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.

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.

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.

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.

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.

Does cataract surgery reduce the long-term risk of glaucoma in eyes with pseudoexfoliation syndrome?

PURPOSE: To compare glaucoma development and intraocular pressure (IOP) in the longer term following phacoemulsification cataract surgery in eyes with and without pseudoexfoliation syndrome (PEX). METHODS: Fifty-one patients with PEX were compared with 102 age- and gender-matched controls without PEX. Patients were re-examined a mean of 76 (SD 5.4) months after cataract surgery, recording IOP, glaucoma diagnosis, glaucoma treatment and LogMAR. Data from the preoperative visit (baseline) and IOP on the first postoperative day were obtained from medical records. A glaucoma parameter was predefined as patients developing glaucoma or needing increased glaucoma treatment during the postoperative time period. RESULTS: One new glaucoma case in each group was diagnosed postoperatively, yielding glaucoma incidences of 0.47 cases per 100 person-years [95% confidence interval (CI) 0.006-2.61] and 0.17 cases per 100 person-years (CI 0.002-0.95) in the PEX and control groups respectively (p = 0.53). IOP declined by 2.6 (SD 4.0) mmHg in the PEX group (p < 0.001) and 1.9 (SD 3.5) mmHg in the control group (p < 0.001) from baseline to the re-examination, with a non-significant group difference (p = 0.310). IOP spike (≥6 mmHg increase) was significantly associated with the glaucoma parameter, both within the PEX (p = 0.034) and the control group (p = 0.044). CONCLUSION: The number of newly diagnosed glaucoma cases was lower than expected 6-7 years following cataract extraction, especially in the PEX group, which indicates that PEX eyes benefit particularly from cataract surgery in terms of IOP and glaucoma development.

Late postoperative choroidal detachment following an uneventful cataract surgery in a patient on topical latanoprost.

Topical latanoprost is a most effective and commonly used antiglaucoma medication. Use of prostaglandin analogues (PGA) in the early postoperative period is controversial due to its proinflammatory properties. We report a case of a 64-year-old man with primary open angle glaucoma, post-trabeculectomy 17 years prior, with good intraocular pressure (IOP) control on topical levobunolol 0.5% and latanoprost 0.005%. He underwent a clear corneal phacoemulsification surgery in his left eye and the PGA was stopped. He had an uneventful postoperative course and was prescribed eyeglasses at 4-week follow-up. Two weeks later, he presented to the emergency department with decreased vision in the left eye, flat anterior chamber, IOP of 00 mm Hg and 360° choroidal detachment. The continued use of topical latanoprost in the operated eye was implicated as the cause. This case illustrates the serious vision-threatening side effect of PGA when used in the early postoperative period.

A 10-year follow-up to determine the effect of YAG laser iridotomy on the natural history of pigment dispersion syndrome: a randomized clinical trial.

