Common genetic determinants of intraocular pressure and primary open-angle Glaucoma

10.1371/journal.pgen.1002611PLoS Genetics85

Number of People Blind or Visually Impaired by Glaucoma Worldwide and in World Regions 1990 – 2010: A Meta-Analysis

Objective: To assess the number of individuals visually impaired or blind due to glaucoma and to examine regional differences and temporal changes in this parameter for the period from 1990 to 2012. Methods: As part of the Global Burden of Diseases (GBD) Study 2010, we performed a systematic literature review for the period from 1980 to 2012. We primarily identified 14,908 relevant manuscripts, out of which 243 high-quality, population-based studies remained after review by an expert panel that involved application of selection criteria that dwelt on population representativeness and clarity of visual acuity methods used. Sixty-six specified the proportion attributable to glaucoma. The software tool DisMod-MR (Disease Modeling–Metaregression) of the GBD was used to calculate fraction of vision impairment due to glaucoma. Results: In 2010, 2.1 million (95% Uncertainty Interval (UI):1.9,2.6) people were blind, and 4.2 (95% UI:3.7,5.8) million were visually impaired due to glaucoma. Glaucoma caused worldwide 6.6% (95% UI:5.9,7.9) of all blindness in 2010 and 2.2% (95% UI:2.0,2.8) of all moderate and severe visual impairment (MSVI). These figures were lower in regions with younger populations (10%). From 1990 to 2010, the number of blind or visually impaired due to glaucoma increased by 0.8 million (95%UI:0.7, 1.1) or 62% and by 2.3 million (95%UI:2.1,3.5) or 83%, respectively. Percentage of global blindness caused by glaucoma increased between 1990 and 2010 from 4.4% (4.0,5.1) to 6.6%. Age-standardized prevalence of glaucoma related blindness and MSVI did not differ markedly between world regions nor between women. Significance: By 2010, one out of 15 blind people was blind due to glaucoma, and one of 45 visually impaired people was visually impaired, highlighting the increasing global burden of glaucoma

Consequences of HIV for children: avoidable or inevitable?

The HIV/AIDS epidemic has many serious consequences for children. These consequences are, however, rarely inevitable. Families can provide a protective barrier that deflects blows, or minimises their impact and a supportive nurturing environment that can help children recover from harm. If strong enough, and with sufficient access to quality services and support from communities, families can reduce the impacts of HIV/AIDS on children to negligible levels in most areas of impact. It is apparent that the impacts felt by children are not simply unfortunate, inevitable consequences of this epidemic. A strong and supported family with good access to quality services can deflect almost all of the impact. It is as a result of an interaction of the context of poverty, which weakens families, and a failure to adequately respond, that impacts are felt by children

European Glaucoma Society research priorities for glaucoma care

Background/Aims: The goal of health research is to improve patients care and outcomes. Thus, it is essential that research addresses questions that are important to patients and clinicians. The aim of this study was to develop a list of priorities for glaucoma research involving stakeholders from different countries in Europe. Methods: We used a three-phase method, including a two-round electronic Delphi survey and a workshop. The clinician and patient electronic surveys were conducted in parallel and independently. For phase I, the survey was distributed to patients from 27 European countries in 6 different languages, and to European Glaucoma Society members, ophthalmologists with expertise in glaucoma care, asking to name up to five research priorities. During phase II, participants were asked to rank the questions identified in phase I using a Likert scale. Phase III was a 1 day workshop with patients and clinicians. The purpose was to make decisions about the 10 most important research priorities using the top 20 priorities identified by patients and clinicians. Results: In phase I, 308 patients and 150 clinicians were involved. In phase II, the highest-ranking priority for both patients and clinicians was € treatments to restore vision'. In phase III, eight patients and four clinicians were involved. The top three priorities were € treatments to stop sight loss', € treatments to restore vision' and € improved detection of worsening glaucoma'. Conclusion: We have developed a list of priorities for glaucoma research involving clinicians and patients from different European countries that will help guide research efforts and investment

The effect of citicoline oral solution on quality of life in patients with glaucoma: the results of an international, multicenter, randomized, placebo-controlled cross-over trial

PURPOSE: This study aims to evaluate whether the use of citicoline oral solution could improve quality of life in patients with chronic open-angle glaucoma (OAG). DESIGN: Randomized, double-masked, placebo-controlled, cross-over study was used. Patients were randomized to one of the two sequences: either citicoline 500 mg/day oral solution-placebo or placebo-citicoline 500 mg/day oral solution. Switch of treatments was done after 3 months; patients were then followed for other 6 months. Follow-up included 3-month, 6-month, and 9-month visits. OUTCOMES: The primary outcome was the mean change of "intra-patient" composite score of the Visual Function Questionnaire-25 (VFQ-25). after citicoline oral solution vs placebo at 6-month visit as compared with baseline. METHODS: The trial was multicenter, conducted at 5 European Eye Clinics. OAG patients with bilateral visual field damage, a mean deviation (MD) ranging from - 5 to - 13 dB in the better eye, and controlled IOP were included. VFQ-25 and SF-36 questionnaires were administered at baseline and at 3-, 6-, and 9-month visits. A mixed effect model, with a random effect on the intercept, accounted for correlations among serial measurements on each subject. RESULTS: The primary pre-specified outcome of the analysis reached statistical significance (p = 0.0413), showing greater improvement after citicoline oral solution. There was an increase in the composite score in both arms compared to baseline, but it was significant only for the placebo-citicoline arm (p = 0.0096, p = 0.0007, and p = 0.0006 for the three time-points compared to baseline). The effect of citicoline was stronger in patients with vision-related quality of life more affected by glaucoma at baseline. CONCLUSIONS: This is the first placebo-controlled clinical study evaluating the effect of a medical treatment aiming at improving vision-related quality of life in glaucomatous patients

