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BACKGROUND/AIM: Diabetic retinopathy is a leading cause of blindness worldwide, characterized by neurovascular dysfunction. This study aimed to investigate the impact of brimonidine, a selective adrenoceptor agonist, on diabetic retinal neurodegeneration, recognizing the critical role of neurodegeneration in diabetic retinopathy. MATERIALS AND METHODS: Streptozotocin-induced diabetes was established in adult male Sprague-Dawley rats to mimic diabetic retinopathy. Rats, except non-diabetic control rats, received topical applications of 0.15% brimonidine tartrate (treatment group) or balanced salt solution (diabetic control group) twice daily following diabetes induction. Each group comprised six randomly assigned animals. Retinal samples were analyzed using immunofluorescence staining, apoptosis assay, and western blot. RESULTS: Topical brimonidine treatment reduced apoptosis of retinal ganglion cells at 8 weeks after induction of diabetes (p<0.05). Glial activation induced by diabetes was reduced by brimonidine treatment. Immunoblot and immunofluorescence assay revealed that the decrease in phospho- protein kinase B (AKT) level resulting from diabetes was also attenuated by brimonidine (p<0.05). Furthermore, brimonidine alleviated the decrease in anti-apoptotic proteins [BCL2 apoptosis regulator (BCL2) and BCL-xl] induced by diabetes (p<0.05). Elevation of phospho-p38 mitogen-activated protein kinase (p38MAPK) and p53 in diabetic rats were reduced by brimonidine (p<0.05). Additionally, brimonidine treatment attenuated the upregulation of the pro-apoptotic molecule BCL-2 associated X in retinas of diabetic rats (p<0.05). CONCLUSION: These findings suggest that topical brimonidine treatment may protect retinal ganglion cells in experimental diabetes by modulating the AKT pathway and reducing pro-apoptotic p38MAPK levels. This presents a potential neuroprotective approach in diabetes, offering the advantage of localized treatment without the added burden of oral medication.
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Apoptose , Tartarato de Brimonidina , Diabetes Mellitus Experimental , Retinopatia Diabética , Fármacos Neuroprotetores , Células Ganglionares da Retina , Animais , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/patologia , Tartarato de Brimonidina/farmacologia , Tartarato de Brimonidina/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/administração & dosagem , Ratos , Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Masculino , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Células Ganglionares da Retina/metabolismo , Administração Tópica , Modelos Animais de Doenças , Ratos Sprague-Dawley , Proteínas Proto-Oncogênicas c-akt/metabolismo , Retina/efeitos dos fármacos , Retina/metabolismo , Retina/patologiaRESUMO
Recent emerging studies have demonstrated numerous critical roles of exosomes in cell-to-cell signaling. We investigated exosomes in the aqueous humor of glaucoma patients and controls and compared their characteristics with other biomarkers such as cytokines. Glaucoma patients exhibited higher exosome particle counts and smaller sizes compared to controls. Higher exosome density was correlated with more severe visual field loss. Conversely, concentrations of aqueous humor cytokines, particularly PD-L1, were primarily associated with intraocular pressure, and none of the cytokines showed a significant association with visual field damage. This may reflect the characteristics of exosomes, which are advantageous for crossing various biological barriers. Exosomes may contain more information about glaucoma functional damage occurring in the retina or optic nerve head. This highlights the potential importance of exosomes as signaling mediators distinct from other existing molecules.
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Humor Aquoso , Biomarcadores , Citocinas , Exossomos , Glaucoma , Humanos , Humor Aquoso/metabolismo , Exossomos/metabolismo , Biomarcadores/metabolismo , Glaucoma/metabolismo , Glaucoma/patologia , Citocinas/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Pressão Intraocular , Estudos de Casos e ControlesRESUMO
In the context of glaucoma, intraocular pressure (IOP) and age are recognized as the primary factors contributing to its onset and progression. However, significant reductions in IOP fail to completely halt its advancement. An emerging body of literature highlights the role of neuroinflammation in glaucoma. This study aimed to explore Bromfenac's anti-inflammatory properties in mitigating neuroinflammation associated with glaucoma using an ischemia-reperfusion (IR) glaucoma model. Bromfenac's impact on microglia and astrocytes under pressure was assessed via Western blotting and an enzyme-linked immunosorbent assay. Immunohistochemical staining was used to evaluate glial activation and changes in inflammatory marker expression in the IR model. Bromfenac led to the downregulation of inflammatory markers, which were elevated in the conditions of elevated pressure, and necroptosis markers were downregulated in astrocytes. In the IR model, elevated levels of GFAP and Iba-1 indicated glial activation. Following Bromfenac administration, levels of iNOS, COX-2, and PGE2-R were reduced, suggesting a decrease in neuroinflammation. Furthermore, Bromfenac administration in the IR model resulted in the improved survival of retinal ganglion cells (RGCs) and preservation of retinal function, as demonstrated by immunohistochemical staining and electroretinography. In summary, Bromfenac proved effective in diminishing neuroinflammation and resulted in enhanced RGC survival.