IMPORTANCE: Prospective long-term analyses of the role of drug-induced mydriasis and laser peripheral iridotomy (LPI) are needed to identify and manage the eyes of patients with pigment dispersion syndrome (PDS) at risk for progressing to ocular hypertension. OBJECTIVE: To assess the 10-year incidence of increased intraocular pressure (IOP) in the 2 eyes of patients with PDS, with 1 eye that underwent LPI and the other that did not. DESIGN, SETTING, AND PARTICIPANTS: In a randomized clinical trial in the glaucoma research unit at the University Hospital of Parma, Italy, 72 patients with PDS underwent phenylephrine testing. Of these 72 patients, 29 (58 eyes) tested positive for succeeding IOP elevation, and 43 (59 eyes) tested negative. For the 29 high-risk patients (all in both eyes), one eye was randomly assigned to LPI, and the fellow eye was left untreated. For the 43 low-risk patients, the affected eyes were left untreated. MAIN OUTCOMES AND MEASURES: An IOP elevation of 5 mm Hg or higher vs baseline (daily phasing) was considered to be a significant increase (ie, an event). RESULTS: In the high-risk group, 3 of 21 eyes that underwent LPI (14.3%) and 13 of 21 untreated eyes (61.9%) showed an increase in IOP of 5 mm Hg or higher during the follow-up period; 4 of 35 low-risk eyes (11.4%) showed a similar increase. Event-free mean (SD) time was 7.99 (0.43) years for high-risk treated eyes, 3.89 (0.68) years for high-risk untreated eyes, and 7.16 (0.23) years for low-risk eyes. The log-rank test showed the following: P < .001 for treated high-risk eyes vs untreated high-risk eyes, P = .74 for treated high-risk eyes vs low-risk eyes, and P < .001 for untreated high-risk eyes vs low-risk eyes. CONCLUSIONS AND RELEVANCE: At the end of the 10-year follow-up, (1) approximately one-third of the whole PDS patient population showed an IOP increase of 5 mm Hg or higher in at least 1 eye; (2) phenylephrine testing identified eyes at high risk for developing IOP elevation; and (3) LPI, when performed on high-risk eyes, reduced the rate of IOP elevation to the same level as the low-risk eyes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01053416.

Ocular-specific ER stress reduction rescues glaucoma in murine glucocorticoid-induced glaucoma.

Administration of glucocorticoids induces ocular hypertension in some patients. If untreated, these patients can develop a secondary glaucoma that resembles primary open-angle glaucoma (POAG). The underlying pathology of glucocorticoid-induced glaucoma is not fully understood, due in part to lack of an appropriate animal model. Here, we developed a murine model of glucocorticoid-induced glaucoma that exhibits glaucoma features that are observed in patients. Treatment of WT mice with topical ocular 0.1% dexamethasone led to elevation of intraocular pressure (IOP), functional and structural loss of retinal ganglion cells, and axonal degeneration, resembling glucocorticoid-induced glaucoma in human patients. Furthermore, dexamethasone-induced ocular hypertension was associated with chronic ER stress of the trabecular meshwork (TM). Similar to patients, withdrawal of dexamethasone treatment reduced elevated IOP and ER stress in this animal model. Dexamethasone induced the transcriptional factor CHOP, a marker for chronic ER stress, in the anterior segment tissues, and Chop deletion reduced ER stress in these tissues and prevented dexamethasone-induced ocular hypertension. Furthermore, reduction of ER stress in the TM with sodium 4-phenylbutyrate prevented dexamethasone-induced ocular hypertension in WT mice. Our data indicate that ER stress contributes to glucocorticoid-induced ocular hypertension and suggest that reducing ER stress has potential as a therapeutic strategy for treating glucocorticoid-induced glaucoma.

The potential association between postmenopausal hormone use and primary open-angle glaucoma.

IMPORTANCE: Retinal ganglion cells are known to express estrogen receptors and prior studies have suggested an association between postmenopausal hormone (PMH) use and decreased intraocular pressure, suggesting that PMH use may decrease the risk for primary open-angle glaucoma (POAG). OBJECTIVE: To determine whether the use of 3 different classes of PMH affects the risk for POAG. DESIGN, SETTING, AND PARTICIPANTS: Retrospective longitudinal cohort analysis of claims data from women 50 years or older enrolled in a US managed-care plan for at least 4 years in which enrollees had at least 2 visits to an eye care provider during the period 2001 through 2009. EXPOSURE: Postmenopausal hormone medications containing estrogen only, estrogen + progesterone, and estrogen + androgen, as captured from outpatient pharmacy claims over a 4-year period. MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) for developing incident POAG. RESULTS: Of 152,163 eligible enrollees, 2925 (1.9%) developed POAG. After adjustment for confounding factors, each additional month of use of PMH containing estrogen only was associated with a 0.4% reduced risk for POAG (HR, 0.996 [95% CI, 0.993-0.999]; P = .02). The risk for POAG did not differ with each additional month of use of estrogen + progesterone (HR, 0.994 [95% CI, 0.987-1.001]; P = .08) or estrogen + androgen (HR, 0.999 [95% CI, 0.988-1.011]; P = .89). CONCLUSIONS AND RELEVANCE: Use of PMH preparations containing estrogen may help reduce the risk for POAG. If prospective studies confirm the findings of this analysis, novel treatments for this sight-threatening condition may follow.

