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Glaucoma is one of the leading causes of irreversible blindness. Stem cell therapy has shown promise in the treatment of primary open-angle glaucoma in animal models. Stem cell-free therapy using stem cell-derived trophic factors might be in demand in patients with high-risk conditions or religious restrictions. In this chapter, we describe methods for trabecular meshwork stem cell (TMSC) cultivation, secretome harvesting, and protein isolation, as well as assays to ensure the health of TMSC post-secretome harvesting and for secretome periocular injection into mice for therapeutic purposes.
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Células-Tronco , Malha Trabecular , Malha Trabecular/metabolismo , Malha Trabecular/citologia , Animais , Camundongos , Humanos , Células-Tronco/citologia , Células-Tronco/metabolismo , Regeneração , Glaucoma/terapia , Transplante de Células-Tronco/métodos , Secretoma , Modelos Animais de Doenças , Glaucoma de Ângulo Aberto/terapia , Células Cultivadas , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Técnicas de Cultura de Células/métodosRESUMO
Purpose: To investigate the usefulness of intraocular pressure (IOP) using the ocular response analyzer to predict the occurrence of hypotony complications following trabeculectomy or bleb needling revision with mitomycin C. Methods: This study included 66 eyes of 66 patients who underwent trabeculectomy (58 eyes of 58 patients) or bleb needling (8 eyes of 8 patients) with mitomycin C. A significant predictor of hypotony complications was identified from (1) operation (trabeculectomy or bleb needling), (2) age, (3) sex, (4) disease type (primary open-angle glaucoma, primary angle closure glaucoma, or exfoliation glaucoma), (5) lens status (phakia or pseudophakia), (6) preoperative Goldmann applanation tonometry IOP, (7) preoperative central corneal thickness, (8) preoperative axial length, (9) preoperative anterior chamber depth, (10) preoperative corneal hysteresis, (11) preoperative corneal resistance factor, (12) preoperative corneal compensated IOP (IOPcc), and (13) minimum IOP (IOP value when hypotony complications occurred, otherwise the minimum IOP during 3 months from trabeculectomy or bleb needling) using multivariate logistic regression. Results: The probability of the occurrence of hypotony complications tended to increase by applying higher cutoff values to preoperative Goldmann applanation tonometry IOP and IOPcc, but not lower cutoff values to the minimum IOP. Multivariate logistic regression suggested that higher preoperative IOPcc and pseudophakia were significant predictors of the occurrence of hypotony complications (P = 0.0062 and 0.0069, respectively). Conclusions: Higher preoperative IOPcc and pseudophakia were significant predictors of the occurrence of hypotony complications. Translational Relevance: It is useful to measure IOP using the ocular response analyzer before trabeculectomy.
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Pressão Intraocular , Hipotensão Ocular , Complicações Pós-Operatórias , Tonometria Ocular , Trabeculectomia , Humanos , Feminino , Pressão Intraocular/fisiologia , Masculino , Trabeculectomia/efeitos adversos , Idoso , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Tonometria Ocular/instrumentação , Tonometria Ocular/métodos , Hipotensão Ocular/etiologia , Idoso de 80 Anos ou mais , Glaucoma/cirurgia , Glaucoma/fisiopatologia , Adulto , Estudos Retrospectivos , Glaucoma de Ângulo Aberto/cirurgiaRESUMO
BACKGROUND: Bilateral malignant glaucoma induced by a capsular tension ring associated with ring-shaped cysts of the ciliary body post-cataract surgery is rare. Herein, we present a case to highlight the possibility of capsular tension ring-induced malignant glaucoma. CASE PRESENTATION: A 59-year-old woman underwent phacoemulsification combined with capsular tension ring implantation for cataracts and zonular fibre laxity in both eyes. Upon admission, annular ciliary masses were detected in both eyes using ultrasound biomicroscopy. Two months post-surgery, the patient experienced vision deterioration, high intraocular pressure, and an axial shallowing anterior chamber in the right eye, and responded poorly to traditional anti-glaucoma medication. Ten days later, similar symptoms appeared in the left eye. Ultrasound biomicroscopy detected contact between the ciliary body and the capsular tension ring. Subsequently, malignant glaucoma was diagnosed. Anterior and posterior capsulotomies performed peripheral to intraocular lens optics using neodymium: YAG laser restored communication and alleviated the symptoms. A one-year follow-up revealed stable intraocular pressure and anterior chamber in both eyes. CONCLUSIONS: This is the first case report of bilateral malignant glaucoma after cataract surgery induced by capsular tension ring, which is associated with bilateral ring-shaped cysts of the ciliary body. Blockage between the ciliary body and capsular tension ring was confirmed using ultrasound biomicroscopy.
