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Purpose: To investigate the association of systemic oxidative stress level with myopic choroidal neovascularization (mCNV) and its clinical outcomes. Design: Retrospective case-control study. Participants: This retrospective study included 52 eyes of 52 healthy participants (mean age: 62.5 years), 30 eyes of 30 patients (mean age: 59.6 years) with high myopia (HM) but without mCNV, and 23 eyes of 23 patients (mean age: 61.8 years) with HM and mCNV who received intravitreal anti-VEGF antibody injections (IVIs) using a pro re nata regimen during the 6-month follow-up after the first IVI. Methods: Clinical findings, including oxidative stress parameters, such as diacron reactive oxygen metabolites (dROMs), biological antioxidant potential (BAP), and the BAP/dROM ratio (B/d ratio), were analyzed. Main Outcome Measures: Clinical features and oxidative stress parameters. Results: Both BAP and the B/d ratio were significantly lower in the HM/mCNV group than in the HM/no mCNV group (P = 0.002 and P = 0.012, respectively) and than in the control group (P = 0.001 and P = 0.026, respectively). In a multiple logistic regression analysis, axial length (odds ratio 1.878, P = 0.042) and the B/d ratio (odds ratio 0.470, P = 0.026) were significantly associated with mCNV. Dividing the patients into high and low B/d ratio groups (with a cutoff of 5.2) showed that subfoveal choroidal thickness (SFCT) was lower (P = 0.002) and the number of IVI treatments was higher (P = 0.029) in the low B/d ratio group than in the high B/d ratio group. In multiple regression analyses, only the B/d ratio was significantly associated with SFCT (ß = 0.684, P = 0.006). Conclusions: The oxidative stress level in eyes with HM differed according to mCNV, SFCT, and the number of IVI treatments. Measuring oxidative stress parameters might be useful in eyes with HM both for assessing the risk of developing mCNV and determining disease activity. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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PURPOSE: To compare blood flow (BF) impairment patterns in different optic neuropathies using laser speckle flowgraphy (LSFG). METHODS: This retrospective study enrolled 24 eyes of 24 patients with non-arteritic anterior ischemic optic neuropathy (NAAION), 59 eyes of 59 patients with optic neuritis (ON), 677 eyes of 677 patients with open-angle glaucoma (OAG), and 110 eyes of 110 controls. The patient backgrounds of all groups were compared. Ophthalmologic findings were evaluated, adjusting for age, sex, blood pressure, pulse rate, and underlying systemic diseases with 1:1 optimal propensity score matching. We used LSFG to obtain optic nerve head (ONH) vessel-area mean blur rate (MBR; ONH-MV), ONH tissue-area MBR (ONH-MT), and choroidal MBR. The NAAION and ON groups were compared with the control and OAG groups. RESULTS: Best-corrected visual acuity was worse in the NAAION, ON, and OAG groups than in controls (p < 0.001). Circumpapillary retinal nerve fibre layer thickness was higher in the NAAION and ON groups and lower in the OAG group than in controls (p < 0.001). Compared to controls, the NAAION and OAG groups had significantly lower ONH-MV, ONH-MT, and choroidal MBR (p < 0.05). Additionally, the NAAION group had lower ONH-MV and choroidal MBR than the OAG group (p = 0.003 and p < 0.001, respectively) but no difference in ONH-MT (p = 0.857). The ON group had significantly lower ONH-MV and choroidal MBR compared to the controls (p < 0.001 and p = 0.022, respectively) but no difference in ONH-MT (p = 0.773). CONCLUSION: Optic neuropathies showed different patterns of ocular BF impairment. Therefore, LSFG can be a useful tool for differentiating optic neuropathies.