Sinais e sintomas de doença da superfície ocular em usuários de hipotensores oculares tópicos / Signs and symptoms of ocular surface disease in patients on topical intraocular pressure-lowering therapy

OBJETIVO: determinar a prevalência de sinais e sintomas de doença da superfície ocular (OSD) em pacientes em uso crônico de hipotensores oculares tópicos. MÉTODOS: Neste estudo transversal, foram recrutados 40 pacientes consecutivos, provenientes do ambulatório de glaucoma de um hospital público localizado no Rio de Janeiro, Brasil. Os mesmos deveriam apresentar: idade maior ou igual a 18 anos, diagnóstico de hipertensão ocular ou glaucoma primário de ângulo aberto e deveriam estar em uso da mesma terapia hipotensora ocular há pelo menos seis meses. Foram considerados: sexo, idade, medicação utilizada e duração do tratamento. Todos os pacientes foram submetidos à avaliação da superfície ocular que incluiu: entrevista por meio do questionário Ocular Surface Disease Index® (OSDI®), tempo de rotura do filme lacrimal, biomicroscopia, avaliação da superfície ocular com fluoresceína e com rosa Bengala. RESULTADOS: A média de pontuação do OSDI® foi 24,6 ± 20,7. A maioria dos pacientes (67,5%) apresentou uma pontuação anormal no questionário do OSDI®. Em 25% dos pacientes, a pontuação foi compatível com sintomas leves, em 12,5% com sintomas moderados e em 30% com sintomas graves. Blefarite e ceratite ponteada foram diagnosticadas em 42,5% e 20% dos pacientes respectivamente. Instabilidade do filme lacrimal foi observada em 75% dos pacientes, enquanto que alteração da superfície ocular foi evidenciada pelo teste de rosa bengala em 35% dos pacientes. Foi encontrada correlação positiva (r=0,4) estatisticamente significativa (p=0,01) entre a pontuação do OSDI® e o tempo de duração do tratamento com hipotensores oculares tópicos. CONCLUSÃO: Pacientes em uso crônico de hipotensores oculares tópicos apresentam alta prevalência de sinais e sintomas de OSD. Existe correlação significativa entre a duração do tratamento e a gravidade dos sintomas de OSD.

PURPOSE: To determine the prevalence of signs and symptoms of ocular surface disease (OSD) in patients using topical intraocular pressure-lowering therapy. METHODS: In this cross-sectional study, 40 patients were consecutively recruited from the glaucoma clinic of a public hospital located in Rio de Janeiro, Brazil. Eligible patients were 18 years of age or older, with primary open-angle glaucoma or ocular hypertension and on the same topical ocular therapy for at least 6 months. The following data were considered: sex, age, medication history and number of years on topical intraocular pressure-lowering therapy. All patients underwent an evaluation of the ocular surface which included: an interview using the Ocular Surface Disease Index® (OSDI®) questionnaire, break-up time, biomicroscopy, fluorescein corneal staining and rose Bengal ocular surface staining. RESULTS: The mean OSDI® score was 24.6 ± 20.7. Most patients (67.5%) had an abnormal score on the OSDI® questionnaire. In 25% of patients, the score was consistent with mild symptoms, 12.5% ​​with moderate symptoms and 30% with severe symptoms. Blepharitis and punctate keratitis were diagnosed in 42.5% and 20% of patients respectively. Tear film instability was observed in 75% of patients and ocular surface staining with rose Bengal in 35%. A positive statistically significant correlation (r=0.4; p=0.01) was found between OSDI® scores and the duration of topical intraocular pressure-lowering therapy. CONCLUSION: Patients with primary open-angle glaucoma or ocular hypertension on topical intraocular pressure-lowering therapy have high prevalence of OSD. Longer duration since diagnosis is significantly correlated with worsening of OSD symptoms.