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Corpo Ciliar , Glaucoma , Pressão Intraocular , Facoemulsificação , Humanos , Feminino , Pessoa de Meia-Idade , Pressão Intraocular/fisiologia , Glaucoma/etiologia , Glaucoma/cirurgia , Facoemulsificação/efeitos adversos , Corpo Ciliar/diagnóstico por imagem , Microscopia Acústica , Complicações Pós-Operatórias , Implante de Lente Intraocular/efeitos adversos , Catarata/etiologia , Próteses e Implantes/efeitos adversos , Implantação de Prótese/efeitos adversosRESUMO
BACKGROUND: Glaucoma is an irreversible silent and dangerous eye condition that leads to damage of the optic nerve head. This study aimed to determine the outcome of targeted glaucoma outreaches done in the University of Ilorin Teaching Hospital over three years with a view to early detection and timely institution of management. METHODS: The study is a retrospective review of 3 targeted hospital-based glaucoma screenings, World Sight Day of 2019 (140 participants), World Glaucoma Week of 2020 (176 participants), and World Glaucoma Week of 2022 (183 participants). The criteria for diagnosing glaucoma and glaucoma suspects were taken from the national study of prevalence and types of glaucoma from the Nigerian national blindness survey and International Society for Geographical and Epidemiological Ophthalmology criteria. RESULTS: The study population had a mean age of 45.54 years (SD 16.92) with individuals within the age group of 51-60 years comprising the majority of the participants (26.4%). Most participants had normal vision or mild visual impairment in the right eye (411, 86.1%) and left eye (405, 84.9%) while blindness was recorded in the right eye of 37 (7.7%) participants and left eye of 36 (7.5%). The prevalence of glaucoma cases and suspects among study participants was 29.4% and 42.5%, respectively. There was a statistically significant relationship between the diagnosis of glaucoma and older age, family history of glaucoma and elevated intraocular pressure. CONCLUSION: This study showed that targeted screening for glaucoma is an invaluable tool for ensuring early detection of the disease.
CONTEXTE: Le glaucome est une affection oculaire silencieuse et dangereuse qui entraîne des dommages au nerf optique. Cette étude visait à déterminer les résultats des campagnes de dépistage ciblé du glaucome menées à l'Hôpital universitaire d'Ilorin sur trois ans en vue d'un dépistage précoce et d'une institution rapide de la prise en charge. MÉTHODES: Cette étude est une revue rétrospective de trois dépistages hospitaliers ciblés du glaucome : la Journée mondiale de la vue de 2019 (140 participants), la Semaine mondiale du glaucome de 2020 (176 participants) et la Semaine mondiale du glaucome de 2022 (183 participants). Les critères de diagnostic du glaucome et des suspects de glaucome ont été tirés de l'étude nationale sur la prévalence et les types de glaucome de l'enquête nationale nigériane sur la cécité et des critères de la Société internationale de géographie et d'épidémiologie ophtalmologique. RÉSULTATS: La population étudiée avait un âge moyen de 45,54 ans (SD 16,92), les personnes âgées de 51 à 60 ans constituant la majorité des participants (26,4 %). La plupart des participants avaient une vision normale ou une légère déficience visuelle à l'Åil droit (411, 86,1 %) et à l'Åil gauche (405, 84,9 %), tandis que la cécité a été enregistrée à l'Åil droit de 37 participants (7,7 %) et à l'Åil gauche de 36 (7,5 %). La prévalence des cas de glaucome et des suspects de glaucome parmi les participants à l'étude était respectivement de 29,4 % et de 42,5 %. Il existait une relation statistiquement significative entre le diagnostic de glaucome et l'âge avancé, les antécédents familiaux de glaucome et l'élévation de la pression intraoculaire. CONCLUSION: Cette étude a montré que le dépistage ciblé du glaucome est un outil précieux pour assurer la détection précoce de la maladie. MOTS CLÉS: Dépistage du glaucome, Prévalence du glaucome, Cécité due au glaucome, Antécédents familiaux de glaucome.