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Astrócitos , Benzofenonas , Bromobenzenos , Modelos Animais de Doenças , Glaucoma , Traumatismo por Reperfusão , Bromobenzenos/farmacologia , Bromobenzenos/uso terapêutico , Animais , Benzofenonas/farmacologia , Benzofenonas/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/complicações , Glaucoma/tratamento farmacológico , Glaucoma/patologia , Glaucoma/complicações , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Astrócitos/patologia , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/patologia , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Células Ganglionares da Retina/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Masculino , Pressão Intraocular/efeitos dos fármacos , RatosRESUMO
BACKGROUD: The aim of this study was to investigate the associations between fluctuation in blood pressure (BP), ocular perfusion pressure (OPP) and visual field (VF) progression in normal-tension glaucoma (NTG). METHODS: This prospective, longitudinal study included 44 patients with NTG. Only newly diagnosed NTG patients who had not been treated with a glaucoma medication were included. Patients were examined every year for 7 years. Intraocular pressure (IOP), heart rate (HR), systolic BP (SBP), diastolic BP (DBP), ocular perfusion pressure (OPP), and diastolic ocular perfusion pressure (DOPP) were measured at the same time. Ophthalmic examinations, including perimetry, were performed also. Initial VF were compared with follow-up data after 7 years. RESULTS: After 7 years of follow-up, 9 of the 44 patients showed VF progression. The standard deviation (SD) of SBP and OPP were significantly associated with VF progression (P = 0.007, < 0.001, respectively). Multiple regression analysis showed that VF progression was significantly associated with SD of OPP (odds ratio, OR = 2.012, 95% CI = 1.016-3.985; P = 0.045). CONCLUSIONS: Fluctuation in OPP was associated with VF progression in patients with NTG.
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Pressão Sanguínea , Progressão da Doença , Pressão Intraocular , Glaucoma de Baixa Tensão , Campos Visuais , Humanos , Glaucoma de Baixa Tensão/fisiopatologia , Campos Visuais/fisiologia , Masculino , Feminino , Pressão Intraocular/fisiologia , Estudos Prospectivos , Pessoa de Meia-Idade , Pressão Sanguínea/fisiologia , Seguimentos , Idoso , Testes de Campo Visual , AdultoRESUMO
Increased intraocular pressure (IOP) is the most important risk factor for glaucoma. The role of IOP fluctuation, independently from elevated IOP, has not yet been confirmed in glaucoma. We investigated the effects of IOP fluctuation itself on retinal neurodegeneration. Male rats were treated with IOP-lowering eyedrops (brinzolamide and latanoprost) on Mondays and Thursdays (in the irregular instillation group) or daily (in the regular instillation group), and saline was administered daily in the normal control group for 8 weeks. The IOP standard deviation was higher in the irregular instillation group than the regular instillation group or the control group. The degree of oxidative stress, which was analyzed by labeling superoxide, oxidative DNA damage, and nitrotyrosine, was increased in the irregular instillation group. Macroglial activation, expressed by glial fibrillary acidic protein in the optic nerve head and retina, was observed with the irregular instillation of IOP-lowering eyedrops. Microglial activation, as indicated by Iba-1, and the expression of TNF-α did not show a significant difference between the irregular instillation and control groups. Expression of cleaved caspase-3 was upregulated and the number of retinal ganglion cells (RGCs) was decreased in the irregular instillation group. Our findings indicate that IOP fluctuations could be induced by irregular instillation of IOP-lowering eyedrops and this could lead to the degeneration of RGCs, probably through increased oxidative stress and macrogliosis.
