Targeting mechanics-induced trabecular meshwork dysfunction through YAP-TGFß Ameliorates high myopia-induced ocular hypertension.

High myopia is a risk factor for primary open angle glaucoma (POAG). The pathological mechanism of high myopia induced POAG occurrence is not fully understood. In this study, we successfully established the guinea pig model of ocular hypertension with high myopia, and demonstrated the susceptibility of high myopia for the occurrence of microbead-induced glaucoma compared with non-myopia group and the effect of YAP/TGF-ß signaling pathway in TM pathogenesis induced by high myopia. Moreover, we performed stretching treatment on primary trabecular meshwork (TM) cells to simulate the mechanical environment of high myopia. It was found that stretching treatment disrupted the cytoskeleton, decreased phagocytic function, enhanced ECM remodeling, and promoted cell apoptosis. The experiments of mechanics-induced human TM cell lines appeared the similar trend. Mechanically, the differential expressed genes of TM cells caused by stretch treatment enriched YAP/TGF-ß signaling pathway. To inhibit YAP/TGF-ß signaling pathway effectively reversed mechanics-induced TM damage. Together, this study enriches mechanistic insights of high myopia induced POAG susceptibility and provides a potential target for the prevention of POAG with high myopia.

Genistein stimulates the viability and prevents myofibroblastic transformation in human trabecular meshwork cells stimulated by TGF-ß.

Primary open-angle glaucoma (POAG) is the most common type of glaucoma leading to blindness. The search for ways to prevent/treat this entity is one of the main challenges of today's ophthalmology. One of such solution seems to be biologically active substances of natural origin, such as genistein (GEN), which can affect the function of isolated trabecular meshwork by the inhibition of protein tyrosine kinase. However, the role of GEN in viability as well as myofibroblastic transformation in human trabecular meshwork cells stimulated by TGF-ß is unknown. Using human trabecular meshwork cells (HTMCs) we investigated the effect of genistein on cell viability and myofibroblastic transformation stimulated by TGF-ß1 and TGF-ß2. Using Real-Time PCR, western blot and immunofluorescence we determined the effect on the expression changes of αSMA, TIMP1, collagen 1 and 3 at mRNA and protein level. We found that genistein increases the viability of HTMCs (1, 2, 3 µg/ml; P < 0.05 and 4, 5, 10, 15, 20 µg/ml; P < 0.01). Moreover, we found that addition of 10, 15 and 20 µg/ml is able to prevent myofibroblastic transformation of HTMCs by decreasing αSMA, TIMP1, collagen 1 and 3 mRNA and protein expression (P < 0.01). Based on the obtained results, we can conclude that genistein is a potential factor that can prevent the myofibroblastic transformation of HTMCs accompanying glaucoma. Describing GEN influence on myofibroblastic transformation processes in HTMC allows us to conclude that it can be considered a potential therapeutic agent or a substance supporting treatment in patients with glaucoma.

Identifying new drugs and targets to treat rapidly elevated intraocular pressure for angle closure and secondary glaucomas to curb visual impairment and prevent blindness.

A multitude of pharmacological compounds have been shown to lower and control intraocular pressure (IOP) in numerous species of animals and human subjects after topical ocular dosing or via other routes of administration. Most researchers have been interested in finding drug candidates that exhibit a relatively long duration of action from a chronic therapeutic use perspective, for example to treat ocular hypertension (OHT), primary open-angle glaucoma and even normotensive glaucoma. However, it is equally important to seek and characterize treatment modalities which offer a rapid onset of action to help provide fast relief from quickly rising IOP that occurs in certain eye diseases. These include acute angle-closure glaucoma, primary angle-closure glaucoma, uveitic and inflammatory glaucoma, medication-induced OHT, and other secondary glaucomas induced by eye injury or infection which can cause partial or complete loss of eyesight. Such fast-acting agents can delay or prevent the need for ocular surgery which is often used to lower the dangerously raised IOP. This research survey was therefore directed at identifying agents from the literature that demonstrated ocular hypotensive activity, normalizing and unifying the data, determining their onset of action and rank ordering them on the basis of rapidity of action starting within 30-60 min and lasting up to at least 3-4 h post topical ocular dosing in different animal species. This research revealed a few health authority-approved drugs and some investigational compounds that appear to meet the necessary criteria of fast onset of action coupled with significant efficacy to reduce elevated IOP (by ≥ 20%, preferably by >30%). However, translation of the novel animal-based findings to the human conditions remains to be demonstrated but represent viable targets, especially EP2-receptor agonists (e.g. omidenepag isopropyl; AL-6598; butaprost), mixed activity serotonin/dopamine receptor agonists (e.g. cabergoline), rho kinase inhibitors (e.g. AMA0076, Y39983), CACNA2D1-gene product inhibitors (e.g. pregabalin), melatonin receptor agonists, and certain K+-channel openers (e.g. nicorandil, pinacidil). Other drug candidates and targets were also identified and will be discussed.