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PURPOSE: Equol is metabolized by intestinal bacteria from soy isoflavones and is chemically similar to estrogen. Dietary habits, such as consumption of soy products, influence equol production. A relationship between glaucoma and estrogen has been identified; here, we investigated the relationship between equol production status and glaucoma in Japan. METHODS: We recruited 68 normal-tension glaucoma (NTG) patients (male to female ratio 26:42, average age 63.0 ± 7.6 years) and 31 controls (male to female ratio 13:18, average age 66.0 ± 6.3 years) from our hospital. All women included were postmenopausal. Urinary equol concentration was quantified with the ELISA method. MD was calculated based on the Humphrey visual field. The association between MD and equol was analyzed with Spearman's rank correlation coefficient. The Mann-Whitney U test was used to compare the equol-producing (> 1 µM) and non-producing (< 1 µM) subjects. We also investigated the association between equol and glaucoma with a logistic regression analysis. RESULTS: There was a significant association between equol and MD (r = 0.36, P < 0.01) in the NTG patients. Glaucoma, represented by MD, was significantly milder in the equol-producing subjects than the non-equol producing subjects (P = 0.03). A multivariate analysis revealed the independent contributions of equol, cpRNFLT, and IOP to MD (P = 0.03, P = 0.04, and P < 0.01, respectively). CONCLUSION: Our results suggest that equol, acting through estrogen receptor-mediated neuroprotective effects, might be involved in suppressing the progression of NTG. This result also adds to evidence that glaucoma may be influenced by lifestyle.
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Equol , Presión Intraocular , Glaucoma de Baja Tensión , Humanos , Glaucoma de Baja Tensión/metabolismo , Glaucoma de Baja Tensión/fisiopatología , Femenino , Persona de Mediana Edad , Anciano , Masculino , Equol/metabolismo , Equol/biosíntesis , Presión Intraocular/fisiología , Campos Visuales/fisiología , Japón/epidemiología , Ensayo de Inmunoadsorción EnzimáticaRESUMEN
Purpose: Timely detection and treatment of visual impairments and age-related eye diseases are essential for maintaining a longer, healthier life. However, the shortage of appropriate medical equipment often impedes early detection. We have developed a portable self-imaging slit-light device utilizing NIR light and a scanning mirror. The objective of our study is to assess the accuracy and compare the performance of our device with conventional nonportable slit-lamp microscopes and anterior segment optical coherence tomography (AS-OCT) for screening and remotely diagnosing eye diseases, such as cataracts and glaucoma, outside of an eye clinic. Approach: The NIR light provides an advantage as measurements are nonmydriatic and less traumatic for patients. A cross-sectional study involving Japanese adults was conducted. Cataract evaluation was performed using photographs captured by the device. Van-Herick grading was assessed by the ratio of peripheral anterior chamber depth to peripheral corneal thickness, in addition to the iridocorneal angle using Image J software. Results: The correlation coefficient between values obtained by AS-OCT, and our fabricated portable scanning slit-light device was notably high. The results indicate that our portable device is equally reliable as the conventional nonportable slit-lamp microscope and AS-OCT for screening and evaluating eye diseases. Conclusions: Our fabricated device matches the functionality of the traditional slit lamp, offering a cost-effective and portable solution. Ideal for remote locations, healthcare facilities, or areas affected by disasters, our scanning slit-light device can provide easy access to initial eye examinations and supports digital eye healthcare initiatives.
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Purpose: To investigate clinical factors associated with foveal avascular zone (FAZ) parameters obtained using OCT angiography (OCTA) with assistance from a previously developed artificial intelligence (AI) platform in eyes with open-angle glaucoma (OAG). Design: Retrospective longitudinal. Participants: This study followed up 885 eyes of 558 patients with OAG for ≥ 2 years; all eyes underwent ≥ 5 Humphrey visual-field (VF) tests and had 3.0 × 3.0 mm macular OCTA scans available. Methods: Average total deviation (TD) in the superior, superocentral, inferocentral, and inferior sectors of the Humphrey 24-2 program was calculated. We collected 3.0 × 3.0 mm macular OCTA images from each patient and used a previously developed AI platform with these images to obtain FAZ parameters, including FAZ area, FAZ circularity index (CI), and FAZ perimeter. Multivariable linear mixed-effects models were used to analyze the relationship between FAZ parameters, TD or TD slope in each quadrant, and systemic factors, adjusting for potential confounding factors, including axial length. Main Outcome Measures: Ophthalmic and systemic variables, FAZ parameters, and TD or TD slope in each quadrant. Results: The multivariable