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Glaucoma , Hospitais de Ensino , Programas de Rastreamento , Humanos , Pessoa de Meia-Idade , Feminino , Masculino , Nigéria/epidemiologia , Estudos Retrospectivos , Glaucoma/diagnóstico , Glaucoma/epidemiologia , Adulto , Programas de Rastreamento/métodos , Prevalência , Idoso , Pressão Intraocular/fisiologia , Adulto JovemRESUMO
The association between dietary selenium intake and glaucoma remains unclear. Using data from the 2005 to 2008 National Health and Nutrition Examination Survey (NHANES), this study aimed to investigate the relationship between glaucoma and dietary selenium intake. The study included subjects aged 40 years or older who participated in the NHANES dietary intake interview and vision health questionnaire. Diagnosis of glaucoma based on self-reporting or fundus imaging. To investigate the relationship between daily selenium consumption and glaucoma, logistic regression analyses were employed. The potential linear relationship was found using smooth curve fitting. Subgroup analyses were also used. We found higher dietary selenium intake was associated with an increased risk of glaucoma (odds ratio, 1.39; 95% confidence intervals,1.07-1.81) on multivariable analysis. A linear association was found between dietary selenium intake and the occurrence of glaucoma in this population (Pnon-linearityâ =â 0.951). Subgroup analyses showed a stable correlation between dietary selenium intake and the occurrence of glaucoma (all P for interactionâ >â .05).This is the first study to look at the connection between dietary selenium intake and glaucoma based on the data from the 2005 to 2008 NHANES. Our findings suggested that dietary selenium intake maybe positively correlated with the risk of glaucoma in adults older than 40 years old. To find out the potential relationship between dietary selenium intake and glaucoma, More longitudinal studies are required.
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Glaucoma , Inquéritos Nutricionais , Selênio , Humanos , Glaucoma/epidemiologia , Feminino , Masculino , Estudos Transversais , Selênio/administração & dosagem , Pessoa de Meia-Idade , Adulto , Idoso , Fatores de Risco , Dieta/estatística & dados numéricosRESUMO
Purpose: This study uses deep neural network-generated rim-to-disc area ratio (RADAR) measurements and the disc damage likelihood scale (DDLS) to measure the rate of optic disc rim loss in a large cohort of glaucoma patients. Methods: A deep neural network was used to calculate RADAR and DDLS for each optic disc photograph (ODP). Patient demographics, diagnosis, intraocular pressure (IOP), and mean deviation (MD) from perimetry were analyzed as risk factors for faster progression of RADAR. Receiver operating characteristic (ROC) curves were used to compare RADAR and DDLS in their utility to distinguish glaucoma from glaucoma suspect (GS) and for detecting glaucoma progression. Results: A total of 13,679 ODPs with evidence of glaucomatous optic nerve damage from 4106 eyes of 2407 patients with glaucoma or GS were included. Of these eyes, 3264 (79.5%) had a diagnosis of glaucoma, and 842 (20.5%) eyes were GS. Mean ± SD baseline RADAR of GS and glaucoma were 0.67 ± 0.13 and 0.57 ± 0.18, respectively (P < 0.001). Older age, greater IOP fluctuation, baseline MD, right eye, and diagnosis of secondary open-angle glaucoma were associated with slope of RADAR. The mean baseline DDLS of GS and glaucoma were 3.78 and 4.39, respectively. Both RADAR and DDLS showed a less steep slope in advanced glaucoma. In glaucoma, the change of RADAR and DDLS correlated with the corresponding change in MD. RADAR and DDLS had a similar ability to discriminate glaucoma from GS and detect disease progression. Area under the ROC curve of RADAR and DDLS was 0.658 and 0.648. Conclusions: Automated calculation of RADAR and DDLS with a neural network can be used to evaluate the extent and long-term rate of optic disc rim loss and is further evidence of long-term nerve fiber loss in treated patients with glaucoma. Translational Relevance: Our study provides a large clinic-based experience for RADAR and DDLS measurements in GS and glaucoma with a neural network.
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Progressão da Doença , Glaucoma , Pressão Intraocular , Redes Neurais de Computação , Disco Óptico , Curva ROC , Humanos , Disco Óptico/patologia , Disco Óptico/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Pressão Intraocular/fisiologia , Glaucoma/diagnóstico , Glaucoma/fisiopatologia , Idoso , Fotografação , Doenças do Nervo Óptico/diagnóstico , Campos Visuais/fisiologia , Testes de Campo Visual/métodos , Adulto , Estudos RetrospectivosRESUMO
Purpose: Crowding is the inability to distinguish objects in the periphery in the presence of clutter. Previous studies showed that crowding is elevated in patients with glaucoma. This could serve as an indicator of the functional visual performance of patients with glaucoma but at present appears too time-consuming and attentionally demanding. We examined visual crowding in individuals with preperimetric glaucoma to compare the potential effectiveness of eye movement-based and manual response paradigms. Methods: We assessed crowding magnitude in 10 participants with preperimetric glaucoma and 10 age-matched controls. Crowding magnitudes were assessed using four different paradigms: a conventional two-alternative forced choice (2AFC) manual, a 2AFC and a six-alternative forced choice (6AFC) eye movement, and a serial search paradigm. All paradigms measured crowding magnitude by comparing participants' orientation discrimination thresholds in isolated and flanked stimulus conditions. Moreover, assessment times and participant preferences were compared across paradigms. Results: Patients with preperimetric glaucoma exhibited elevated crowding, which was most evident in the manual-response paradigm. The serial search paradigm emerged as the fastest method for assessing thresholds, yet it could not effectively distinguish between glaucoma and control groups. The 6AFC paradigm proved challenging for both groups. Conclusions: We conclude that patients with preperimetric glaucoma demonstrate heightened binocular visual crowding. This is most effectively demonstrated via the 2AFC manual response paradigm. The additional attentional demand in eye movement paradigms rendered them less effective in the elderly population of the present study. Translational Relevance: Our findings underscore both the value and the complexity of efficiently evaluating crowding in elderly participants, including those with preperimetric glaucoma.