Glucagon-like peptide 1 receptor agonist use is associated with reduced risk for glaucoma.

BACKGROUND/AIMS: Glucagon-like peptide-1 receptor (GLP-1R) agonists regulate blood glucose and are commonly used to treat type 2 diabetes mellitus. Recent work showed that treatment with the GLP-1R agonist NLY01 decreased retinal neuroinflammation and glial activation to rescue retinal ganglion cells in a mouse model of glaucoma. In this study, we used an insurance claims database (Clinformatics Data Mart) to examine whether GLP-1R agonist exposure impacts glaucoma risk. METHODS: A retrospective cohort of patients who initiated a new GLP-1R agonist was 1:3 age, gender, race, classes of active diabetes medications and year of index date matched to patients who initiated a different class of oral diabetic medication. Inverse probability of treatment weighting (IPTW) was used within a multivariable Cox proportional hazard regression model to test the association between GLP-1R agonist exposure and a new diagnosis of primary open-angle glaucoma, glaucoma suspect or low-tension glaucoma. RESULTS: Cohorts were comprised of 1961 new users of GLP-1R agonists matched to 4371 unexposed controls. After IPTW, all variables were balanced (standard mean deviation <|0.1|) between cohorts. Ten (0.51%) new diagnoses of glaucoma were present in the GLP-1R agonist cohort compared with 58 (1.33%) in the unexposed controls. After adjustment, GLP-1R exposure conferred a reduced hazard of 0.56 (95% CI: 0.36 to 0.89, p=0.01), suggesting that GLP-1R agonists decrease the risk for glaucoma. CONCLUSIONS: GLP-1R agonist use was associated with a statistically significant hazard reduction for a new diagnosis of glaucoma. Our findings support further investigations into the use of GLP-1R agonists in glaucoma prevention.

MIND diet lowers risk of open-angle glaucoma: the Rotterdam Study.

PURPOSE: To assess the association between the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet and the incidence of open-angle glaucoma (iOAG), as well as the association between iOAG and two other well-established diets in the Netherlands, i.e., the Mediterranean diet and Dutch dietary guidelines. METHODS: In the Rotterdam Study, participants were followed for iOAG since 1991, with intervals of approximately 5 years. A total of 170 participants developed iOAG during follow-up. Participants with iOAG were matched with healthy controls on age and sex in a case:control ratio of 1:5. The associations between food frequency questionnaire-derived diet adherences (baseline) and iOAG were analyzed using multivariable conditional logistic regression analyses. The associations between the diet adherences and intraocular pressure (IOP; a risk factor for OAG) were assessed using multivariable linear regression analyses. RESULTS: Greater adherence to the MIND diet was associated with a decreased iOAG risk (odds ratio [95% confidence interval]: 0.80 [0.66 to 0.96], for each 10-percent increase in adherence). Food component analyses showed that, in particular a higher intake of green leafy vegetables, berries and fish tended to be protective for iOAG. No significant associations were observed between adherence to the Mediterranean diet or Dutch dietary guidelines and iOAG. Moreover, none of the three examined diets were associated with IOP. CONCLUSION: Adherence to the MIND diet was significantly associated with a lower incidence of OAG in contrast to adherence to the Mediterranean diet or the Dutch dietary guidelines. As this association was IOP-independent, the MIND diet may be particularly relevant for the prevention of neurodegeneration in the eye.

Dietary Nitrate Intake Is Associated with Decreased Incidence of Open-Angle Glaucoma: The Rotterdam Study.