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Glaucoma , Pressão Intraocular , Masculino , Animais , Ratos , Retina , Glaucoma/tratamento farmacológico , Células Ganglionares da Retina , Soluções OftálmicasRESUMO
Background: Thickening of the inner nuclear layer (INL) or microcystic macular changes has been reported to be implicated in glaucoma patients, but their potential impact on disease progression remains unclear. We investigated the relationship between baseline microcystic macular edema in the INL or INL thickness and subsequent visual field (VF) progression in glaucoma patients. Methods: This retrospective observational study included primary open-angle glaucoma with follow-up exceeding 3 years. We identified macular cystic changes through Spectralis optical coherence tomography and measured the INL thickness using automated segmentation. Glaucoma progression was determined using the Guided Progression Analysis program of the Humphrey filed analyzer, calculating the mean deviation (MD) changes (dB/year). Results: Microcystic macular changes were observed in 12 (7.5%) of 162 patients. Patients with microcystic macular change had thicker INL thickness than those without it (p = 0.010). Progressors had a higher probability of having microcystic macular changes and a thicker average INL thickness than nonprogressors (p = 0.003, p = 0.019). Thicker INL thickness was associated with faster VF progression based on MD slope (dB/year) in the multivariate regression analysis (p = 0.045). Additionally, greater intraocular pressure (IOP) fluctuation was found to be associated with both a thicker INL and the presence of microcystic changes in the multivariate regression analysis (p = 0.003, 0.028). Conclusions: Increased macular INL thickness indicative of INL changes was linked to subsequent VF progression in glaucoma patients. These findings suggest that retinal inner nuclear change could serve as an indicator of progressive glaucoma.
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Purpose: The purpose of this study was to investigate the clinical significance of recurrent disc hemorrhage (DH) and choroidal microvasculature dropout (MvD). Methods: A retrospective cohort study was conducted of 181 eyes with open-angle glaucoma. The clinical characteristics of patients with nonrecurrent and recurrent DH with and without MvD were investigated. Results: Fifty-eight patients (32.0%) had a single, nonrecurrent DH, and 63 (34.8%) had more than one DH. Sixty eyes (33.1%) with no history of DH were presented as a control group. MvD was more frequent in the recurrent DH group (44.4%) than in the nonrecurrent DH group (27.6%, P = 0.041). The recurrent DH with MvD group experienced more frequent central visual field (VF) progression (71.4%) than the recurrent DH without MvD group (17.1 %, P < 0.001). The recurrent DH without MvD group had a higher frequency of DH recurrence at different locations (42.9%) and more vascular symptoms (37.1%) than the recurrent DH with MvD group (14.3% and 7.1%, P = 0.013 and P = 0.005, respectively). Presence of DH, presence of MvD, vascular symptoms, and DH recurrence at different locations were the factors associated with central VF progression in multivariate analysis. Conclusions: DH occurrence and the presence of MvDs constitute critical parameters associated with central VF progression. In the presence of MvD, recurrent DH was more likely to recur at the same location as the MvD, whereas recurrent DH without MvD was related to vascular symptoms and recurred at other locations. When eyes present with recurrent DH and MvD, closer follow-up and more aggressive treatment are required to prevent the progression of central VF.
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Glaucoma de Ângulo Aberto , Glaucoma , Humanos , Tomografia de Coerência Óptica , Glaucoma de Ângulo Aberto/diagnóstico , Relevância Clínica , Estudos Retrospectivos , Microvasos , Hemorragia , Corioide , AngiografiaRESUMO
PURPOSE: To compare the differences between eyes with pseudoexfoliative glaucoma (PXG) when they are divided into two groups (hypertensive PXG and normotensive PXG) according to the intraocular pressure (IOP). METHODS: This is a retrospective study. Data from 86 hypertensive PXG eyes and 80 normotensive PXG eyes were included. Hypertensive PXG was defined as PXG with IOP ≥ 22 mmHg, and normotensive PXG was defined as with IOP ≤ 21 mmHg). Central corneal thickness (CCT) was measured by ultrasound pachymetry. Lamina cribrosa thickness (LT) was evaluated using swept-source optical coherence tomography. RESULTS: No significant differences were observed between hypertensive and normotensive PXG in terms of age, gender, axial length, hypertension, or diabetes. Normotensive PXG eyes had thinner CCT than hypertensive PXG eyes (p = 0.02). To compare LT, a sub-analysis was performed after matching age, VF MD and retinal nerve fiber layer thickness. The normotensive PXG group (n = 32) demonstrated significantly thinner LT compared with the hypertensive PXG group (n = 32) at similar ages and levels of glaucoma severity (p < 0.001). CONCLUSIONS: Eyes with normotensive PXG demonstrated thinner CCT and LT compared with those with hypertensive PXG, suggesting structural vulnerability to glaucoma.