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Movimentos Oculares , Glaucoma , Campos Visuais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Movimentos Oculares/fisiologia , Idoso , Glaucoma/fisiopatologia , Glaucoma/diagnóstico , Campos Visuais/fisiologia , Testes de Campo Visual/métodos , Acuidade Visual/fisiologia , Limiar Sensorial/fisiologiaRESUMO
The aim of this study was to evaluate the impact of COVID-19 on ocular diseases and changes in risk factors before and after the COVID-19 pandemic. This study was conducted using data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2015-2021, a national cross-sectional health examination and survey. Associations between ocular diseases and risk factors were determined using the chi-squared test and logistic regression analysis. Bivariable adjusted logistic regression analysis was performed to examine the odds ratio (OR) and 95% confidence interval (CI) to evaluate of the impact of COVID-19 on ocular diseases. Individuals were divided into two age groups (< 60 and ≥ 60 years). A total of 50,158 people were diagnosed, of whom 7270 were diagnosed with cataract, 921 with glaucoma, and 439 with age-related macular degeneration (AMD). Risk factors for cataract were COVID-19 pandemic (OR 1.161), hypertension (OR 1.608), diabetes (OR 1.573), dyslipidemia (OR 1.167), stroke (OR 1.272), and depression (OR 1.567). Risk factors for AMD were COVID-19 pandemic (OR 1.600), dyslipidemia (OR 1.610), and depression (OR 1.466). Risk factors for glaucoma were hypertension (OR 1.234), dyslipidemia (OR 1.529), diabetes (OR 1.323), and depression (OR 1.830). The COVID-19 pandemic was a risk factor for cataracts and AMD, but not for glaucoma. Cataracts and AMD may be more influenced by the acquired health conditions or the environment.
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COVID-19 , Catarata , Oftalmopatias , Glaucoma , Degeneração Macular , Humanos , COVID-19/epidemiologia , Pessoa de Meia-Idade , Masculino , Feminino , República da Coreia/epidemiologia , Fatores de Risco , Estudos Transversais , Idoso , Catarata/epidemiologia , Oftalmopatias/epidemiologia , Degeneração Macular/epidemiologia , Adulto , Glaucoma/epidemiologia , Inquéritos Nutricionais , SARS-CoV-2/isolamento & purificação , Pandemias , Idoso de 80 Anos ou maisRESUMO
Background: Ocular comorbidities of hidradenitis suppurativa (HS) has been widely evaluated; however real-world evidence was scarce. Moreover, risk of glaucoma in HS patients remained unclear. This study aimed to evaluate the 5-year glaucoma risk in HS patients. Methods: This retrospective cohort study used the TriNetX database covering 2005-2017. In total, 53,281 HS patients were propensity score matched 1:1 to controls based on demographics, including comorbidities, medications, healthcare utilization, etc. Patients were followed for 5 years post-index date. Glaucoma risks were calculated based on hazard ratios and 95% confidence intervals (95% CI). Stratified analyses by sex and age were performed. Results: After matching, baseline characteristics were similar between groups. HS was associated with a 1.25 times higher 5-year glaucoma risk (95% CI, 1.10-1.42). The risk was significant within 1 year (HR=1.37; 95% CI, 1.03-1.82), 3 years (HR=1.31; 95% CI, 1.12-1.54), and 5 years post-index. In subgroup analysis, women had a 1.28 times higher risk (95% CI, 1.10-1.49). Patients aged 18-64 years (HR=1.33; 95% CI, 1.14-1.55) and ≥65 years (HR=1.33; 95% CI, 1.05-1.67) also presented elevated glaucoma risks. Conclusion: This real-world data analysis demonstrated a significantly increased 5-year glaucoma risk in HS patients versus matched controls. Ocular complications should be concerned while managing HS patients.