Previous studies suggest that nitric oxide is involved in the regulation of the intraocular pressure (IOP) and in the pathophysiology of open-angle glaucoma (OAG). However, prospective studies investigating the association between dietary nitrate intake, a source of nitric oxide, and incident (i)OAG risk are limited. We aimed to determine the association between dietary nitrate intake and iOAG, and to evaluate the association between dietary nitrate intake and IOP. From 1991 onwards, participants were followed each five years for iOAG in the Rotterdam Study. A total of 173 participants developed iOAG during follow-up. Cases and controls were matched on age (mean ± standard deviation: 65.7 ± 6.9) and sex (%female: 53.2) in a case:control ratio of 1:5. After adjustment for potential confounders, total dietary nitrate intake was associated with a lower iOAG risk (odds ratio (OR) with corresponding 95% confidence interval (95% CI): 0.95 (0.91-0.98) for each 10 mg/day higher intake). Both nitrate intake from vegetables (OR (95% CI): 0.95 (0.91-0.98) for each 10 mg/day higher intake) and nitrate intake from non-vegetable food sources (OR (95% CI): 0.63 (0.41-0.96) for each 10 mg/day higher intake) were associated with a lower iOAG risk. Dietary nitrate intake was not associated with IOP. In conclusion, dietary nitrate intake was associated with a reduced risk of iOAG. IOP-independent mechanisms may underlie the association with OAG.

Potentially Missed Opportunities in Prevention of Acute Angle-Closure Crisis.

Importance: If an anatomic narrow angle is not appropriately diagnosed and treated, it can result in acute angle-closure crisis (AACC) and lead to substantial vision loss. Objective: To identify patients who presented with AACC and assess for factors that may have been associated with risk of developing it. Design, Setting, and Participants: This population-based retrospective cohort study conducted from January 1, 2001, to December 31, 2015, included a 20% nationwide sample of 1179 Medicare beneficiaries. Patients aged 40 years or older with AACC were identified with billing codes. A 2-year lookback period from the date of initial presentation of AACC was used to identify patients who had at least 1 eye care visit, received a diagnosis of open-angle glaucoma (OAG) or suspected OAG, or received at least 1 medication associated with risk of AACC. Of the patients who had at least 1 eye care visit, those who underwent gonioscopy, received a diagnosis of an anatomic narrow angle before developing AACC, or both were identified. Main Outcomes and Measures: Proportions of patients who had at least 1 eye care visit, had OAG or suspected OAG, received at least 1 medication associated with risk of AACC, underwent gonioscopy, or received a diagnosis of an anatomic narrow angle before development of AACC. Results: A total of 1179 patients had a confirmed diagnosis of AACC. The mean (SD) age of patients with AACC was 66.7 (11.8) years (range, 40-96 years), 766 were women (65.0%), 57 were Asian (4.8%), 109 were Black (9.2%), 126 were Latino (10.7%), 791 were White (67.1%), and 96 were other race and ethnicity (8.1%). Of these patients, only 796 (67.5%) consulted an optometrist or ophthalmologist at least once during the 2-year lookback period. A total of 464 individuals (39.4%) had OAG or suspected OAG, and 414 (35.1%) had received at least 1 medication associated with increased risk of AACC before developing it. Of the 796 patients who consulted an optometrist or ophthalmologist in the lookback period, less than one-third underwent gonioscopy in the 2 years before developing AACC (n = 264 [33.2%]), and less than one-half of all patients undergoing gonioscopy received a diagnosis of an anatomic narrow angle (n = 113 [42.8%]). Most patients underwent gonioscopy in the 1 to 4 weeks preceding the AACC. Conclusions and Relevance: In this group of Medicare patients, there appear to have been multiple opportunities for interventions that may have averted AACC. Interventions aimed at addressing risk factors associated with AACC and improving performance of gonioscopy might be associated with reduced risk for ocular morbidity.

Guía de práctica clínica para el manejo de glaucoma de ángulo abierto: guía en versión extensa / Clinical Practice Guideline for the Management of Open-Angle Glaucoma: Comprehensive Version Guide

El tratamiento oportuno de personas con glaucoma primario de ángulo abierto busca minimizar el número de complicaciones por esta enfermedad. Por ello, el Seguro Social de Salud del Perú (EsSalud) priorizó la realización de la presente guía de práctica clínica (GPC) con la finalidad de establecer recomendaciones basadas en evidencia para gestionar de la mejor manera los procesos y procedimientos asistenciales relacionados a esta condición clínica. Esta GPC fue realizada por la Dirección de Guías de Práctica Clínica, Farmacovigilancia y Tecnovigilancia del Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) de EsSalud.

Effect of dietary modification and antioxidant supplementation on intraocular pressure and open-angle glaucoma.

Primary open-angle glaucoma (POAG) is an age-dependent, intraocular pressure (IOP)-related degeneration of the retinal ganglion cells (RGC). At present, IOP is the only modifiable factor that has been identified to prevent glaucomatous vision loss. Though the pathogenesis of glaucomatous optic neuropathy is still not well understood, increasing evidence suggests oxidative stress may contribute to the induction and progression of glaucoma. Furthermore, antioxidant use may be protective against glaucoma through various mechanisms, including reducing IOP, preserving vascular health, and preventing ganglion cell loss. This article provides a comprehensive review of the effect of oxidative stress, diet, and antioxidant therapy on IOP and open-angle glaucoma.