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Background: A relationship between glaucoma and epiretinal membrane (ERM) has been suggested previously. We investigated the association between intraocular pressure (IOP) fluctuation and idiopathic ERM in patients with glaucoma or glaucoma suspect. Methods: Among patients with glaucoma or glaucoma suspect, data from 43 patients with ERM and 41 patients without ERM were reviewed and analyzed in this retrospective study. The long-term fluctuation of IOP was defined based on the standard deviation of IOP across all visits. Results: Patients with ERM were older and had a higher SD of IOP and a higher proportion of having a history of cataract surgery and greater macular thickness (p = 0.018, 0.049, 0.013, and <0.001, respectively). In multiple logistic regression analysis, the high-IOP-fluctuation group was associated with the presence of ERM (p = 0.047). Among patients with ERM, eyes with stage-3 or -4 ERM had worse visual field defects based on mean deviation than those with stage-1 or -2 ERM (p = 0.025). Conclusions: Long-term IOP fluctuation was associated with idiopathic ERM in patients with glaucoma or glaucoma suspect. Idiopathic ERM could serve as a biomarker for long-term IOP fluctuation in glaucoma patients, particularly in clinics where measuring long-term IOP fluctuation during the first visit is not feasible due to its time-consuming nature.
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PURPOSE: To observe the development of glaucoma in myopic eyes with and without myopic optic neuropathy (MON) and analyze associated factors to the development of typical glaucomatous damage. DESIGN: A prospective, observational, cohort study. METHODS: A total of 233 myopic eyes with no definite evidence of glaucomatous damage were included. Myopic patients without any retinal nerve fiber layer (RNFL) or visual field (VF) abnormalities were classified as myopic eyes without MON. Myopic patients with decreased RNFL at the superonasal (SN) or nasal area, and with corresponding VF defects either in the temporal or inferotemporal (IT) region were classified as myopic eyes with MON. Myopic eyes that developed glaucoma were defined by the presence of glaucomatous VF in the SN region including defects in Bjerrum area, or a new localized RNFL defect in the IT region. Disc morphological features and optic nerve head (ONH) parameters of two groups were compared. RESULTS: Myopic eyes with MON had a thinner average peripapillary RNFL thickness (P < 0.001), worse MD of the VF (P = 0.031), a higher percentage of IT VF defects (P < 0.001), smaller torsion degree (P = 0.047), and greater LCD (P = 0.022). Myopic eyes with MON who developed glaucoma had a thinner average peripapillary RNFL thickness (P = 0.009), greater PPA area (P = 0.049), greater LCD (P < 0.001), and thinner LCT (P < 0.001). Thinner baseline temporal RNFL thickness (HR, 0.956; 95% CI, 0.928-0.986; P = 0.004), greater baseline LCD (HR, 1.003; 95% CI, 1.000-1.005; P = 0.022), and greater PPA area (HR, 1.000; 95% CI, 1.000-1.003; P = 0.050) were significantly associated factors with glaucoma development. CONCLUSIONS: Myopic eyes with MON have a greater risk to develop glaucoma compared to myopic eyes without MON. Structural weakness due to myopia, especially at the temporal side of the ONH and the peripapillary sclera, increases the risk of glaucoma in myopic eyes with MON.