model showed that FAZ parameters were correlated with both TD and TD slope in the inferocentral quadrant (ß = -0.244 - 0.168, P < 0.001). Both upper-half and lower-half FAZ parameters were better associated with TD-inferocentral and TD-inferocentral slope than TD-superocentral or TD-superocentral slope in terms of ß size and statistical significance, indicating that there was no evident vertical anatomical correspondence between TD in the central quadrant and FAZ parameters. Foveal avascular zone area enlargement was associated with female gender (ß = 0.242, P = 0.003). Loss of FAZ circularity was associated with both aging and comorbid sleep apnea syndrome (SAS) (yes: 1, no: 0) (ß = -0.188, P < 0.001; ß = -0.261, P = 0.031, respectively). Foveal avascular zone perimeter elongation was associated with aging and female gender (ß = 0.084, P = 0.040; ß = 0.168, P = 0.042, respectively). Conclusions: Artificial intelligence-assisted OCTA-measured FAZ enlargement and irregular shape might be good markers of ocular hypoperfusion and associated inferocentral VF defect progression in eyes with OAG. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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PURPOSE: To investigate sectoral differences in the relationship between intraocular pressure (IOP) dynamics during dark-room prone testing (DRPT) and visual field (VF) defect progression in primary open-angle glaucoma (POAG) patients. DESIGN: Retrospective, longitudinal study. PARTICIPANTS: This retrospective study included 116 eyes of 84 POAG patients who underwent DRPT and had at least 5 reliable VF tests conducted over a more than 2-year follow-up period. We excluded eyes with mean deviation worse than -20 dB or a history of intraocular surgery or laser treatment. METHODS: Average total deviation (TD) was calculated in the superior, central, and inferior sectors of the Humphrey 24-2 or 30-2 program. During DRPT, IOP was measured in the sitting position, and after 60 minutes in the prone position in a dark room, IOP was measured again. The relationship between IOP change during DRPT, IOP after DRPT, and TD slope in each quadrant was analyzed with a linear mixed-effects model, adjusting for other potential confounding factors. MAIN OUTCOME MEASURES: Total deviation slope in each quadrant, IOP change during DRPT, and IOP after DRPT. RESULTS: Intraocular pressure after DRPT and IOP change during DRPT were 18.16 ± 3.42 mmHg and 4.92 ± 3.12 mmHg, respectively. Superior TD slope was significantly associated with both IOP after DRPT (ß = -0.28, P = 0.003) and IOP change during DRPT (ß = -0.21, P = 0.029), while central (ß = -0.05, P = 0.595; ß = -0.05; P = 0.622) and inferior (ß = 0.05, P = 0.611; ß = 0.01, P = 0.938) TD slopes were not. CONCLUSION: Dark-room prone testing might be a useful test to predict the risk of superior VF defect progression in eyes with POAG. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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Progresión de la Enfermedad , Glaucoma de Ángulo Abierto , Presión Intraocular , Campos Visuales , Humanos , Presión Intraocular/fisiología , Campos Visuales/fisiología , Estudios Retrospectivos , Masculino , Femenino , Glaucoma de Ángulo Abierto/fisiopatología , Glaucoma de Ángulo Abierto/diagnóstico , Persona de Mediana Edad , Anciano , Estudios de Seguimiento , Pruebas del Campo Visual/métodos , Tonometría Ocular , Posición Prona , Trastornos de la Visión/fisiopatología , Trastornos de la Visión/diagnósticoRESUMEN
INTRODUCTION: Our study was conducted to determine factors associated with the effectiveness of a ß-blocker eye drop add-on in altering pulse rate (PR) in glaucoma patients. METHODS: This retrospective study examined 236 eyes of 138 patients who received a ß-blocker eye drop add-on during follow-up. Patients were included if at least one PR measurement was available both before and after the add-on was started. We collected data on ophthalmic parameters: longitudinal PR; longitudinal choroidal blood flow, represented by laser speckle flowgraphy-measured mean blur rate (MBR); and diacron-reactive oxygen metabolites (d-ROMs). We used a multivariable linear mixed-effects model to investigate the effectiveness of the ß-blocker eye drop add-on in altering PR and examined factors contributing to a larger PR alteration after the add-on was started by analyzing the effect on PR of the interaction term between the add-on and clinical factors. We used the k-means method to classify the patients. RESULTS: The ß-blocker eye drop add-on reduced PR (- 7.61 bpm, P < 0.001). Female gender, higher PR when the add-on was started, lower central corneal thickness, and a higher d-ROM level were associated with greater reduction in PR (P < 0.05). In a cluster of patients with these clinical features, choroidal MBR increased by + 3.42% when we adjusted for change over time; MD slope, which represents the speed of glaucoma progression, improved by + 0.64 dB/year (P < 0.05). CONCLUSIONS: We identified a glaucoma subgroup in which PR decreased, choroidal blood flow increased, and glaucoma progression slowed after a ß-blocker eye drop add-on was started.