Canadian Journal of Ophthalmology Lecture: translational research advances in glaucoma neuroprotection.

Given that glaucoma is a disease of the central nervous system, there must be greater emphasis and focus on developing intraocular pressure-independent therapies. In addition, scientific research investigating the role of sustained drug delivery is critical for advancing the field. Exciting innovation will require close collaboration and full integration of clinical and basic research efforts. Thus, translational research advances in neuroprotection may lead to future development of truly revolutionary therapies for glaucoma (e.g., neuroregeneration).

Surveillance for ocular hypertension: an evidence synthesis and economic evaluation.

OBJECTIVES: To determine effective and efficient monitoring criteria for ocular hypertension [raised intraocular pressure (IOP)] through (i) identification and validation of glaucoma risk prediction models; and (ii) development of models to determine optimal surveillance pathways. DESIGN: A discrete event simulation economic modelling evaluation. Data from systematic reviews of risk prediction models and agreement between tonometers, secondary analyses of existing datasets (to validate identified risk models and determine optimal monitoring criteria) and public preferences were used to structure and populate the economic model. SETTING: Primary and secondary care. PARTICIPANTS: Adults with ocular hypertension (IOP > 21 mmHg) and the public (surveillance preferences). INTERVENTIONS: We compared five pathways: two based on National Institute for Health and Clinical Excellence (NICE) guidelines with monitoring interval and treatment depending on initial risk stratification, 'NICE intensive' (4-monthly to annual monitoring) and 'NICE conservative' (6-monthly to biennial monitoring); two pathways, differing in location (hospital and community), with monitoring biennially and treatment initiated for a ≥ 6% 5-year glaucoma risk; and a 'treat all' pathway involving treatment with a prostaglandin analogue if IOP > 21 mmHg and IOP measured annually in the community. MAIN OUTCOME MEASURES: Glaucoma cases detected; tonometer agreement; public preferences; costs; willingness to pay and quality-adjusted life-years (QALYs). RESULTS: The best available glaucoma risk prediction model estimated the 5-year risk based on age and ocular predictors (IOP, central corneal thickness, optic nerve damage and index of visual field status). Taking the average of two IOP readings, by tonometry, true change was detected at two years. Sizeable measurement variability was noted between tonometers. There was a general public preference for monitoring; good communication and understanding of the process predicted service value. 'Treat all' was the least costly and 'NICE intensive' the most costly pathway. Biennial monitoring reduced the number of cases of glaucoma conversion compared with a 'treat all' pathway and provided more QALYs, but the incremental cost-effectiveness ratio (ICER) was considerably more than £30,000. The 'NICE intensive' pathway also avoided glaucoma conversion, but NICE-based pathways were either dominated (more costly and less effective) by biennial hospital monitoring or had a ICERs > £30,000. Results were not sensitive to the risk threshold for initiating surveillance but were sensitive to the risk threshold for initiating treatment, NHS costs and treatment adherence. LIMITATIONS: Optimal monitoring intervals were based on IOP data. There were insufficient data to determine the optimal frequency of measurement of the visual field or optic nerve head for identification of glaucoma. The economic modelling took a 20-year time horizon which may be insufficient to capture long-term benefits. Sensitivity analyses may not fully capture the uncertainty surrounding parameter estimates. CONCLUSIONS: For confirmed ocular hypertension, findings suggest that there is no clear benefit from intensive monitoring. Consideration of the patient experience is important. A cohort study is recommended to provide data to refine the glaucoma risk prediction model, determine the optimum type and frequency of serial glaucoma tests and estimate costs and patient preferences for monitoring and treatment. FUNDING: The National Institute for Health Research Health Technology Assessment Programme.

