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.

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.

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.

Prevalence of diabetes mellitus and hypertension among Indian glaucoma patients and evaluation of systemic therapy.

To study the prevalence and systemic control and evaluate the adequacy of therapy of diabetes mellitus (DM) and hypertension (HT) in glaucoma patients visiting a tertiary care eye facility at a university hospital. Consecutive cases with primary open-angle glaucoma (POAG) or primary angle-closure glaucoma (PACG) attending the outpatient services were evaluated for the presence of DM and HT and any systemic/ocular medications being taken were recorded. Of 615 glaucoma cases evaluated, 281 (45.7 %) were POAG and 334 (54.3 %) were PACG. The mean age was 58.19 ± 10.8 years with males comprising 60.5 % of the study group. Two hundred and ninety-two (47.5 %) glaucoma patients had HT and 181 (29.4 %) had DM, including 97 (15.8 %) patients who had both. One hundred and thirty-three (47.3 %) patients with POAG and 159 (47.6 %) patients with PACG had HT. Ninety-seven (34.5 %) POAG patients and 84 (25.1 %) PACG patients were diabetics. One hundred and sixty-one (55.1 %) HT patients had blood pressure above control levels and 88 (48.6 %) diabetics had uncontrolled blood sugars. Twenty-eight (9.6 %) patients with HT were found to be taking combined systemic and topical ß-blocker therapy. A large majority of adult glaucoma patients had concurrent systemic disease, which was not adequately controlled. Patients were using systemic medications with known interactions with ocular hypotensive medications. This study highlights the unmet need for better coordination between ophthalmologists and physicians to improve the overall health of glaucoma patients.

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.

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.

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.

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.

The relationship between components of metabolic syndrome and open-angle glaucoma.

PURPOSE: To determine whether an association exists between various components of metabolic syndrome (diabetes mellitus [DM], systemic arterial hypertension [HTN], hyperlipidemia, and obesity) and open-angle glaucoma (OAG) in a large, diverse group of individuals throughout the United States. DESIGN: Longitudinal cohort study. PARTICIPANTS: All beneficiaries aged ≥40 years continuously enrolled in a managed care network who had 1 or more visits to an eye care provider during 2001 to 2007 were identified. METHODS: Billing codes were used to identify individuals with OAG and those with components of metabolic syndrome. Cox regression was used to determine the hazard of developing OAG in enrollees with individual components or combinations of components of metabolic syndrome, with adjustment for sociodemographic factors, systemic medical conditions, and other ocular diseases. MAIN OUTCOME MEASURES: Hazard of developing OAG. RESULTS: Of the 2 182 315 enrollees who met the inclusion criteria, 55090 (2.5%) had OAG. After adjustment for confounding factors, those with DM (hazard ratio [HR] = 1.35 [95% confidence interval [CI], 1.21-1.50]) or HTN (HR = 1.17 [95% CI, 1.13-1.22]) alone or in combination (HR = 1.48 [95% CI, 1.39-1.58]) had an increased hazard of developing OAG relative to persons with neither of these conditions. By contrast, persons with hyperlipidemia alone had a 5% decreased hazard of OAG (HR = 0.95 [95% CI, 0.91-0.98]). Comorbid hyperlipidemia attenuated the increased hazard between HTN (HR = 1.09 [95% CI, 1.05-1.12]) or DM (HR = 1.13 [95% CI, 1.05-1.21]) and OAG. CONCLUSIONS: At a time when the prevalence of metabolic disorders in the United States, is increasing this study furthers our understanding of risk factors associated with OAG and helps identify persons who may be at increased risk for this condition.

Developing the clinical components of a complex intervention for a glaucoma screening trial: a mixed methods study.

BACKGROUND: Glaucoma is a leading cause of avoidable blindness worldwide. Open angle glaucoma is the most common type of glaucoma. No randomised controlled trials have been conducted evaluating the effectiveness of glaucoma screening for reducing sight loss. It is unclear what the most appropriate intervention to be evaluated in any glaucoma screening trial would be. The purpose of this study was to develop the clinical components of an intervention for evaluation in a glaucoma (open angle) screening trial that would be feasible and acceptable in a UK eye-care service. METHODS: A mixed-methods study, based on the Medical Research Council (MRC) framework for complex interventions, integrating qualitative (semi-structured interviews with 46 UK eye-care providers, policy makers and health service commissioners), and quantitative (economic modelling) methods. Interview data were synthesised and used to revise the screening interventions compared within an existing economic model. RESULTS: The qualitative data indicated broad based support for a glaucoma screening trial to take place in primary care, using ophthalmic trained technical assistants supported by optometry input. The precise location should be tailored to local circumstances. There was variability in opinion around the choice of screening test and target population. Integrating the interview findings with cost-effectiveness criteria reduced 189 potential components to a two test intervention including either optic nerve photography or screening mode perimetry (a measure of visual field sensitivity) with or without tonometry (a measure of intraocular pressure). It would be more cost-effective, and thus acceptable in a policy context, to target screening for open angle glaucoma to those at highest risk but for both practicality and equity arguments the optimal strategy was screening a general population cohort beginning at age forty. CONCLUSIONS: Interventions for screening for open angle glaucoma that would be feasible from a service delivery perspective were identified. Integration within an economic modelling framework explicitly highlighted the trade-off between cost-effectiveness, feasibility and equity. This study exemplifies the MRC recommendation to integrate qualitative and quantitative methods in developing complex interventions. The next step in the development pathway should encompass the views of service users.