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Glaucoma , Hidradenite Supurativa , Pontuação de Propensão , Humanos , Feminino , Masculino , Hidradenite Supurativa/epidemiologia , Hidradenite Supurativa/complicações , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Glaucoma/epidemiologia , Glaucoma/etiologia , Fatores de Risco , Adulto Jovem , Idoso , Comorbidade , Medição de Risco/estatística & dados numéricos , Bases de Dados Factuais/estatística & dados numéricosRESUMO
PRCIS: Severe atopic dermatitis (AD) in patients with glaucoma heightens the risk of requiring surgical intervention, necessitating prompt specialist care and strict surveillance. OBJECTIVE: The impact of AD on the prognosis of patients with glaucoma is rarely studied. This study aims to assess the risk of requiring glaucoma surgery among patients with glaucoma with and without AD. MATERIALS AND METHODS: In this retrospective cohort analysis, we assessed patients with glaucoma initially diagnosed from December 5, 2003 to December 3, 2018 using the TriNetX database, dividing them into AD and non-AD cohorts. 1:1 propensity-score matching created balanced groups for baseline traits and comorbidities. We compared the cohorts' risk and cumulative incidence of needing glaucoma surgery (minimally invasive glaucoma surgery, trabeculectomy, aqueous shunt, or transscleral cyclophotocoagulation). A subgroup analysis was also conducted for patients with severe AD. RESULTS: Out of 528,469 patients with glaucoma, 2624 were in the AD group. Among the AD group, 584 had severe AD. The AD group showed a comparable risk of requiring surgery to the non-AD group (hazard ratio: 1.03; 95% CI: 0.72, 1.47). In contrast, the severe AD group demonstrated a significantly greater risk and cumulative incidence of surgery (hazard ratio: 2.80; 95% CI: 1.37, 5.73; log-rank P = 0.003) compared with the non-AD group. CONCLUSION: Patients with glaucoma with severe AD are significantly more likely to need surgical intervention, with AD severity being a correlating factor for increased risk.
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Dermatite Atópica , Glaucoma , Trabeculectomia , Humanos , Masculino , Feminino , Estudos Retrospectivos , Dermatite Atópica/epidemiologia , Dermatite Atópica/complicações , Dermatite Atópica/cirurgia , Glaucoma/cirurgia , Glaucoma/epidemiologia , Glaucoma/complicações , Pessoa de Meia-Idade , Incidência , Fatores de Risco , Pressão Intraocular/fisiologia , Adulto , Idoso , Implantes para Drenagem de Glaucoma , Saúde GlobalRESUMO
OBJECTIVE: We developed an optimized decision support system for retinal fundus image-based glaucoma screening. METHODS: We combined computer vision algorithms with a convolutional network for fundus images and applied a faster region-based convolutional neural network (FRCNN) and artificial algae algorithm with support vector machine (AAASVM) classifiers. Optic boundary detection, optic cup, and optic disc segmentations were conducted using TernausNet. Glaucoma screening was performed using the optimized FRCNN. The Softmax layer was replaced with an SVM classifier layer and optimized with an AAA to attain enhanced accuracy. RESULTS: Using three retinal fundus image datasets (G1020, digital retinal images vessel extraction, and high-resolution fundus), we obtained accuracy of 95.11%, 92.87%, and 93.7%, respectively. Framework accuracy was amplified with an adaptive gradient algorithm optimizer FRCNN (AFRCNN), which achieved average accuracy 94.06%, sensitivity 93.353%, and specificity 94.706%. AAASVM obtained average accuracy of 96.52%, which was 3% ahead of the FRCNN classifier. These classifiers had areas under the curve of 0.9, 0.85, and 0.87, respectively. CONCLUSION: Based on statistical Friedman evaluation, AAASVM was the best glaucoma screening model. Segmented and classified images can be directed to the health care system to assess patients' progress. This computer-aided decision support system will be useful for optometrists.
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Algoritmos , Fundo de Olho , Glaucoma , Redes Neurais de Computação , Máquina de Vetores de Suporte , Humanos , Glaucoma/diagnóstico , Glaucoma/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Disco Óptico/diagnóstico por imagem , Disco Óptico/patologiaRESUMO
Glaucoma is a blinding disease where the retinal ganglion cells and their axons degenerate. Degradation of axonal microtubules is thought to play a critical role in the pathogenesis, but the mechanism is unknown. Here we investigate whether microtubule disruption in glaucoma can be alleviated by metabolic rescue. The integrity of axonal microtubules and the morphology of the retinal nerve fibers were evaluated by second-harmonic generation microscopy in a mouse model of glaucoma, DBA/2J, which received a dietary supplement of nicotinamide (NAM) for reducing metabolic stress. It was compared with control DBA/2J, which did not receive NAM, and non-glaucomatous DBA/2J-Gpnmb+. We found that the morphology of the retinal nerve fibers, but not axonal microtubules, are significantly protected by NAM. The decoupling is analogous to microtubule deficit, a glaucoma pathology in which axonal microtubules exhibit rapid degradation compared to the morphology of the retinal nerve fibers. Understanding microtubule deficit could provide insights into the divergent responses to NAM. From co-registered images of second-harmonic generation and immunofluorescence, it was determined that microtubule deficit was not due to a shortage of tubulins. Furthermore, microtubule deficit colocalized with the sectors in which the retinal ganglion cells were disconnected from the brain, suggesting that microtubule disruption is associated with axonal transport deficit in glaucoma. Together, our data suggests significant role axonal microtubules play in glaucomatous degeneration, offering a new opportunity for neuroprotection.