The relationship between statin use and open-angle glaucoma.

PURPOSE: To determine whether 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) affect the risk of developing open-angle glaucoma (OAG) in persons with hyperlipidemia. DESIGN: Retrospective, longitudinal cohort analysis. PARTICIPANTS: Individuals aged ≥60 years with hyperlipidemia enrolled in a national United States managed care network between 2001 and 2009. METHODS: Multivariable Cox regression analyses were performed to assess the relationship between statin use and the development of OAG (from no prior OAG diagnosis), progression from a prior diagnosis of glaucoma suspect to a diagnosis of OAG, and need for medical or operative interventions for OAG. Regression models were adjusted for sociodemographic factors and medical and ocular comorbidities. MAIN OUTCOME MEASURES: Hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Of the 524 109 individuals with hyperlipidemia, 316 182 (60%) had ≥1 outpatient prescription for statins. The hazard of developing OAG decreased 0.3% (adjusted HR, 0.997; 95% CI 0.994-0.999) for every additional month of statin consumption. Individuals with hyperlipidemia who took statins continuously for 2 years had an 8% (adjusted HR, 0.922; 95% CI, 0.870-0.976) decreased OAG risk relative to those who received no statin therapy. The hazard of progressing from a diagnosis of glaucoma suspect to OAG decreased 0.4% (adjusted HR, 0.996; 95% CI, 0.993-0.999) for every additional month of statin exposure. Individuals who took statins continuously for 2 years had a 9% (adjusted HR, 0.907; 95% CI, 0.846-0.973) decreased risk of progressing from glaucoma suspect to OAG relative to those who received no statin therapy. The hazard of requiring medical treatment for OAG decreased 0.4% (adjusted HR, 0.996; 95% CI, 0.993-0.998) for every additional month of statin exposure. No differences in need for glaucoma surgery were noted among those with OAG who were and were not taking statins (adjusted HR, 1.002; 95% CI, 0.994-1.010). CONCLUSIONS: Statin use was associated with a significant reduction in the risk of OAG among persons with hyperlipidemia. Given the mounting evidence of statin protection against OAG including both basic science and observational clinical studies, an interventional prospective study might provide additional insights into the role of statins in the prevention of early OAG.

Reduction in intraocular pressure after cataract extraction: the Ocular Hypertension Treatment Study.

PURPOSE: To determine the change in intraocular pressure (IOP) after cataract extraction in the observation group of the Ocular Hypertension Treatment Study. DESIGN: Comparative case series. PARTICIPANTS: Forty-two participants (63 eyes) who underwent cataract surgery in at least 1 eye during the study and a control group of 743 participants (743 eyes) who did not undergo cataract surgery. METHODS: We defined the "split date" as the study visit date at which cataract surgery was reported in the cataract surgery group and a corresponding date in the control group. Preoperative IOP was defined as the mean IOP of up to 3 visits before the split date. Postoperative IOP was the mean IOP of up to 3 visits including the split date (0, 6, and 12 months' with "0 months" equaling the split date). In both groups, we censored data after initiation of ocular hypotensive medication or glaucoma surgery of any kind. MAIN OUTCOME MEASURES: Difference in preoperative and postoperative IOP. RESULTS: In the cataract group, postoperative IOP was significantly lower than the preoperative IOP (19.8 ± 3.2 mmHg vs. 23.9 ± 3.2 mmHg; P<0.001). The postoperative IOP remained lower than the preoperative IOP for at least 36 months. The average decrease in postoperative IOP from preoperative IOP was 16.5%, and 39.7% of eyes had postoperative IOP ≥ 20% below preoperative IOP. A greater reduction in postoperative IOP occurred in the eyes with the highest preoperative IOP. In the control group, the corresponding mean IOPs were 23.8 ± 3.6 before the split date and 23.4 ± 3.9 after the split date. CONCLUSIONS: Cataract surgery decreases IOP in patients with ocular hypertension over a long period of time.