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Glaucoma , Presión Intraocular , Humanos , Femenino , Estudios Retrospectivos , Frecuencia Cardíaca , Estudios Longitudinales , Soluciones Oftálmicas/uso terapéutico , Glaucoma/tratamiento farmacológico , Antagonistas Adrenérgicos beta/uso terapéuticoRESUMEN
PURPOSE: To investigate the relationship between the dynamics of intraocular pressure (IOP) during dark-room prone testing (DRPT) and IOP over a relatively long-term follow-up period. METHODS: This retrospective study enrolled 84 eyes of 51 primary open-angle glaucoma patients who underwent DRPT for whom at least three IOP measurements made using Goldmann applanation tonometry were available over a maximum follow-up period of two years. We excluded eyes with a history of intraocular surgery or laser treatment and those with changes in topical anti-glaucoma medication during the follow-up period. In DRPT, IOP was measured in the sitting position, and after 60 min in the prone position in a dark room, IOP was measured again. In this study, IOP fluctuation refers to the standard deviation (SD) of IOP, and IOP max indicates the maximum value of IOP during the follow-up. The relationship between these parameters was analyzed with a linear mixed-effects model, adjusting for clinical parameters including age, gender, and axial length. RESULTS: IOP increased after DRPT with a mean of 6.13 ± 3.55 mmHg. IOP max was significantly associated with IOP after DRPT (ß = 0.38; p < 0.001). IOP fluctuation was significantly associated with IOP change in DRPT (ß = 0.29; p = 0.007). CONCLUSION: Our findings suggest that short-term and relatively long-term IOP dynamics are associated. Long-term IOP dynamics can be predicted by DRPT to some extent.
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Glaucoma de Ángulo Abierto , Glaucoma , Humanos , Presión Intraocular , Estudios de Seguimiento , Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma de Ángulo Abierto/cirugía , Estudios RetrospectivosRESUMEN
Glaucoma is a leading cause of blindness worldwide in older people. Profiling the aqueous humor, including the metabolites it contains, is useful to understand physiological and pathological conditions in the eye. In the current study, we used mass spectrometry (MS) to characterize the aqueous humor metabolomic profile and biological features of patients with glaucoma. Aqueous humor samples were collected during trabeculectomy surgery or cataract surgery and analyzed with global metabolomics. We included 40 patients with glaucoma (32 with POAG, 8 with NTG) and 37 control subjects in a discovery study. VIP analysis revealed five metabolites that were elevated and three metabolites that were reduced in the glaucoma patients. The identified metabolomic profile had an area under the receiver operating characteristic curve of 0.953. Among eight selected metabolites, the glutathione level was significantly decreased in association with visual field defects. Moreover, in a validation study to confirm the reproducibility of our findings, the glutathione level was reduced in NTG and POAG patients compared with a cataract control group. Our findings demonstrate that aqueous humor profiling can help to diagnose glaucoma and that various aqueous humor metabolites are correlated with clinical parameters in glaucoma patients. In addition, glutathione is clearly reduced in the aqueous humor of glaucoma patients with both IOP-dependent and IOP-independent disease subtypes. These findings indicate that antioxidant agents in the aqueous humor reflect glaucomatous optic nerve damage and that excessive oxidative stress may be involved in the pathogenesis of glaucoma.
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We aimed to investigate the impact of glutathione trisulfide (GSSSG) on lipopolysaccharide (LPS)-induced inflammation in retinal glia. Inflammatory responses in mouse-derived glial cells and Wistar rat retinas were stimulated with administration of LPS. Cell survival and proinflammatory cytokine production were examined using the Calcein-AM assay, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Retinal microglia were visualized with immunohistochemistry for Iba1. Administration of LPS (10 µg/mL) or GSSSG (less than 100 µM) did not affect survival of cultured primary Müller cells and established microglial cells (BV-2). RT-qPCR and ELISA indicated that GSSSG inhibited LPS-induced gene upregulation and protein secretion of proinflammatory cytokines in these glial cells and rat retinas. GSSSG inhibited LPS-induced activation of TGF-ß-activated kinase 1 (TAK1), which is an upstream kinase of NF-κB, in BV-2 cells. Finally, in vivo experiments indicated that intravitreal administration of GSSSG but not its relative glutathione disulfide (GSSG) inhibited LPS (500 ng)-induced accumulation of Iba1-immunopositive microglia in rat retinas. Taken together, GSSSG has the potential to prevent pathogenesis of inflammation-associated ocular diseases by inhibiting proinflammatory cytokine expression in retinal glial cells.
