furthermore, according to the thrombolysis model, spontaneous thrombolytic activity was increased in the dabigatran-treated mice compared with the placebo mice. In support of these results, immunohistochemistry demonstrated decreased expression of PAI-1 and TAFI but increased expression of eNOS in the dabigatran group compared with the placebo group. However, t-PA expression did not differ between groups. CONCLUSIONS: Direct long-term inhibition by dabigatran etexilate of thrombin led to an increase in spontaneous thrombolytic activity decreasing the expression of PAI-1 and TAFI.
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BACKGROUND: To investigate the area of foveal avascular zone (FAZ) and macular vessel density (VD) after correction for magnification error in unilateral amblyopia using optical coherence tomography angiography (OCTA). METHODS: Participants comprised 15 patients with unilateral amblyopia due to anisometropia with or without strabismus (mean age, 9.8 ± 3.4 years; range, 6-17 years). OCTA images were obtained by using spectral-domain OCT with angiography software. The OCTA scanning protocol used was 3 × 3-mm volume scan centered on the fovea. OCTA images were corrected for magnification errors using individual axial length (AL), and an adjusted 2.3 × 2.3-mm square was derived as a region of interest. The FAZ area and VD in both superficial capillary plexus (SCP) and deep capillary plexus (DCP) layers, foveal minimum thickness (FMT) were assessed using built-in OCTA software and ImageJ software (NIH, Bethesda, MD). RESULTS: LogMAR in the amblyopic eyes was significantly poorer than that of the fellow eye (p < 0.001). AL was significantly shorter in the amblyopic eye than in the fellow eye (p < 0.001). FAZ area of SCP in amblyopic eyes was significantly smaller than that of fellow eyes (p < 0.001). No significant differences were seen in FAZ area of DCP, VD of SCP, VD of DCP, and FMT between amblyopic and fellow eyes (p = 0.07, 0.43, 0.55, and 0.25, respectively). CONCLUSIONS: Our present study after magnification error correction found smaller FAZ area of SCP in the amblyopic eye compared with the fellow eyes, but there was no significant difference in the macular VD between the amblyopic and fellow eyes.
Subject(s)
Amblyopia/diagnosis , Fluorescein Angiography/methods , Macula Lutea/blood supply , Retinal Vessels/pathology , Tomography, Optical Coherence/methods , Visual Acuity , Adolescent , Amblyopia/physiopathology , Capillaries/pathology , Child , Cross-Sectional Studies , Female , Fovea Centralis , Fundus Oculi , Humans , Macula Lutea/diagnostic imaging , Male , Retrospective StudiesABSTRACT
Primary biliary cholangitis (PBC) is a chronic and cholestatic autoimmune liver disease caused by the destruction of intrahepatic small bile ducts. Our previous genome-wide association study (GWAS) identified six susceptibility loci for PBC. Here, in order to further elucidate the genetic architecture of PBC, a GWAS was performed on an additional independent sample set, then a genome-wide meta-analysis with our previous GWAS was performed based on a whole-genome single nucleotide polymorphism (SNP) imputation analysis of a total of 4,045 Japanese individuals (2,060 cases and 1,985 healthy controls). A susceptibility locus on chromosome 3q13.33 (including ARHGAP31, TMEM39A, POGLUT1, TIMMDC1, and CD80) was previously identified both in the European and Chinese populations and was replicated in the Japanese population (OR = 0.7241, P = 3.5 × 10-9). Subsequent in silico and in vitro functional analyses identified rs2293370, previously reported as the top-hit SNP in this locus in the European population, as the primary functional SNP. Moreover, e-QTL analysis indicated that the effector gene of rs2293370 was Protein O-Glucosyltransferase 1 (POGLUT1) (P = 3.4 × 10-8). This is the first study to demonstrate that POGLUT1 and not CD80 is the effector gene regulated by the primary functional SNP rs2293370, and that increased expression of POGLUT1 might be involved in the pathogenesis of PBC.
Subject(s)
Glucosyltransferases/genetics , Liver Cirrhosis, Biliary/genetics , Polymorphism, Single Nucleotide , Adult , Aged , Aged, 80 and over , Female , Genome-Wide Association Study , Humans , Japan , Male , Middle Aged , Young AdultABSTRACT
In a patient with an optic tract syndrome, we describe the loss of retinal nerve fiber layer and retinal microvasculature using enface and optical coherence tomography angiography image analyses.