Glaucoma in the English-speaking Caribbean.

The Barbados Eye Studies have provided the most comprehensive information on the major eye diseases in African origin populations to date. Black Barbadians have among the highest rates of primary open-angle glaucoma (OAG) reported to date in a population-based study (7.0%). Incidence rates of OAG over a nine-year follow-up period were 0.5% per year, and two to five times higher than reported in predominantly Caucasian populations. Risk factors for OAG included older age, male gender higher intraocular pressure, positive glaucoma family history, in addition to lean body mass and a positive cataract history. Low blood pressure to intraocular pressure relationships were also found to increase OAG risk, suggesting an aetiologic role for low vascular perfusion of the optic nerve. Recent analyses revealed a region on chromosome 2 associated with increased OAG risk, which has potential implications for early diagnosis and treatment. Approximately 50% of Barbadians with OAG were unaware of having the disease in the baseline study and this situation remained unchanged nine years later open-angle glaucoma causes painless, irreversible loss of vision and there are clear reasons why screening may be of particular public health importance in high risk African descent populations, given the benefits of early detection and appropriate treatment. There are data that suggest that it would be cost-effective to conduct open-angle glaucoma screening in Barbados and this has implications for policy and care, with the ultimate aim of reducing glaucoma-related blindness.

Physical activity and ocular perfusion pressure: the EPIC-Norfolk eye study.

PURPOSE: To examine the relationship between physical activity and ocular perfusion pressure (OPP), a consistent risk factor for glaucoma. METHODS: The relationship between previous physical activity and current OPP in 5650 participants aged 48 to 90 who attended the first (1993-1997) and third (2006-2010) health check as part of the European Prospective Investigation into Cancer (EPIC)-Norfolk study was examined. Usual combined physical activity at work and leisure was assessed using a validated instrument. Individuals were categorized as inactive, moderately inactive, moderately active, or active. Three IOP measurements were obtained (Ocular Response Analyzer [ORA]; Reichert, Inc., Depew, NY). Mean Goldmann correlated IOP (IOPg) from one eye was used in the analysis. Systolic and diastolic blood pressure (BP) were recorded as the mean of two measurements taken with a sphygmomanometer. Associations between physical activity and low (≤40 mm Hg) mean OPP (2/3 mean arterial pressure - IOP) and low (≤50 mm Hg) diastolic OPP (diastolic BP - IOP) were tested using logistic regression, adjusting for age, sex, body mass index, social class, IOP, and BP. RESULTS: Active people had a lower risk of mean OPP ≤ 40 mm Hg and diastolic OPP ≤ 50 mm Hg after adjusting for age, sex, social class, and body mass index (odds ratio, 0.75; 95% confidence interval [CI], 0.60-0.93; P < 0.01) and (odds ratio, 0.73, 95% CI, 0.58-0.93; P = 0.01), respectively. The association between physical activity and perfusion pressure was independent of IOP, but largely mediated through diastolic BP. CONCLUSIONS: Lower levels of physical activity were associated with lower OPP. Further research is needed to investigate the potential benefit of increased physical activity as a safe and simple method of modifying glaucoma risk.

Risk factors for glaucoma: what do they really mean?