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Glaucoma , Miopia , Doenças do Nervo Óptico , Humanos , Estudos de Coortes , Estudos Prospectivos , Tomografia de Coerência Óptica , Glaucoma/complicações , Glaucoma/diagnóstico , Doenças do Nervo Óptico/diagnóstico , Doenças do Nervo Óptico/etiologia , Miopia/complicações , Miopia/diagnóstico , Transtornos da Visão , Pressão IntraocularRESUMO
The surface area of encapsulation around the Ahmed glaucoma valve (AGV) endplate is a critical factor in the surgical outcome as it is associated with the degree of IOP reduction. We investigated the surgical outcome of AGV implantation with an additional pericardium graft inserted adjacent to the endplate, with the intent of expanding the surface area of encapsulation. We enrolled 92 patients (92 eyes) who underwent AGV implantation. Of them, 50 patients underwent conventional surgery (termed the without-expansion group), and 42 received an additional an 8 × 6 mm pericardium graft inserted adjacent to the AGV endplate at the sub-Tenon's space (with-expansion). The hypertensive phase was classified as mild (>21 mmHg), moderate (>25 mmHg), and severe (>30 mmHg). Six months post-surgery, the with-expansion group exhibited a lower IOP (14.90 ± 4.27 mmHg) and lower peak IOP (22.29 ± 4.95 mmHg) than the without-expansion group (17.56 ± 4.88 mmHg and 25.06 ± 6.18 mmHg, p = 0.008 and p = 0.021, respectively). The with-expansion group exhibited a relatively low rate of moderate (16.7%) and severe (4.8%) hypertensive phases compared to the without-expansion group (40.0% and 20.0%, with p = 0.014 and p = 0.031, respectively). The additional pericardium graft was associated with a reduced occurrence of moderate hypertensive phase in both univariate and multivariate analysis logistic regression analyses (p = 0.017 and p = 0.038, respectively). Endplate surface area expansion using an additional pericardium graft reduced the occurrence of moderate and severe hypertensive phases, and lower postoperative 6-month IOP could be achieved.
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To explore various parameters that can evaluate the central visual impairment in patients with early-stage glaucoma, we included patients into a study with central visual impairments with an MD value greater than -6.0 dB on the 24-2 VF test. A possible association between structural parameters acquired by OCT and functional parameters of VF and PERG was determined. A total of 70 eyes of patients with suspected glaucoma or NTG underwent VF, OCT, and PERG examinations. The patients were classified into two groups according to the MD of the 24-2 VF test. We used Pearson correlation analysis to evaluate the relationships between GCIPL thickness/RNFL thickness and visual functional parameters, such as PERG and perimetry. Linear regression analyses were conducted to evaluate the significant factors affecting the PSD of VF 10-2. In the low MD group, the P50 amplitude presented significant correlations (r = 0.346, p = 0.048) with GCIPL thickness. In the correlation analysis of the high MD group, it was found that only the PSD of 10-2 uniquely presented borderline significant correlations with GCIPL thickness (r = -0.327, p = 0.055), and no other functional parameter showed significant correlation. Univariate and multivariate analyses revealed that GCIPL thickness was significantly associated with a PSD of 10-2 VF (p < 0.001 and 0.013, respectively). Among various parameters, the P50 amplitude and 10-2 PSD demonstrated statistically borderline significant structure-function relationships with GCIPL thickness in early-stage glaucoma.
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Purpose: To investigate whether the trajectories of saccadic eye movements (SEMs) significantly differ between glaucoma patients and controls. Methods: SEMs were recorded by video-based infrared oculography in 53 patients with glaucoma and 41 age-matched controls. Participants were asked to bilaterally view 24°-horizontal, 14°-vertical, and 20°-diagonal eccentric Goldmann III-sized stimuli. SEMs were evaluated with respect to the saccadic reaction time (SRT), the mean velocity, amplitude, and two novel measures: departure angle (DA) and arrival angle (AA). These parameters were compared between the groups and the associations of SEM parameters with glaucoma parameters and integrated visual field defects were investigated. Results: Glaucoma patients exhibited increased mean SRT, DA, and AA values compared with controls for 14°-vertical visual targets (P = 0.05, P < 0.01, and P < 0.01, respectively). The SRT, DA, and AA were significantly associated with the mean and pattern standard deviations of perimetry and with the mean RNFL thickness by OCT (all P < 0.001). Glaucoma was associated with the AA (P = 0.05) and both the SRT (P = 0.01) and DA (P = 0.04) were associated with integrated visual field defects. Conclusions: The saccadic trajectories of glaucoma patients depart in an erroneous path and compensate the disparity by deviating the trajectory at arrival. Translational Relevance: The initial deviation that we observed (despite continuous exposure to the stimulus) suggests the disoriented spatial perception of glaucoma patients which may be relevant to difficulties encountered daily.