Association of Statin Use and High Serum Cholesterol Levels With Risk of Primary Open-Angle Glaucoma.

Importance: The use of statins (hydroxymethylglutaryl coenzyme A inhibitors) has been associated with a lower risk of primary open-angle glaucoma (POAG); however, results have been conflicting, and little is known about the association between high cholesterol levels and POAG. Objective: To assess the association of elevated cholesterol levels and statin use with incident POAG. Design, Setting, and Participants: This study used data collected biennially from participants aged 40 years or older who were free of glaucoma and reported eye examinations, within 3 population-based cohorts: the Nurses' Health Study (N = 50 710; followed up from 2000 to 2014), the Nurses' Health Study 2 (N = 62 992; 1999-2015), and the Health Professionals Follow-up Study (N = 23 080; 2000-2014). Incident cases of POAG were confirmed by medical record review. The analyses were performed in January 2019. Exposures: Biennially updated self-reported information on elevated cholesterol level status, serum cholesterol levels, and duration of statin use. Main Outcomes and Measures: Multivariable-adjusted relative risks (RRs) and 95% CIs were estimated using Cox proportional hazards regression models on pooled data, with stratification by cohort. Results: Among the 136 782 participants in the 3 cohorts (113 702 women and 23 080 men), 886 incident cases of POAG were identified. Every 20-mg/dL increase in total serum cholesterol was associated with a 7% increase in risk of POAG (RR, 1.07 [95% CI, 1.02-1.11]; P = .004). Any self-reported history of elevated cholesterol was also associated with a higher risk of POAG (RR, 1.17 [95% CI, 1.00-1.37]). A history of any statin use was associated with a 15% lower risk of POAG (RR, 0.85 [95% CI, 0.73-0.99]). Use of statins for 5 or more years vs never use of statins was associated with a 21% lower risk of POAG (RR, 0.79 [95% CI, 0.65-0.97]; P = .02 for linear trend). The association between use of statins for 5 or more years vs never use of statins and risk of POAG was more inverse in those who were older (≥65 years: RR, 0.70 [95% CI, 0.56-0.87] vs <65 years: RR, 1.05 [95% CI, 0.68-1.63]; P = .01 for interaction). Conclusions and Relevance: Among adults aged 40 years or older, higher serum cholesterol levels were associated with higher risk of POAG, while 5 or more years of statin use compared with never use of statins was associated with a lower risk of POAG.

Gene-based sequential burden association test.

Detecting the association between a set of variants and a phenotype of interest is the first and important step in genetic and genomic studies. Although it attracted a large amount of attention in the scientific community and several related statistical approaches have been proposed in the literature, powerful and robust statistical tests are still highly desired and yet to be developed in this area. In this paper, we propose a powerful and robust association test, which combines information from each individual single-nucleotide polymorphisms based on sequential independent burden tests. We compare the proposed approach with some popular tests through a comprehensive simulation study and real data application. Our results show that, in general, the new test is more powerful; the gain in detecting power can be substantial in many situations, compared to other methods.

Assessment of the Impact of an Endpoint Committee in the Ocular Hypertension Treatment Study.

PURPOSE: To assess the impact of a masked Endpoint Committee on estimates of the incidence of primary open-angle glaucoma (POAG) treatment efficacy and statistical power of the Ocular Hypertension Treatment Study-Phase 1, 1994-2002 (OHTS-1). DESIGN: Retrospective interrater reliability analysis of endpoint attribution by the Endpoint Committee. METHODS: After study closeout, we recalculated estimates of endpoint incidence, treatment efficacy, and statistical power using all-cause endpoints and POAG endpoints. To avoid bias, only the first endpoint per participant is included in this report. RESULTS: The Endpoint Committee reviewed 267 first endpoints from 1636 participants. The Endpoint Committee attributed 58% (155 of 267) of the endpoints to POAG. The incidence of all-cause endpoints vs POAG endpoints was 19.5% and 13.2%, respectively, in the observation group and 13.1% and 5.8%, respectively, in the medication group. Treatment effect for all-cause endpoints was a 33% reduction in risk (relative risk = 0.67, 95% confidence interval [CI] of 0.54-0.84) and a 56% reduction in risk for POAG endpoints (relative risk = 0.44, 95% CI of 0.31-0.61). Post hoc statistical power for detecting treatment effect was 0.94 for all-cause endpoints and 0.99 for POAG endpoints. CONCLUSION: Endpoint Committee adjudication of endpoints improved POAG incidence estimates, increased statistical power, and increased calculated treatment effect by 23%. An Endpoint Committee should be considered in therapeutic trials when common ocular and systemic comorbidities, other than the target condition, could compromise study results.