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Modelos Animais de Doenças , Glaucoma , Camundongos Endogâmicos DBA , Microtúbulos , Niacinamida , Células Ganglionares da Retina , Animais , Glaucoma/patologia , Glaucoma/metabolismo , Glaucoma/tratamento farmacológico , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Camundongos , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Células Ganglionares da Retina/metabolismo , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Axônios/efeitos dos fármacos , Axônios/metabolismo , Axônios/patologia , Microscopia/métodos , Fibras Nervosas/efeitos dos fármacos , Fibras Nervosas/patologia , Fibras Nervosas/metabolismoRESUMO
The relationship between glaucoma and hypertension is complex. Intraocular pressure is the main modifiable risk factor for glaucoma. Literature describes hypertension as being linked to glaucomatous damage, although the mechanisms are not fully understood. Therefore, glaucoma screening is recommended for hypertensive individuals over 60 years old. The relationships between ocular, arterial pressure, and ocular perfusion pressure, and their impact on optic nerve perfusion, make coordinated management of these elements crucial. Hypertension, hypotension, extreme variability, nocturnal dipping, and overtreatment with antihypertensive drugs can increase the incidence and/or progression of glaucoma. This critical review discusses the causative, clinical, and therapeutic elements to consider in the management of these two pathologies.
La relation entre le glaucome et l'hypertension artérielle (HTA) est complexe. La pression intraoculaire est le principal facteur de risque modifiable du glaucome. Selon la littérature, l'HTA entraînerait un dommage glaucomateux, sans que les mécanismes soient entièrement compris. Le dépistage du glaucome est ainsi recommandé chez les hypertendus de plus 60 ans. La relation entre pression oculaire, artérielle et pression de perfusion oculaire, ainsi que leur impact sur la perfusion du nerf optique, rendent fondamentale la gestion coordonnée de ces deux pathologies. L'HTA, l'hypotension artérielle, la variabilité extrême ou le dipping nocturne, tout comme le surtraitement par antihypertenseurs, peuvent augmenter l'incidence et/ou la progression du glaucome.. Cette revue critique discute des éléments causatifs, cliniques et thérapeutiques à considérer dans la prise en charge de ces deux pathologies.
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Glaucoma , Hipertensão , Humanos , Pessoa de Meia-Idade , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Progressão da Doença , Glaucoma/epidemiologia , Glaucoma/etiologia , Glaucoma/fisiopatologia , Glaucoma/terapia , Hipertensão/complicações , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Hipertensão/terapia , Pressão Intraocular/efeitos dos fármacos , Pressão Intraocular/fisiologia , Fatores de RiscoRESUMO
BACKGROUND: With the advent of targeted therapies, the survival prognosis for metastatic tumors has extended, and it has become necessary to diagnose and consider treatment that takes into account Quality of Life for metastatic tumors of the eye. The reports of checking tumor marker in the aqueous humor for diagnosis of metastatic intraocular tumors are few. Here, we report a case of masquerade syndrome with secondary glaucoma in which a high carcinoembryonic antigen (CEA) level in the aqueous humor could assist diagnosis, and continuing targeted therapy and trabeculectomy were effective. CASE PRESENTATION: A 73-year-old man was referred to us for iritis and high intraocular pressure (IOP) with severe eye pain in the left eye. He had Stage IVB lung adenocarcinoma treated with a molecularly targeted drug, Osimertinib. His best corrected visual acuity was 0.15, and IOP was 52 mmHg in the left eye. Anterior chamber cells (+), numerous small nodules in the iris, and small masses in the inferior angle were observed. In the aqueous humor, the CEA level was higher than in the blood. Napsin A and Thyroid Transcription Factor-1 (TTF-1) positive cells showed in the resected tissue at iridectomy performed during trabeculectomy. The pathological diagnosis of metastatic iris tumor of the lung adenocarcinoma was made, and we injected bevacizumab intravitreally once and continued Osimertinib. His IOP lowered to 8-10 mmHg, and the iris masses disappeared. He lost vision by metastasis to the left optic nerve after termination of Osimertinib one and a half years later. The metastasis shrank after restarting the drug. He passed away from an exacerbation of his primary lung cancer two years and nine months after the first visit. Although he lost vision in his left eye, the metastatic tumor in his left eye and optic nerve had disappeared, and his quality of life was maintained without any pain in his eye. CONCLUSIONS: Checking tumor markers in the aqueous humor can aid in diagnosis, and aggressive treatment of metastatic iris tumors must help maintain patients' Quality of Life.