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Glaucoma , Movimentos Sacádicos , Humanos , Campos Visuais , Glaucoma/diagnóstico , Testes de Campo Visual/métodos , Transtornos da Visão , BiometriaRESUMO
Superficial and deep macular vessel density (VD) is decreased in eyes with glaucoma. Superficial VD comprises both the retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer (GC/IPL), and various terms have been used previously to describe the layers of macular VD. In our study, we readjusted the macular segmentation. We obtained RNFL and GC/IPL VDs separately to evaluate VD changes of axon versus soma/dendrite of the retinal ganglion cells (RGCs) in detail. We included 66 eyes of normal tension glaucoma patients with inferior localized RNFL defects solely impacting the inferior hemiretina. Macular VD was measured as RNFL VD and GC/IPL VD. VD ratio was calculated by dividing the VD from the affected hemiretina by the VD from the unaffected hemiretina. RNFL VD ratio was related to RNFL and GC/IPL thicknesses (p = 0.005, p = 0.001), whereas GC/IPL VD ratio was not (p = 0.596, p = 0.783). A lower GC/IPL VD ratio was associated with lower RNFL VD (p = 0.017) and systemic hypertension (p = 0.03) in multivariate analysis. Patients with a reduced GC/IPL VD ratio were more prone to poor visual field defects (p = 0.022) and paracentral scotoma (p = 0.046) and more likely to be on treatment for systemic hypertension (p = 0.024). Therefore, glaucoma patients on systemic hypertension treatment and reduced GC/IPL VD require cautious management.
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PURPOSE: To identify factors associated with the development of epiretinal membranes (ERM) in glaucoma patients. DESIGN: Multicenter, propensity-score matched, case-control study. METHODS: One hundred ninety-two eyes of 192 patients with glaucoma from the Catholic Medical Center Glaucoma Suspect Cohort Study were analyzed. We identified 64 eyes who developed ERM from the cohort, and 128 eyes without ERM were selected by propensity score matching (1:2) according to baseline age and mean deviation (MD) of the visual field (VF). Demographic, systemic, and ocular characteristics were determined at baseline. Intraocular pressure (IOP) was measured, including baseline, mean IOP, and IOP fluctuation. Early-stage ERM, defined as translucent membrane with no underlying retinal distortion, was detected by fundus photography and optical coherence tomography. Central VF progression was considered when new VF defets developed in one either or both hemifields or when there was an increase of 3 or more abnormal points within 12 points of central 10° fixation. Autonomic nervous system status was evaluated by heart rate variability. RESULTS: Patients who developed ERM were more frequently receiving medication for systemic hypertension and had higher systolic blood pressure, greater IOP fluctuation, more frequent disc hemorrhage (DH), worse VF MD, and a higher rate of central VF progression than patients without ERM. Additionally, patients with early glaucoma who developed ERM had higher rate of autonomic imbalance while patients with moderate-to-advanced glaucoma who developed ERM had greater baseline and peak IOP and worse MD of the last follow-up VF (MD < 6.0 dB). Older age (P = .048), medication for systemic hypertension (P < .001), IOP fluctuation (P < .001), presence of DH (P < .001), and worse last MD of VF (P = .033) were significantly associated with ERM in Cox proportional hazard analysis. CONCLUSIONS: Early stage of ERMs in glaucomatous eyes are significantly associated with glaucoma progression, medication of systemic hypertension, presence of DH, and IOP fluctuation. These suggest that glaucoma patients who develop early stage of ERMs should be carefully monitored in terms of IOP fluctuation, vascular factors, and glaucoma progression.