Subject(s)
Nerve Fibers/pathology , Optic Disk/blood supply , Optic Nerve Diseases/pathology , Optic Tract/pathology , Retinal Ganglion Cells/pathology , Retinal Vessels/pathology , Tomography, Optical Coherence , Adult , Capillaries/diagnostic imaging , Capillaries/pathology , Fluorescein Angiography , Humans , Intraocular Pressure , Male , Optic Disk/diagnostic imaging , Optic Nerve Diseases/diagnostic imaging , Optic Tract/diagnostic imaging , Retinal Vessels/diagnostic imaging , Visual FieldsABSTRACT
BACKGROUND: Recent studies using optical coherence tomography (OCT) have indicated that choroidal thickness (CT) in the anisometropic amblyopic eye is thicker than that of the fellow and normal control eyes. However, it has not yet been established as to how amblyopia affects the choroid thickening. The purpose of the present study was to investigate the effect of amblyopia treatment on macular CT in eyes with anisometropic amblyopia using swept-source OCT. METHODS: Thirteen patients (mean age: 6.2 ± 2.4 years) with hypermetropic anisometropic amblyopia were included in this study. Visual acuity (VA), axial length (AL), and CT were measured at the enrollment visit and at the final visit, after at least 6 months of treatment. CT measurements were corrected for magnification error and were automatically analyzed using built-in software and divided into three macular regions (subfoveal choroidal thickness (SFCT), center 1 mm, and center 6 mm). A one-way analysis of covariance using AL as a covariate was performed to determine whether CT in amblyopic eyes changed after amblyopia treatment. RESULTS: The average observation period was 22.2 ± 11.0 months. After treatment, VA (logMAR) improvement in the amblyopic eyes was 0.41 ± 0.19 (p < 0.001). SFCT, center 1 mm CT, and center 6 mm CT were significantly thicker in the amblyopic eyes compared with the fellow eyes both before and after treatment (p < 0.05 for all comparisons). There were no significant changes in SFCT, center 1 mm CT, or center 6 mm CT before and after treatment in the amblyopic (p = 0.25, 0.21, and 0.84, respectively) and fellow (p = 0.75, 0.84, and 0.91, respectively) eyes. The correlation between changes in logMAR versus changes in CT after treatment was not significant. CONCLUSIONS: Although VA in amblyopic eyes was significantly improved after treatment, the choroid thickening of anisometropic amblyopic eyes persisted, and there was no significant change found in the CT after the treatment. Our findings suggest that thickening of the CT in amblyopia is not directly related to visual dysfunction.
Subject(s)
Amblyopia/therapy , Choroid/pathology , Hyperopia/therapy , Refraction, Ocular , Tomography, Optical Coherence/methods , Visual Acuity , Amblyopia/complications , Amblyopia/physiopathology , Child , Child, Preschool , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Hyperopia/complications , Hyperopia/physiopathology , Male , Retrospective Studies , Sensory DeprivationABSTRACT
Relative afferent pupillary defects (RAPD) may be detected in patients with occipital lobe lesions. However, no previous report has used an objective technique to record the abnormal pupillary light reflex in such cases. Therefore, we measured the pupillary light reflex objectively in 15 patients with homonymous visual field defects (HVFD) due to occipital stroke using a new pupillometer. This study detected significantly smaller and slower pupillary light reflexes in the contralateral eyes than in the other eyes, which is equivalent to the presence of RAPD in patients with HVFDs caused by retrogeniculate lesions using an objective technique. Our results confirmed those of the previous reports using the swinging flashlight test more objectively.
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AIMS: PCR-Invader is a highly sensitive assay for detecting non-structural protein 5A (NS5A) resistance-associated variants (RAVs) of hepatitis C virus (HCV). Here, we validated the accuracy of the semiquantitative PCR-Invader (SQ-PI) assay compared to direct sequencing (DS) for identifying NS5A RAVs, and we evaluated the treatment efficacy of daclatasvir plus asunaprevir (DCV + ASV) for patients judged to be non-positive for NS5A RAVs by SQ-PI. METHODS: Detection rates of NS5A RAVs by SQ-PI and DS were compared for 204 patients with HCV genotype 1b. Patients with non-positive results for NS5A RAVs by SQ-PI were treated by DCV + ASV, and the efficacy of this treatment was examined. RESULTS: All samples judged as negative for NS5A RAVs by SQ-PI were similarly judged by DS. However, 29.7% of samples judged as negative for Y93H by DS were judged as weakly positive or positive by SQ-PI. Among 108 patients who were judged as negative by SQ-PI and treated by DCV + ASV, rates of sustained virologic response at 24 weeks (SVR24) were 96.3% in intention-to-treat analysis and 99.0% in patients who completed treatment. Among patients who were weakly positive for Y93H on SQ-PI, the SVR24 rate was 95.0% (19/20). This rate was 100% (78/78) in patients who were negative for Y93H on SQ-PI and completed treatment. CONCLUSION: Treatment efficacy of DCV + ASV was extremely high among patients who were non-positive for NS5A RAVs on SQ-PI, especially for patients with negative results.