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Inflamación , Lipopolisacáridos , Ratones , Ratas , Animales , Lipopolisacáridos/metabolismo , Ratas Wistar , Inflamación/patología , Neuroglía/metabolismo , Citocinas/metabolismo , FN-kappa B/metabolismo , Microglía/metabolismoRESUMEN
Purpose: This study investigated the effect of dipeptidyl peptidase-4 inhibitors (DPP-4is) on fibrosis after glaucoma filtering surgery with clinical data and an in vitro model that used transforming growth factor-ß (TGF-ß) to induce human Tenon's fibroblast (HTF) fibrosis. Methods: The medical records of 41 eyes of 35 patients with diabetes with neovascular glaucoma (NVG) who received initial trabeculectomy were retrospectively reviewed. The surgical success rate was compared between cases that received (n = 23) and did not receive (n = 18) DPP-4i treatment for diabetes. The antifibrotic effects of linagliptin (a DPP-4i) were evaluated with quantitative real-time PCR for fibrosis markers (α-smooth muscle actin, collagen Iα, and fibronectin), a scratch assay, and a collagen gel contraction assay of primary cultured HTFs treated with TGF-ß1 and linagliptin. Western blotting analysis was performed to evaluate the levels of phosphorylated Smad2 and Smad3 in the presence of linagliptin. Results: The Kaplan-Meier curve for bleb survival was higher in patients who received DPP-4is (P = 0.017, log-rank test). The in vitro experiments demonstrated that treatment with linagliptin attenuated the elevated levels of fibrosis markers induced by TGF-ß1 in HTFs. Linagliptin treatment also prevented the migration and gel contraction of HTFs. Linagliptin inhibited the phosphorylation of Smad2 and Smad3, which is the canonical pathway of TGF-ß signaling. Conclusions: The current study indicates the potential effect of DPP-4is for maintaining bleb function after glaucoma filtering surgery in patients with diabetes with NVG. Our results demonstrate that linagliptin attenuates fibrotic change in HTFs by inhibiting TGF-ß/Smad signaling.
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Inhibidores de la Dipeptidil-Peptidasa IV , Glaucoma , Trabeculectomía , Humanos , Factor de Crecimiento Transformador beta1/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/metabolismo , Linagliptina/farmacología , Linagliptina/uso terapéutico , Linagliptina/metabolismo , Estudios Retrospectivos , Glaucoma/tratamiento farmacológico , Glaucoma/cirugía , Glaucoma/metabolismo , Fibrosis , Fibroblastos/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Transducción de Señal , Colágeno/metabolismo , Células CultivadasRESUMEN
Purpose: To investigate the association between ocular/systemic factors and visual acuity decline in glaucoma patients with loss of ganglion cell complex thickness (GCCT). Methods: In 515 eyes of 515 patients with open-angle glaucoma (mean age, 62.6 ± 12.8 years; mean deviation, -10.95 ± 9.07 dB), we used swept-source optical coherence tomography to measure macular GCCT in sectors classified as corresponding to circumpapillary retinal nerve fiber layer clock-hour sectors from 7 o'clock (inferotemporal) to 11 o'clock (superotemporal). We calculated Spearman's rank correlation coefficient between each sector and best-corrected visual acuity (BCVA), determined cutoff values for BCVA decline (<20/25), and used multivariable linear regression models to determine the correlation between BCVA and biological antioxidant potential (BAP), corneal hysteresis (CH), and temporal-tissue optic nerve head blood flow (represented by temporal mean blur rate, or MBR-T). Results: Macular GCCT corresponding to the 9 o'clock sector had the highest correlation with BCVA (Rs = -0.454; P < 0.001) and a cutoff of 76.17 µm (area under the receiver operating characteristic curve = 0.891; P < 0.001). Subjects below this cutoff (N = 173) showed significant correlations between BCVA and age, BAP, CH, and MBR-T (ß = 0.192, P = 0.033; ß = -0.186, P = 0.028; ß = -0.217, P = 0.011; and ß = -0.222, P = 0.010, respectively). Conclusions: Multiple factors are involved in BCVA decline in patients with glaucoma with decreased macular GCCT. This suggests that evaluating BCVA may require assessing multiple factors. Translational Relevance: Multiple factors contribute to BCVA decline.