The Effect of Vitamins on Glaucoma: A Systematic Review and Meta-Analysis.

BACKGROUND: The aim of is to determine the association of vitamins with glaucoma by performing a systematic review and meta-analyses. METHODS: Studies on the relation of vitamins and glaucoma published up to December 2017 were identified in the PubMed and Embase database. Data on vitamins (method of assessment), glaucoma (type and method of assessment), study characteristics and quality were recorded. In case of multiple studies for one nutrient a meta-analysis was performed. RESULTS: A total of 629 articles were identified of which 36 were included in the systematic review. The meta-analysis included five of them (940 open-angle glaucoma (OAG) cases and 123,697 controls in total) and resulted in an odds ratio [95% confidence interval] (OR [95% CI]) of 0.58 [0.37-0.91] for dietary vitamin A, though heterogeneity was high (I² = 51%). After omitting studies that contributed significantly to the heterogeneity, the pooled OR [95% CI] was 0.45 [0.30-0.68] for dietary vitamin A on OAG (I² = 0%). For vitamin B1, C and E no significant association with OAG was found (OR [95% CI]: 0.84 [0.47-1.51]; 0.68 [0.38-1.22]; 0.95 [0.75-1.19]; respectively). However, after addressing heterogeneity, vitamin C showed a protective effect as well. Especially, foods high in these vitamins (e.g., dark green vegetables) were protective for OAG. CONCLUSIONS: Dietary intake of vitamin A and C showed a beneficial association with OAG; however, findings on blood levels of vitamins do not show a clear relation with OAG.

Omega-3 fatty acids protect retinal neurons in the DBA/2J hereditary glaucoma mouse model.

The purpose of this study was to evaluate the neuroprotective effects of omega-3 polyunsaturated fatty acid (ω3-PUFA) supplementation, alone or in combination with timolol eye drops, in a mouse model of hereditary glaucoma. DBA/2J mice (8.5-month-old) were assigned to an ω3-PUFAs + timolol, ω3-PUFAs only, timolol only, or an untreated group. Treated mice received a daily gavage administration of eicosapentaenoic acid (EPA) and docosahexaenoic acid and/or topical instillation of timolol (0.5%) once a day for 3 months. Blood was analysed regularly to determine ω3-PUFA levels and retinas were histologically analysed. Real-time PCR and Western blot were performed for retinal pro-inflammatory cytokines and macrophages. Blood arachidonic acid/EPA ratio gradually decreased and reached the desired therapeutic range (1-1.5) after 4 weeks of daily gavage with ω3-PUFAs in the ω3-PUFAs + timolol and ω3-PUFAs only groups. Retinal ganglion cell densities were significantly higher in the ω3-PUFAs + timolol (1303.77 ± 139.62/mm2), ω3-PUFAs only (768.40 ±â€¯52.44/mm2) and timolol only (910.57 ±â€¯57.28/mm2) groups than in the untreated group (323.39 ±â€¯95.18/mm2). ω3-PUFA supplementation alone or timolol alone, significantly increased protein expression levels of M1 macrophage-secreted inducible nitric oxide synthase and M2 macrophage-secreted arginase-1 in the retina, which led to significant decreases in the expression levels of tumour necrosis factor-α (TNF-α). ω3-PUFA supplementation alone also resulted in significantly reduced expression of interleukin-18 (IL-18). ω3-PUFA + timolol treatment had no effect on the expression level of any of the aforementioned mediators in the retina. Supplementation with ω3-PUFAs has neuroprotective effect in the retinas of DBA/2J mice that is enhanced when combined with timolol eye drops. The continued inflammation following ω3-PUFAs + timolol treatment suggests that downregulation of IL-18 and TNF-α may not be the only factors involved in ω3-PUFA-mediated neuroprotection in the retina.