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Membrana Epirretiniana , Glaucoma , Hipertensão , Humanos , Pressão Intraocular , Estudos de Casos e Controles , Membrana Epirretiniana/diagnóstico , Membrana Epirretiniana/etiologia , Estudos de Coortes , Transtornos da Visão , Progressão da Doença , Testes de Campo VisualRESUMO
PURPOSE: To investigate associated factors including structural parameters of myopia and vessel density (VD) using optical coherence tomography angiography (OCT-A) to visual acuity (VA) and central visual function in glaucoma patients with myopia. DESIGN: Retrospective cross-sectional study. METHODS: Sixty-five eyes of 60 glaucoma patients with myopia and without media opacity and retinal lesions were included. Both Swedish interactive thresholding algorithm (SITA) 24-2 and 10-2 visual field (VF) testing were performed. Superficial and deep VD in the peripapillary and macular regions were evaluated using OCT-A; retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thicknesses were measured. ß-zone peripapillary atrophy (PPA) area, disc torsion, disc-fovea distance, and peripapillary choroidal thickness were measured. Decreased VA was defined as best-corrected VA <20/25. RESULTS: The worse mean deviation of SITA 24-2, thinner GCIPL thickness, and lower deep peripapillary VD were associated with the presence of central VF damage in glaucoma patients with myopia. Thinner GCIPL thickness, lower deep peripapillary VD, and longer disc-fovea distance were associated with decreased VA in logistic regression analysis. Thinner GCIPL thickness, lower deep peripapillary VD, and larger ß-zone PPA area were associated with lower VA in linear regression analysis. Deep peripapillary VD showed a positive correlation with GCIPL thickness, whereas there was no relationship between deep peripapillary VD and RNFL thickness. CONCLUSION: Decreased VA in glaucoma patients with myopia was associated with lower deep peripapillary VD and papillomacular bundle damage. Lower deep peripapillary VD was independently associated with decreased VA along with thinner GCIPL thickness. Therefore, it could be stated that decreased VA in glaucoma patients is related to the damage location and the status of blood flow in the optic nerve head.
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Glaucoma , Miopia , Humanos , Estudos Retrospectivos , Estudos Transversais , Células Ganglionares da Retina/patologia , Glaucoma/complicações , Glaucoma/diagnóstico , Glaucoma/patologia , Miopia/complicações , Miopia/diagnóstico , Miopia/patologia , Acuidade Visual , Tomografia de Coerência Óptica/métodosRESUMO
We identify the angiotensin II (AngII)-associated changes in the extracellular matrix (ECM) and the biomechanical properties of the sclera after systemic hypotension. Systemic hypotension was induced by administering oral hydrochlorothiazide. AngII receptor levels and ECM components in the sclera and biomechanical properties were evaluated based on the stress-strain relationship after systemic hypotension. The effect of inhibiting the AngII receptor with losartan was determined in the systemic hypotensive animal model and the cultured scleral fibroblasts from this model. The effect of losartan on retinal ganglion cell (RGC) death was evaluated in the retina. Both AngII receptor type I (AT-1R) and type II (AT-2R) increased in the sclera after systemic hypotension. Proteins related to the activation of fibroblasts (transforming growth factor [TGF]-ß1 and TGF-ß2) indicated that transformation to myofibroblasts (α smooth muscle actin [SMA]), and the major ECM protein (collagen type I) increased in the sclera after systemic hypotension. These changes were associated with stiffening of the sclera in the biomechanical analysis. Administering losartan in the sub-Tenon tissue significantly decreased the expression of AT-1R, αSMA, TGF-ß, and collagen type I in the cultured scleral fibroblasts and the sclera of systemic hypotensive rats. The sclera became less stiff after the losartan treatment. A significant increase in the number of RGCs and decrease in glial cell activation was found in the retina after the losartan treatment. These findings suggest that AngII plays a role in scleral fibrosis after systemic hypotension and that inhibiting AngII could modulate the tissue properties of the sclera, resulting in the protection of RGCs.
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PURPOSE: To investigate the characteristics of normotensive glaucoma (NTG) in the fellow eye of patients with unilateral pseudoexfoliation syndrome (PXS). METHODS: This study is a retrospective chart review. We included 313 patients with NTG. Using the 1:1 matched propensity score, only 94 well-matched patients were selected. A total of 47 NTG patients who had PXS in their contralateral eye (PXS group) and 47 NTG patients who did not (control group) were compared. The propensity score was matched based on age, mean intraocular pressure (IOP), baseline retinal nerve fiber layer (RNFL) thickness and baseline mean deviation (MD) of visual field (VF) score. The diagnosis of NTG was based on the presence of glaucomatous optic nerve head injury with VF defect, intraocular pressure less than 22 mmHg, open angles and no pseudoexfoliation material. RESULTS: The PXS group had a higher ratio of males (34.0%) than the control group (17.0%). No significant differences were observed between the two groups in terms of CCT, axial length, untreated baseline IOP, baseline PSD of VF, systemic blood pressure and follow-up duration. The rate of RNFL thinning was significantly faster in the PXS group (-1.88 ± 2.83 µm/year) compared with the control group (-0.27 ± 5.29 µm/year) (p = 0.02). The progression rate of VF MD was slightly faster in PXS than in the control group, but there was no statistically significant difference (PXS group, -0.33 ± 0.90 dB/year; control group, -0.11 ± 0.84 dB/year; p = 0.236). CONCLUSIONS: NTG eyes with PXS showed faster RNFL thinning than did control NTG eyes.