Assuntos
Humor Aquoso , Antígeno Carcinoembrionário , Neoplasias da Íris , Neoplasias Pulmonares , Humanos , Masculino , Idoso , Neoplasias da Íris/secundário , Neoplasias da Íris/diagnóstico , Neoplasias da Íris/patologia , Humor Aquoso/metabolismo , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Biópsia , Glaucoma/diagnóstico , Trabeculectomia , Adenocarcinoma de Pulmão/secundário , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/análiseRESUMO
Glaucoma is chronic optic neuropathy whose pathogenesis has been associated with the altered metabolism of Trabecular Meshwork Cells, which is a cell type involved in the synthesis and remodeling of the trabecular meshwork, the main drainage pathway of the aqueous humor. Starting from previous findings supporting altered ubiquitin signaling, in this study, we investigated the ubiquitin-mediated turnover of myocilin (MYOC/TIGR gene), which is a glycoprotein with a recognized role in glaucoma pathogenesis, in a human Trabecular Meshwork strain cultivated in vitro in the presence of dexamethasone. This is a validated experimental model of steroid-induced glaucoma, and myocilin upregulation by glucocorticoids is a phenotypic marker of Trabecular Meshwork strains. Western blotting and native-gel electrophoresis first uncovered that, in the presence of dexamethasone, myocilin turnover by proteasome particles was slower than in the absence of the drug. Thereafter, co-immunoprecipitation, RT-PCR and gene-silencing studies identified STUB1/CHIP as a candidate E3-ligase of myocilin. In this regard, dexamethasone treatment was found to downregulate STUB1/CHIP levels by likely promoting its proteasome-mediated turnover. Hence, to strengthen the working hypothesis about global alterations of ubiquitin-signaling, the first profiling of TMCs ubiquitylome, in the presence and absence of dexamethasone, was here undertaken by diGLY proteomics. Application of this workflow effectively highlighted a robust dysregulation of key pathways (e.g., phospholipid signaling, ß-catenin, cell cycle regulation) in dexamethasone-treated Trabecular Meshwork Cells, providing an ubiquitin-centered perspective around the effect of glucocorticoids on metabolism and glaucoma pathogenesis.
Assuntos
Proteínas do Citoesqueleto , Dexametasona , Proteínas do Olho , Glicoproteínas , Complexo de Endopeptidases do Proteassoma , Malha Trabecular , Ubiquitinação , Malha Trabecular/metabolismo , Malha Trabecular/efeitos dos fármacos , Malha Trabecular/citologia , Humanos , Dexametasona/farmacologia , Glicoproteínas/metabolismo , Glicoproteínas/genética , Proteínas do Olho/metabolismo , Proteínas do Olho/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteínas do Citoesqueleto/genética , Células Cultivadas , Ubiquitina/metabolismo , Glaucoma/metabolismo , Glaucoma/patologiaRESUMO
Primary congenital glaucoma (PCG) occurs in children due to developmental abnormalities in the trabecular meshwork and anterior chamber angle. Previous studies have implicated rare variants in CYP1B1, LTBP2, and TEK and their interactions with MYOC, FOXC1, and PRSS56 in the genetic complexity and clinical heterogeneity of PCG. Given that some of the gene-encoded proteins are localized in the centrosomes (MYOC) and perform ciliary functions (TEK), we explored the involvement of a core centrosomal protein, CEP164, which is responsible for ocular development and regulation of intraocular pressure. Deep sequencing of CEP164 in a PCG cohort devoid of homozygous mutations in candidate genes (n = 298) and controls (n = 1757) revealed CEP164 rare pathogenic variants in 16 cases (5.36%). Co-occurrences of heterozygous alleles of CEP164 with other genes were seen in four cases (1.34%), and a physical interaction was noted for CEP164 and CYP1B1 in HEK293 cells. Cases of co-harboring alleles of the CEP164 and other genes had a poor prognosis compared with those with a single copy of the CEP164 allele. We also screened INPP5E, which synergistically interacts with CEP164, and observed a lower frequency of pathogenic variants (0.67%). Our data suggest the potential involvements of CEP164 and INPP5E and the yet unexplored cilia-centrosomal functions in PCG pathogenesis.