Valoración del uso de retinografía como método de diagnóstico precoz de glaucoma crónico en atención primaria: validación para el cribado en población con factores de riesgo para glaucoma de ángulo abierto / Assessment of the use of retinography as a screening method for the early diagnosis of chronic glaucoma in Primary Care: Validation for screening in populations with open-angle glaucoma risk factors

Objetivo: Determinar la exactitud y el comportamiento de las retinografías realizadas en atención primaria como herramienta de diagnóstico precoz del glaucoma crónico (GAA) en población con factores de riesgo. Diseño: Estudio observacional, descriptivo y transversal con 2 observadores en paralelo de forma ciega: 2 médicos de atención primaria (MAP) y un oftalmólogo de atención especializada Emplazamiento: Centro de atención primaria urbano, consultas externas del servicio de oftalmología (hospitalario). Participantes: Ciento noventa y seis pacientes de ambos sexos, entre 40-70 años, diabéticos, hipertensos, no diagnosticados de glaucoma, captados mediante llamada telefónica tras revisión de listados de pacientes. Dos de los pacientes no acudieron a las citaciones para las pruebas oftalmológicas, considerándose como pérdidas. Mediciones: Para la variable cuantitativa diagnóstico de glaucoma por retinografía: exactitud calculada por la sensibilidad y especificidad, comportamiento por los valores predictivos positivo y negativo, cociente de probabilidad positivo y negativo, concordancia interobservador por índices kappa y cociente de correlación intraclase (CCI). Resultados: Se obtuvo una sensibilidad del 21% (IC 95%: 0-43%), especificidad del 93% (IC 95%: 89-97%), valor predictivo negativo del 94% (IC 95%: 90-97%) y positivo del 20% (IC 95%: 0-40%); cociente de probabilidad positivo de 3,07 (IC 95%: 0,98-9,62) y negativo de 0,84 (IC 95%: 0,64-1,11). El CCI fue de 0,653 (IC 95%: 0,495-0,769), y el índice kappa, de 0,140 (ET: 0,106). Conclusiones: La retinografía no presenta un comportamiento adecuado como herramienta de diagnóstico precoz de GAA desde atención primaria según el modelo planteado en nuestro estudio. Serían necesarios ajustes que subsanasen su baja sensibilidad, como usar otras pruebas combinadas y mejorar el entrenamiento de los MAP (AU)

Objective: The aim of this study is to determine usefulness, validity of retinographies performed in Primary Care as a tool for early diagnosis of open-angle chronic glaucoma (OAG). Design: An observational, descriptive and cross-sectional study with two blinded parallel observers: 2 general practitioners and 1 ophthalmologist. Location: Urban Primary Care Health Centre, and the Ophthalmology Department outpatient clinic. Participants: A total of 196 patients of both genders, between 40-70 years, with diabetes and hypertension, and undiagnosed with glaucoma, were recruited by phone call after checking patient lists. Two patients that did not arrive for their appointments for the ophthalmology tests were considered as losses. Measurements: For the quantitative diagnostic variable of glaucoma: Accuracy calculated from the sensitivity and specificity, safety from the positive and negative predictive values and the positive and negative probability ratio; interobserver concordance by Kappa index ratio and the intraclass correlation (IC). Results: The retinography for OAG screening has a sensitivity of 21% (95% CI: 0-43%), a specificity of 93% (95% CI: 89-97%), a negative predictive value of 94% (95% CI: 90-97%), and positive of 20% (95% CI: 0-40%); positive probability ratio of 3.07 (95% CI: 0.98-9.62) and negative 0.84 (95% CI: 0.64-1.11). The IC was 0.653 (95% CI: 0.495-0.769) and kappa index of 0.140 (0.106 ET). Conclusions: According to this proposed model, retinography is not a useful tool for the early diagnosis of OAG in Primary Care, as it is not safe enough. Before it can be used, it would need adjustments for its low sensitivity, and the use other combined tests. The training of general practitioners would also need to be improved (AU)

Optimizing Glaucoma Screening in High-Risk Population: Design and 1-Year Findings of the Screening to Prevent (SToP) Glaucoma Study.