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Glaucoma de Ángulo Abierto , Glaucoma , Humanos , Persona de Mediana Edad , Anciano , Glaucoma de Ángulo Abierto/complicaciones , Células Ganglionares de la Retina , Fibras Nerviosas , Glaucoma/diagnóstico , Agudeza VisualRESUMEN
PRCIS: The study suggests that a low level of systemic BDNF may contribute to the pathogenesis of glaucoma in an IOP-independent manner. AIMS: To evaluate differences in systemic brain-derived neurotrophic factor (BDNF) levels between primary open angle glaucoma (POAG) patients and normal tension glaucoma (NTG) patients. METHODS: This study collected blood samples from 260 NTG patients, 220 age-matched POAG patients, and 120 age-matched cataract patients (as controls). BDNF levels were measured with an antibody-conjugated bead assay system (Luminex). RESULTS: We found that plasma BDNF levels in the NTG group were significantly lower than in the POAG and cataract control groups. There was no significant difference between the POAG and cataract groups. CONCLUSION: This result suggests that a low level of systemic BDNF may contribute to the pathogenesis of glaucoma in an IOP-independent manner.
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Glaucoma de Ángulo Abierto , Glaucoma de Baja Tensión , Humanos , Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma de Baja Tensión/diagnóstico , Factor Neurotrófico Derivado del Encéfalo , Presión IntraocularRESUMEN
PURPOSE: We assess long-term surgical outcomes after an initial trabeculectomy for cytomegalovirus-associated anterior uveitis with secondary glaucoma (CMV-SG). METHODS: We retrospectively reviewed the medical records of 16 eyes of 15 patients with CMV-SG and 157 eyes of 157 patients with primary open-angle glaucoma. The average follow-up period was approximately 3 years. Surgical success was defined as intraocular pressure (IOP) below 18 mmHg and at least 20% lower than baseline. RESULTS: Kaplan-Meier survival analysis revealed that bleb survival rates were not significantly different in the CMV-SG and POAG groups (P = 0.75). Bullous keratopathy occurred in 2 of 16 eyes with CMV-SG postoperatively but did not occur in the POAG group. The corneal endothelial cell density decreased by 34.2 ± 22.7% in the CMV-SG group during an average follow-up period of 2.7 ± 2.0 years. CONCLUSION: Trabeculectomy effectively controlled IOP in CMV-SG, but attention must be paid to corneal endothelial cell loss.
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PURPOSE: To investigate the association of systemic oxidative stress markers and optic nerve head (ONH) blood flow in normal-tension glaucoma (NTG) patients, as well as sex differences in this association. METHODS: This was a cross-sectional study of 235 eyes with NTG of 134 patients (56 male, 78 female; mean age, 60.9±14.1 years). Laser speckle flowgraphy (LSFG) was used to measure ONH blood flow (mean blur rate in the tissue area of the ONH; MBR-T) and LSFG pulse-waveform parameters, including flow acceleration index in the tissue area of the ONH (FAI-T). Oxidative stress markers, diacron-reactive oxygen metabolites (d-ROMs), and biological antioxidant potential (BAP) were measured with a free radical elective evaluator. Spearman's rank correlation test and a multivariate linear mixed-effect model were used to investigate factors associated with ONH blood flow. RESULTS: MBR-T was significantly correlated with age (rs = -0.28, p < 0.001), mean arterial pressure (rs = -0.20, p = 0.002), intraocular pressure (rs = 0.24, p < 0.001), peripapillary retinal nerve fiber layer thickness (rs = 0.62, p < 0.001), and disc area (rs = -0.26, p < 0.001), but not with serum d-ROM level. Separate analyses of the subjects divided by sex showed that BAP was positively correlated to MBR-T (rs = 0.21, p = 0.036) and FAI-T (rs = 0.36, p < 0.001) only in male subjects. Similarly, BAP was significantly associated with MBR-T (ß = 0.25, p = 0.026) and FAI-T (ß = 0.37, p < 0.001) in male subjects in a multivariate linear mixed-effect model. CONCLUSION: A lower serum antioxidant level, as indicated by BAP, was associated with reduced ONH blood flow only in male NTG patients. Our findings suggest that there are sex differences in the involvement of oxidative stress in the pathogenesis of reduced ocular blood flow in NTG.