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.

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.

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.

The utility of the monocular trial: data from the ocular hypertension treatment study.

OBJECTIVE: To determine whether adjusting the intraocular pressure (IOP) change of the trial eye for the IOP change of the fellow eye (i.e., monocular trial) is a better assessment of medication response than testing each eye independently. DESIGN: Analysis of data from a prospective, randomized, clinical trial. PARTICIPANTS: Two hundred six participants with ocular hypertension randomized to the observation group and later started on a topical prostaglandin analog (PGA). METHODS: Participants were started on a topical PGA in 1 eye and returned in approximately 1 month to determine medication response. The IOP response of the trial eye was determined by the IOP change between baseline and 1 month in the trial eye alone (unadjusted method) and by adjusting for the IOP change in the fellow eye between the same visits (adjusted method). Our "gold standard" for medication response was the IOP change in the trial eye between up to 3 pre- and 3 posttreatment visits on the same medication. Pearson correlation was used to compare the gold standard with the unadjusted and adjusted methods. In addition, symmetry of IOP response between trial and fellow eyes to the same medication was determined by correlating the trial eye IOP change between up to 3 pre- and 3 posttreatment visits to the fellow eye IOP change between the same visits. MAIN OUTCOME MEASURES: Correlations of IOP change of the trial eye using the gold standard to the IOP change of the trial eye using the unadjusted and adjusted methods. RESULTS: The correlations of IOP change using the gold standard to the IOP change using the unadjusted and adjusted methods were r = 0.40 and r = 0.41, respectively. The correlation of IOP change of both eyes between the same pre- and posttreatment visits was r = 0.81. CONCLUSIONS: The monocular trial (i.e., adjusted method) appears equivalent to testing each eye independently (i.e., unadjusted method); however, neither method is adequate to determine medication response to topical PGAs. Both eyes have a similar IOP response to the same PGA. Further studies to understand IOP fluctuation are necessary to improve current methods of assessing medication response. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Glaucoma expert patient programme and ocular hypotensive treatment.

Expert patient programmes (EPPs) are becoming an increasingly important aspect of chronic disease management, resulting in improved health outcomes for patients. Patients with chronic open angle glaucoma (COAG) require lifelong therapy. However, to date, no EPPs have been designed specifically for patients with chronic eye conditions like COAG. This article describes the development and implementation of the Glaucoma Expert Patient Programme (GEPP), a glaucoma-specific educational self-management programme which aims to improve glaucoma patients' knowledge, self-management skills, expectations and adherence to treatment. A review of theoretical frameworks and models which underpin the design, use and conduct of EPPs was undertaken, and the GEPP was designed based on the model by Kate Lorig (2003). The result is an educational programme which offers COAG patients a different perspective on their condition and supports them with knowledge, skills and strategies to better manage their condition on a daily basis.

Presence of crystalline lens as a protective factor for the late development of open angle glaucoma after vitrectomy.

PURPOSE: To evaluate the late development of open angle glaucoma (OAG) after vitrectomy and to compare the rate of postvitrectomy OAG development in phakic and pseudophakic eyes. METHODS: Retrospective case series of 101 eyes of 101 patients who had vitrectomy for idiopathic epiretinal membrane or idiopathic macular hole with a follow-up duration of more than 6 months. Eligible patients were assessed for new development of OAG during the follow-up period. Patients were separated into two groups based on the lens status at the end of the vitrectomy for statistical analysis using Kaplan-Meier survival analysis with log-rank test and Cox regression analysis. RESULTS: The mean follow-up duration was 51 months (range, 6-80 months). Of the 101 eyes, 8 (7.9%) eyes developed OAG during the follow-up period. Phakic eyes were less likely to develop OAG after vitrectomy compared with pseudophakic eyes, with 2% and 13%, respectively (log-rank test, P = 0.025). The result remained statistically significant after adjustment for age, refractive error and the use of gas tamponade (adjusted odds ratio = 0.09, P = 0.038). CONCLUSION: The presence of the crystalline lens may be protective against the late development of OAG after vitrectomy.