PURPOSE: To develop, implement, and evaluate a replicable community-based screening intervention designed to improve glaucoma and other eye disease detection and follow-up care in high-risk populations in the United States. We present the design of the study and describe the findings of the first year of the program. DESIGN: Prospective study to evaluate screening and follow-up. METHODS: This is an ongoing study to develop an eye screening program using trained personnel to identify individuals with ophthalmic needs, focusing on African Americans ≥50 years of age at multiple inner-city community sites in Baltimore, Maryland. The screening examination uses a sequential referral approach and assesses presenting visual acuity (VA), best-corrected VA, digital fundus imaging, visual field testing, and measurement of intraocular pressure. RESULTS: We screened 901 individuals between January 2015 and October 2015. Subjects were mostly African Americans (94.9%) with a mean (standard deviation) age of 64.3 (9.9) years. Among them, 356 (39.5%) participants were referred for a definitive eye examination and 107 (11.9%) only needed prescription glasses. The most common reasons for referral were ungradable fundus image (39.3% of those referred), best-corrected VA < 20/40 (14.6%), and ungradable autorefraction (11.8%). Among people referred for definitive examination, 153 (43%) people attended their scheduled examination. The most common diagnoses at the definitive examination were glaucoma and cataract (51% and 40%, respectively). CONCLUSIONS: A large proportion of individuals screened required ophthalmic services, particularly those who were older and less well educated. To reach and encourage these individuals to attend screenings and follow-up examinations, programs could develop innovative strategies and approaches.

Association of Daily Dosage and Type of Statin Agent With Risk of Open-Angle Glaucoma.

IMPORTANCE: There is growing evidence that statins may protect against the development or worsening of open-angle glaucoma (OAG). As researchers plan clinical trials to more definitively study whether statins indeed protect against OAG, it would be helpful to know whether specific daily dosages or types of statin confer a greater protective effect than others. OBJECTIVE: To assess whether the protective effect of statins on the risk of glaucoma varies depending on the daily dosage or type of statin taken. DESIGN, SETTING, AND PARTICIPANTS: Using claims data from January 2001 to December 2009, we observed 25 420 patients with no preexisting glaucoma and quantified exposure to statins and other cholesterol-lowering medications. Using multivariable regression modeling, we assessed the hazard of developing OAG and how it varied by the daily dosage or type of statin and whether any protective effect persists after accounting for baseline low-density lipoprotein level. EXPOSURES: Different daily dosages and types of statins. MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) for developing OAG with 95% CIs. RESULTS: Of the 25 420 patients who met the eligibility criteria for study inclusion, the mean (SD) age was 66.1 (5.8) years, and 14 112 (55.5%) were female. Additionally, 19 232 patients (84.1%) were white, 1252 (5.5%) were black, and 1558 (6.8%) were Latino. After accounting for baseline low-density lipoprotein levels, persons who filled prescriptions for statins continuously for 2 years had a 21% reduced risk of glaucoma compared with nonusers (adjusted HR, 0.79; 95% CI, 0.66-0.96; P = .02). There was no additional protective effect associated with taking the highest dosage of statins (80 mg) compared with a lower dosage (40 mg) (HR, 1.03; 95% CI, 0.59-1.80; P = .91). The protective effect of the following statins on OAG risk did not differ compared with atorvastatin, an inexpensive generic statin: lovastatin (HR, 1.09; 95% CI, 0.71-1.68; P = .69), cerivastatin (HR, 0.61; 95% CI, 0.09-4.41; P = .63), rosuvastatin (HR, 0.83; 95% CI, 0.48-1.44; P = .51), fluvastatin (HR, 0.89; 95% CI, 0.39-2.02; P = .78), pravastatin (HR, 1.29; 95% CI, 0.93-1.79; P = .13), and simvastatin (HR, 1.03; 95% CI, 0.83-1.29; P = .78). CONCLUSIONS AND RELEVANCE: Even after accounting for baseline low-density lipoprotein level, statin exposure continued to be associated with a reduction in OAG risk. Our study helps inform researchers of a reasonable daily dosage and type of statin to use when designing randomized clinical trials to assess the association between statin use and glaucoma.

Pro-fibrotic pathway activation in trabecular meshwork and lamina cribrosa is the main driving force of glaucoma.

While primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide, it still does not have a clear mechanism that can explain all clinical cases of the disease. Elevated IOP is associated with increased accumulation of extracellular matrix (ECM) proteins in the trabecular meshwork (TM) that prevents normal outflow of aqueous humor (AH) and has damaging effects on the fine mesh-like lamina cribrosa (LC) through which the optic nerve fibers pass. Applying a pathway analysis algorithm, we discovered that an elevated level of TGFß observed in glaucoma-affected tissues could lead to pro-fibrotic pathway activation in TM and in LC. In turn, activated pro-fibrotic pathways lead to ECM remodeling in TM and LC, making TM less efficient in AH drainage and making LC more susceptible to damage from elevated IOP via ECM transformation in LC. We propose pathway targets for potential therapeutic interventions to delay or avoid fibrosis initiation in TM and LC tissues.

Is Estrogen a Therapeutic Target for Glaucoma?