Glaucoma is an insidious eye disease, potentially putting 4% of older Australians at risk of blindness, unless detected sufficiently early for initiation of effective treatment. This paper reports on the strengths of evidence and glaucoma risk factors that can be identified by primary health care providers from a patient's history. A comprehensive search of peer-reviewed databases identified relevant secondary evidence published between 2002 and 2007. Risk factors that could be determined from a patient's history were identified. A novel glaucoma risk factor reference guide was constructed according to evidence strength and level of concern regarding risk of developing glaucoma. The evidence is strong and consistent regarding the risk of developing glaucoma, and elevated intraocular pressure, advancing age, non-Caucasian ethnicity and family history of glaucoma. There is moderate evidence of association with glaucoma, and migraine, eye injury, myopia and long-term use of corticosteroids. There is conflicting evidence for living in a rural location, high blood pressure, diabetes and smoking. Early detection of people at risk of developing glaucoma can be initiated using our risk factor guide coupled with a comprehensive patient history. Timely future assessment and subsequent management strategies for at-risk individuals can then be effectively and efficiently actioned.

Glaucoma in the English-speaking Caribbean / El glaucoma en el Caribe Anglófono

The Barbados Eye Studies have provided the most comprehensive information on the major eye diseases in African origin populations to date. Black Barbadians have among the highest rates of primary open-angle glaucoma (OAG) reported to date in a population-based study (7.0%). Incidence rates of OAG over a nine-year follow-up period were 0.5% per year, and two to five times higher than reported in predominantly Caucasian populations. Risk factors for OAG included older age, male gender, higher intraocular pressure, positive glaucoma family history, in addition to lean body mass and a positive cataract history. Low blood pressure to intraocular pressure relationships were also found to increase OAG risk, suggesting an aetiologic role for low vascular perfusion of the optic nerve. Recent analyses revealed a region on chromosome 2 associated with increased OAG risk, which has potential implications for early diagnosis and treatment. Approximately 50% of Barbadians with OAG were unaware of having the disease in the baseline study and this situation remained unchanged nine years later. Open-angle glaucoma causes painless, irreversible loss of vision and there are clear reasons why screening may be of particular public health importance in high risk African descent populations, given the benefits of early detection and appropriate treatment. There are data that suggest that it would be cost-effective to conduct Open-angle glaucoma screening in Barbados and this has implications for policy and care, with the ultimate aim of reducing glaucoma-related blindness.

Los Estudios Oftalmológicos de Barbados han proporcionado la información más integral sobre las principales enfermedades oculares en las poblaciones de origen africano hasta la fecha. Los barbadenses negros se cuentan entre las poblaciones con tasas más altas de glaucoma de ángulo abierto (GAA) hasta la fecha, según un estudio de base poblacional realizado (7.0%). Las tasas de incidencia de GAA en un período de seguimiento de nueve años, fueron 0.5% por año - de dos a cinco veces mayores que las reportadas predominantemente en poblaciones caucásicas. Los factores de riesgo para el GAA incluyeron los años de edad, el ser varón, el tener presión intraocular alta, y una historia de pruebas positivas de glaucoma en la familia, además pobre masa corporal, y una historia positiva de catarata. Se halló que las relaciones de baja presión sanguínea con respecto a la presión intra-ocular, aumentan el riesgo de GAA, sugiriendo así un papel etiológico a la bajo perfusión vascular del nervio óptico. Recientes análisis revelaron una región en el cromosoma dos, asociada con el aumento de riesgo del GAA, con implicaciones potenciales para un diagnóstico y tratamiento tempranos. Aproximadamente el 50% de los barbadenses con GAA no tenían conciencia de tener la enfermedad en el estudio inicial de partida, y esta situación permanecería invariable nueve años más tarde. El glaucoma de ángulo abierto causa una pérdida sin dolor e irreversible de la visión, y hay razones claras por las que el tamizaje puede revestir particular importancia para la salud pública de poblaciones de ascendencia africana en alto riesgo, dados los beneficios de una detección precoz y un tratamiento adecuado. Hay datos que sugieren que sería costo-efectivo llevar a cabo un tamizaje del GAA en Barbados, lo cual tendría implicaciones tanto en relación con las políticas a seguir cuanto para la atención misma, cuyo objetivo final reducir la ceguera relacionada con el glaucoma.