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PURPOSE: To investigate the relationship between cytokines of the aqueous humor or Tenon capsule, the onset of a hypertensive phase, and surgical failure in patients undergoing Ahmed Glaucoma Valve (AGV) implantation DESIGN: Prospective clinical cohort study. METHODS: A total of 36 patients who underwent AGV implantation were included. Samples of aqueous humor and Tenon tissue were collected at the time of surgery. Multiple cytokines were evaluated in the samples using a bead-based multiplex cytokine assay. As for surgical outcomes, a hypertensive phase was defined as an intraocular pressure (IOP) of greater than 21 mm Hg within 3 months after surgery, whereas surgical failure was defined as an IOP greater than 21 mm Hg with maximum tolerable glaucoma medications during 2 consecutive visits. RESULTS: Patients who entered a hypertensive phase showed higher transforming growth factor-ß2 (TGF-ß2) levels in the aqueous humor (P = .012). A longer axial length and higher TGF-ß2 concentration of the aqueous humor were associated with higher maximum IOP values during 3 months after surgery per multiple regression analysis (P = .028 and P = .034). In the multiple logistic regression analysis, higher monocyte chemoattractant protein-1 (MCP-1) concentrations in the aqueous humor and higher interleukin-4 concentrations in Tenon tissue were related to surgical failure (P = .022 and P = .040). CONCLUSIONS: Greater concentrations of TGF-ß2 and MCP-1 were related to surgical outcome after glaucoma drainage device implantation. Further studies are needed to confirm that down-regulation of these cytokines could be helpful in improving surgical outcomes.
Assuntos
Implantes para Drenagem de Glaucoma , Glaucoma , Humanos , Fator de Crescimento Transformador beta2/uso terapêutico , Citocinas , Estudos Prospectivos , Estudos de Coortes , Seguimentos , Pressão Intraocular , Implantação de Prótese , Resultado do Tratamento , Estudos RetrospectivosRESUMO
We aimed to characterize and compare the occurrence of peripapillary microvasculature dropout (MvD) between glaucoma suspects and patients with glaucoma. In addition, the factors related to the development of parapapillary MvD in glaucoma suspects and patients with glaucoma were investigated. Of a total 150 eyes, 68 eyes of glaucoma suspects and 82 eyes of glaucoma patients were analyzed in this study. Univariate and multivariate logistic regression analyses were used to identify factors associated with MvD development. The classification of glaucoma patients or glaucoma suspects was not significantly associated with MvD development (beta 1.368, 95% CI, 0.718-2.608, p = 0.341). In the regression analysis of the glaucoma suspect group, greater axial length (beta 1.520, 95% CI, 1.008-2.291, p = 0.046) and baseline cup volume (beta 3.993, 95% CI, 1.292-12.345, p = 0.035) among the baseline factors and the slope of ganglion cell-inner plexiform layer (GCIPL) thickness (beta 0.027, 95% CI, 0.072-0.851, p = 0.027) and central visual field (VF) progression (beta 7.040, 95% CI, 1.781-16.306, p = 0.014) among follow-up factors were significantly associated with MvD development. In the glaucoma group, central VF progression (beta 5.985, 95% CI, 1.474-24.083, p = 0.012) and ONH depression (beta 3.765, 95% CI, 1.301-10.895, p = 0.014) among follow-up elements were observed as significant factors and the baseline factor had little relationship. MvD appears not only as a result of the progression of axonal loss of RGC in glaucoma but may also be developed due to structural changes and mechanical susceptibility of the ONH associated with baseline characteristics. Analyzing the structural susceptibility of the ONH can predict the occurrence of MvD, which can be helpful in predicting the progression of glaucoma.