This article's objective is to provide an overview of the association between estrogen and glaucoma. A literature synthesis was conducted of articles published in peer-reviewed journals screened through May 5, 2015, using the PubMed database. Keywords used were "estrogen and glaucoma," "reproductive factors and glaucoma," and "estrogen, nitric oxide and eye." Forty-three journal articles were included. Results indicated that markers for lifetime estrogen exposure have been measured by several studies and show that the age of menarche onset, oral contraceptive (OC) use, bilateral oophorectomy, age of menopause onset and duration between menarche to menopause are associated with primary open-angle glaucoma (POAG) risk. The Blue Mountain Eye Study found a significantly increased POAG risk with later (>13 years) compared with earlier (≤12 years) age of menarche. Nurses' Health Study (NHS) investigators found that OC use of greater than 5 years was associated with a 25% increased risk of POAG. The Mayo Clinic Cohort Study of Oophorectomy and Aging found that women who underwent bilateral oophorectomy before age 43 years had an increased risk of glaucoma. The Rotterdam Study found that women who went through menopause before reaching the age of 45 years had a higher risk of open-angle glaucoma (2.6-fold increased risk), while the NHS showed a reduced risk of POAG among women older than 65 who entered menopause after age ≥ 54 years. Increased estrogen states may confer a reduced risk of glaucoma or glaucoma-related traits such as reduced intraocular pressure (IOP). Pregnancy, a hyperestrogenemic state, is associated with decreased IOP during the third trimester. Though the role of postmenopausal hormone (PMH) use in the reduction of IOP is not fully conclusive, PMH use may reduce the risk of POAG. From a genetic epidemiologic perspective, estrogen metabolic pathway single nucleotide polymorphisms (SNPs) were associated with POAG in women and polymorphisms in endothelial nitric oxide synthase, a gene receptive to estrogen regulation, are associated with glaucoma. The study concluded that increasing evidence suggests that lifetime exposure to estrogen may alter the pathogenesis of glaucoma. Estrogen exposure may have a neuroprotective effect on the progression of POAG but further studies need to confirm this finding. The role of sex-specific preventive and therapeutic treatment may be on the horizon.

Control de la presión intraocular en pacientes con glaucoma primario de ángulo abierto y diabetes mellitus / Intraocular pressure control in patients with primary open angle glaucoma and diabetes mellitus

OBJETIVO: Conocer el número de medicamentos empleados para el control de la presión intraocular (PIO) en pacientes con diabetes melitus (DM) y glaucoma primario de ángulo abierto (GPAA), así como las características demográficas de esta población. DISEÑO: Es un estudio observacional, transversal y descriptivo. MÉTODO: Se incluyeron 24 pacientes (47 ojos) con diagnóstico definitivo de DM y GPAA con segumiento de seis meses, registrando sus características demográficas y control de la PIO. RESULTADOS: La edad promedio fue 67,04 ± 8,9 y el 79% correspondió al sexo femenino. El tiempo de diagnóstico de DM fue de 13,87 años y 6,21 años para el GPAA. No hubo diferencia estadísticamente significativa en la agudeza visual inicial y final (p = 0,49). Después de iniciado el tratamiento hubo diferencia entre la PIO inicial y final (p = 0,002), requiriendo 1,9 hipotensores (p < 0,05). Los bloqueadores beta fueron el grupo de medicamentos más empleados como parte de su manejo inicial (41%) y final (28%). CONCLUSIÓN: El control de la PIO en pacientes con DM y GPAA es de 16,8 mm Hg a expensas del uso de 1,9 hipotensores

OBJECTIVE: To determine the number of hypotensive drugs required to control the intraocular pressure (IOP) in patients with primary open angle glaucoma (POAG) and diabetes mellitus (DM), as well as describing their demographic characteristics. DESIGN: Observational, cross-sectional, and descriptive study. METHODS: Twenty four patients (47 eyes) with definitive diagnosis of DM and POAG were included for a six month follow up, recording demographic data and IOP control. RESULTS: The mean age was 67.04 ± 8.9 years, and 79% of patients were female. Mean time from diagnosis of DM was 13.87 years, and 6.21 years for POAG. No statistical difference was observed between initial and final visual acuity (P = 0.49). There was a statistical difference between initial and final IOP once treatment was started (P = 0.002), requiring 1.9 hypotensive drugs (P < 0.05). Beta-blockers were the most used hypotensive drugs for the initial (41%), as well as the final IOP control medication (28%). CONCLUSION: The mean IOP in patients with DM and POAG was 16.8 mm Hg, with the use of 1.9 hypotensive drug