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Glaucoma de Baja Tensión , Disco Óptico , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Disco Óptico/irrigación sanguínea , Antioxidantes , Estudios Transversales , Caracteres Sexuales , Flujo Sanguíneo Regional/fisiología , Presión Intraocular , Estrés Oxidativo , Flujometría por Láser-Doppler , Velocidad del Flujo Sanguíneo/fisiologíaRESUMEN
Glaucoma is one of the most common causes of blindness worldwide. It is thought to be a multifactorial disease with underlying mechanisms that include mitochondrial dysfunction and oxidative stress. Here, we used NF-E2 related factor 2 (Nrf2) knockout (KO) mice, which are vulnerable to oxidative stress, to examine a neuroprotective effect against oxidative stress due to rotenone, a mitochondrial complex I inhibitor. Wild-type (WT) and Nrf2 KO mice received an oral solution of rotenone for 30 days. We then extracted the retinas and performed immunohistochemistry and quantitative RT-PCR. We also prepared a primary Müller cell culture of samples from each mouse, added 30 µM rotenone, and then measured cell viability, cytotoxicity and CellRox absorbance. We also examined gene expression. We found a significant increase in the number of 8-OHdG-positive retinal ganglion cells (RGCs) after rotenone administration in both the WT and Nrf2 KO mice. There was no difference in the number of RNA-binding protein with multiple splicing (RBPMS)-positive RGCs in the WT and Nrf2 KO mice, but Nrf2 KO mice that were given rotenone had significantly less retinal gene expression of RBPMS than Nrf2 KO mice given a control. Moreover, there was significantly higher mRNA gene expression of vimentin and glial fibrillary acidic protein (GFAP) in Nrf2 KO mice that received rotenone than WT mice that received rotenone. A statistical analysis of the in vitro experiment showed that cell viability was lower, cytotoxicity was higher, and oxidative stress was higher in the Müller cells of the Nrf2 KO mice than the WT mice. Finally, brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF) were significantly higher in the Müller cells of the Nrf2 KO mice than the WT mice. These findings suggest that in Nrf2 KO mice under oxidative stress caused by rotenone, temporary neurotrophic factors are secreted from the Müller cells, conferring neuroprotection in these cells.
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Factor 2 Relacionado con NF-E2 , Rotenona , Ratones , Animales , Ratones Noqueados , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Rotenona/toxicidad , Rotenona/metabolismo , Factores de Crecimiento Nervioso/metabolismo , Estrés Oxidativo , Neuroglía/metabolismo , Ratones Endogámicos C57BLRESUMEN
INTRODUCTION: Paget's disease of bone (PDB) is a skeletal disorder characterized by disorganized bone remodeling due to abnormal osteoclasts. Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) gene encodes the receptor activator of nuclear factor kappa B (RANK), which has a critical role in osteoclast function. There are five types of rare PDB and related osteolytic disorders due to TNFRSF11A tandem duplication variants so far, including familial expansile osteolysis (84dup18), expansile skeletal hyperphosphatasia (84dup15), early-onset familial PDB (77dup27), juvenile PDB (87dup15), and panostotic expansile bone disease (90dup12). MATERIALS AND METHODS: We reviewed a Japanese family with PDB, and performed whole-genome sequencing to identify a causative variant. RESULTS: This family had bone symptoms, hyperphosphatasia, hearing loss, tooth loss, and ocular manifestations such as angioid streaks or early-onset glaucoma. We identified a novel duplication variant of TNFRSF11A (72dup27). Angioid streaks were recognized in Juvenile Paget's disease due to loss-of-function variants in the gene TNFRSF11B, and thought to be specific for this disease. However, the novel recognition of angioid streaks in our family raised the possibility of occurrence even in bone disorders due to TNFRSF11A duplication variants and the association of RANKL-RANK signal pathway as the pathogenesis. Glaucoma has conversely not been reported in any case of Paget's disease. It is not certain whether glaucoma is coincidental or specific for PDB with 72dup27. CONCLUSION: Our new findings might suggest a broad spectrum of phenotypes in bone disorders with TNFRSF11A duplication variants.