Subject(s)
Brain Diseases/complications , Geniculate Bodies/pathology , Hemianopsia/diagnosis , Nerve Fibers/pathology , Retinal Ganglion Cells/pathology , Adult , Aged , Aged, 80 and over , Atrophy , Brain Diseases/diagnostic imaging , Female , Geniculate Bodies/diagnostic imaging , Hemianopsia/etiology , Humans , Male , Middle Aged , Tomography, Optical Coherence , Young AdultABSTRACT
BACKGROUND: Atherosclerosis is characterized by a hypercoagulable state, during which both coagulation and thrombolytic factors are activated simultaneously. However, details regarding the thrombolytic pathway in this context remain unknown. Here we investigated the changes in spontaneous thrombolytic activity during atherosclerotic progression in Apo-/-LDLR-/- double-knockout mice (DKO group). METHODS: We fed DKO mice and their controls (C57Bl6 mice) a high-fat diet for a total of 22 weeks and evaluated them at 14 and 22 weeks. The amount of atherosclerosis was estimated as the ratio of the atherosclerotic to total aortic intimal area. In addition, we used immunohistochemistry to analyze the expression of PAI-1, t-PA, and eNOS in atherosclerotic regions. To evaluate thrombolysis, we used a He-Ne laser to induce thrombosis in vessels of the cremaster muscle and then measured the thrombus volume over time. RESULTS: The atherosclerotic area was increased and thrombolytic activity was decreased in DKO group compared with the control group. Furthermore, the plasma PAI-1 level was 3 times greater in the DKO group than in the control group. In support of these results, immunohistochemistry showed increased PAI-1 expression in the DKO group, whereas t-PA and eNOS expression was greater in the control group. CONCLUSION: Progression of atherosclerosis led to a reduction in thrombolytic activity through decreases in t-PA and eNOS levels and an increase in PAI-1 production. These findings indicate that decreases in factors that promote spontaneous thrombolytic activity may indicate increased risk for the progression of atherosclerosis.
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BACKGROUND: To investigate macular retinal and choroidal thickness in amblyopic eyes compared to that in fellow and normal eyes using swept-source optical coherence tomography (SS-OCT). METHODS: This study examined 31 patients with hyperopic anisometropic amblyopia (6.9 ± 3.8 years, mean ± standard deviation), 15 patients with strabismic amblyopia without anisometropia (7.9 ± 4.2 years), and 24 age-matched controls (7.8 ± 3.3 years). Retinal and choroidal thickness was measured by 3D scans using SS-OCT. A 6-mm area around the fovea was automatically analyzed using the Early Treatment Diabetic Retinopathy Study map. The thickness from SS-OCT was corrected for magnification error using individual axial length, spherical refraction, cylinder refraction, and corneal radius. Retinal thickness was divided into the macular retinal nerve fiber layer (mRNFL), ganglion cell layer + inner plexiform layer (GCL+IPL), ganglion cell complex (GCC), and the inner limiting membrane to the retinal pigment epithelium (ILM-RPE) thickness. Retinal and choroidal thickness was compared among amblyopic, fellow, and normal eyes. RESULTS: In both amblyopia groups, there was no significant difference in the mRNFL, GCL+IPL, and GCC thicknesses among the amblyopic, fellow, and control eyes. In the anisometropic amblyopia group, choroidal thickness (subfovea, center 1 mm, nasal and inferior of the inner ring, nasal of the outer ring, and center 6 mm) of amblyopic eyes were significantly greater than that of fellow and normal eyes. In contrast, none of the choroidal thicknesses were significantly different among the investigated eyes in the strabismic amblyopia group. CONCLUSIONS: We found no significant difference in inner retinal thickness in patients with unilateral amblyopia. Although there were significant differences in choroidal thickness with hyperopic anisometropic amblyopia, there was no significant difference for the strabismic amblyopia. The discrepancy in choroidal thickness between the two types of amblyopia may be due to both differences in ocular size and underlying mechanism.
Subject(s)
Amblyopia/pathology , Choroid/pathology , Macula Lutea/pathology , Adolescent , Adult , Analysis of Variance , Case-Control Studies , Child , Child, Preschool , Female , Humans , Male , Nerve Fibers/pathology , Retinal Ganglion Cells/pathology , Tomography, Optical Coherence/methods , Young AdultABSTRACT
OBJECTIVE: To evaluate macular inner retinal layers using swept-source optical coherence tomography (SS-OCT) in patients with homonymous hemianopia due to optic tract syndrome (OTS). METHODS: Sixteen eyes of 8 patients with OTS were studied. The macular retinal nerve fiber layer (mRNFL), ganglion cell layer and inner plexiform layer (GCL + IPL), and mRNFL and GCL + IPL (GCC) were measured by SS-OCT (DRI OCT-1 Atlantis®).The scanned area was divided into eight regions and two hemiretinae. Each retinal thickness of the OTS group was compared with that of the 25 control subjects. RESULTS: The GCC thickness in the ipsilateral eyes was significantly reduced in all regions, although predominant thinning of the GCC in the contralateral eyes was found in the nasal region. The GCC + IPL thickness was preferentially reduced at the temporal regions in the ipsilateral eyes and at the nasal regions in the contralateral eyes. The reduction rate of the GCL + IPL thickness was 29.6% at the temporal hemiretina in the ipsilateral eyes and 35.2% at the nasal hemiretina in the contralateral eyes. CONCLUSION: We found preferential loss of the GCC + IPL thickness corresponding to the hemifield defects in each eye. Quantitative analysis by SS-OCT is capable of detecting the characteristic RGC loss due to OTS.