Assuntos
Cílios , Citocromo P-450 CYP1B1 , Glaucoma , Humanos , Cílios/genética , Cílios/metabolismo , Cílios/patologia , Masculino , Glaucoma/genética , Glaucoma/congênito , Glaucoma/patologia , Citocromo P-450 CYP1B1/genética , Citocromo P-450 CYP1B1/metabolismo , Feminino , Mutação , Células HEK293 , Criança , Alelos , LactenteRESUMO
Purpose: The purpose of this study was to investigate the large somas presumed to be displaced retinal ganglion cells (dRGCs) located in the inner nuclear layer (INL) of the living human retina. Whereas dRGCs have previously been studied in mammals and human donor tissue, they have never been investigated in the living human retina. Methods: Five young, healthy subjects and three subjects with varying types of glaucoma were imaged at multiple locations in the macula using adaptive optics optical coherence tomography. In the acquired volumes, bright large somas at the INL border with the inner plexiform layer were identified, and the morphometric biomarkers of soma density, en face diameter, and spatial distribution were measured at up to 13 degrees retinal eccentricity. Susceptibility to glaucoma was assessed. Results: In the young, healthy individuals, mean density of the bright, large somas was greatest foveally (550 and 543 cells/mm2 at 2 degrees temporal and nasal, respectively) and decreased with increasing retinal eccentricity (38 cells/mm2 at 13 degrees temporal, the farthest we measured). Soma size distribution showed the opposite trend with diameters and size variation increasing with retinal eccentricity, from 12.7 ± 1.8 µm at 2 degrees to 15.7 ± 3.5 µm at 13 degrees temporal, and showed evidence of a bimodal distribution in more peripheral locations. Within and adjacent to the arcuate defects of the subjects with glaucoma, density of the bright large somas was significantly lower than found in the young, healthy individuals. Conclusions: Our results suggest that the bright, large somas at the INL border are likely comprised of dRGCs but amacrine cells may contribute too. These somas appear highly susceptible to glaucomatous damage.
Assuntos
Glaucoma , Células Ganglionares da Retina , Tomografia de Coerência Óptica , Humanos , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodos , Adulto , Feminino , Masculino , Pessoa de Meia-Idade , Glaucoma/diagnóstico , Idoso , Fibras Nervosas/patologia , Pressão Intraocular/fisiologia , Contagem de Células , Adulto Jovem , Campos Visuais/fisiologia , Voluntários SaudáveisRESUMO
Navigation is essential for moving between locations in our daily lives. We investigated the relationship between visual impairment in glaucoma and path-integration-based navigation. Fourteen glaucoma and 15 controls underwent ophthalmological examination (including visual acuity (logMAR), visual field sensitivity (MD: mean deviation from matched reference cohort), and peripapillary retinal nerve fiber layer (pRNFL)). Both groups navigated physically in virtual reality (VR) environments during daylight and dawn conditions. Briefly, the participants traversed a path marked by three targets, subsequently pointing back to the path's origin. Outcome measures included (i) travel-time, (ii) pointing-time, and (iii) Euclidian-distance error between indicated and starting position. Robust linear regression was conducted between visual function outcomes of the better eye and VR outcome measures. Glaucoma patients showed increase in travel-time (by 8.2 ± 1.7 s; p = 0.002) and in pointing-time (by 5.3 ± 1.6 s; p = 0.016). Predictors were MD for all outcome measures (p < 0.01) and pRNFL for travel-time (p < 0.01). The results suggest that the effect of glaucoma on the elapsed time depends on disease progression, i.e. people with stronger visual impairment need more time. This uncertainty during everyday navigation tasks may adversely affect their quality of life.
Assuntos
Glaucoma , Realidade Virtual , Acuidade Visual , Campos Visuais , Humanos , Feminino , Masculino , Glaucoma/fisiopatologia , Acuidade Visual/fisiologia , Pessoa de Meia-Idade , Campos Visuais/fisiologia , Idoso , Navegação Espacial/fisiologia , Estudos de Casos e ControlesRESUMO
Selective laser trabeculoplasty (SLT), as one of the main methods for the treatment of open-angle glaucoma, has again aroused wide concern in recent years. Although SLT has a clear effect on reducing intraocular pressure, its role needs to be fully recognized. In order to provide guidance for the clinical SLT practice, this article summarizes and discusses the current status of SLT treatment for glaucoma, its therapeutic effects on primary open-angle glaucoma, ocular hypertension, and other types of glaucoma, surgical details, and application prospects.