Measures of socioeconomic status and self-reported glaucoma in the UK Biobank cohort

Purpose: To determine ocular, demographic, and socioeconomic associations with self-reported glaucoma in the UK Biobank.Methods: Biobank is a study of UK residents aged 40–69 years registered with the National Health Service. Data were collected on visual acuity, intraocular pressure (IOP), corneal biomechanics, and questionnaire from 112?690 participants. Relationships between ocular, demographic, and socioeconomic variables with reported diagnosis of glaucoma were examined.Results: In all, 1916 (1.7%) people in UK Biobank reported glaucoma diagnosis. Participants reporting glaucoma were more likely to be older (mean 61.4 vs 56.7 years, P<0.001) and male (2.1% vs 1.4%, P=0.001). The rate of reported glaucoma was significantly higher in Black (3.28%, P<0.001) and Asian (2.14%, P=0.009) participants compared with White participants (1.62%, reference). Cases of reported glaucoma had a higher mean IOP (18?mm?Hg both eyes, P<0.001), lower corneal hysteresis (9.96 right eye, 9.89 left eye, P<0.001), and lower visual acuity (0.09 logMAR right eye, 0.08 logMAR left eye, P<0.001) compared with those without (16?mm?Hg both eyes, hysteresis 10.67 right eye, 10.63 left eye, 0.03 logMAR right eye, 0.02 logMAR left eye). The mean Townsend deprivation index was ?0.72 for those reporting glaucoma and ?0.95 for those without (P<0.001), indicating greater relative deprivation in those reporting glaucoma. Multivariable logistic regression showed that people in the lowest income group (<£18?000/year) were significantly more likely to report a diagnosis of glaucoma compared with any other income level (P<0.01). We observed increasing glaucoma risk across the full range of income categories, with highest risk among those of lowest income, and no evidence of a threshold effect.Conclusions: In a large UK cohort, individuals reporting glaucoma had more adverse socioeconomic characteristics. Study of the mechanisms explaining these effects may aid our understanding of health inequality and will help inform public health interventions

Association of systemic medication use with glaucoma and intraocular pressure: the E3 Consortium

PURPOSE: To investigate the association of commonly used systemic medications with glaucoma and intraocular pressure (IOP) in the European population. DESIGN: Meta-analysis of eleven population-based cohort studies of the European Eye Epidemiology (E3) consortium. PARTICIPANTS: A total of 143240 participants were included in the glaucoma analyses and 47177 participants in the IOP analyses. METHODS: We examined associations of four categories of systemic medications (antihypertensive medications: beta-blockers, diuretics, calcium channel blockers [CCBs], alpha-agonists, angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers; lipid-lowering medications; antidepressants; antidiabetic medications) with glaucoma prevalence and IOP. Glaucoma ascertainment and IOP measurement method were according to individual study protocols. Multivariable regression analyses were carried out in each study and results were pooled using random effects meta-analyses. Associations with antidiabetic medications were examined in diabetic participants only. MAIN OUTCOME MEASURES: Glaucoma prevalence and IOP. RESULTS: In the meta-analyses of our maximally-adjusted multivariable models, use of CCBs was associated with a higher prevalence of glaucoma (odds ratio [OR] with corresponding 95% confidence interval [95% CI]: 1.23 [1.08 to 1.39]). This association was stronger for monotherapy of CCBs with direct cardiac effects (OR [95% CI]: 1.96 [1.23 to 3.12]). The use of other antihypertensive medications, lipid-lowering medications, antidepressants or antidiabetic medications were not clearly associated with glaucoma. Use of systemic beta-blockers was associated with a lower IOP (Beta [95% CI]: -0.33 [-0.57 to -0.08] mmHg). Monotherapy of both selective (Beta [95% CI]: -0.45 [-0.74 to -0.16] mmHg) and non-selective (Beta [95% CI]: -0.54 [-0.94 to -0.15] mmHg) systemic beta-blockers was associated with lower IOP. There was a suggestive association between use of high-ceiling diuretics and lower IOP (Beta [95% CI]: -0.30 [-0.47; -0.14] mmHg), but not when used as monotherapy. Use of other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were not associated with IOP. CONCLUSIONS: We identified a potentially harmful association between use of CCBs and glaucoma prevalence. Additionally, we observed and quantified the association of lower IOP with systemic beta-blocker use. Both findings are potentially important given that glaucoma patients frequently use systemic antihypertensive medications. Determining whether the CCB association is causal should be a research priority

Maturation of the angiotensin II cardiovascular response in the embryonic White Leghorn chicken (Gallus gallus)

Angiotensin II (Ang II) is an important regulator of cardiovascular function in adult vertebrates. Although its role in regulating the adult system has been extensively investigated, the cardiovascular response to Ang II in embryonic vertebrates is relatively unknown. We investigated the potential of Ang II as a regulator of cardiovascular function in embryonic chickens, which lack central nervous system control of cardiovascular function throughout the majority of incubation. The cardiovascular response to Ang II in embryonic chickens was investigated over the final 50% of their development. Ang II produced a dose-dependent increase in arterial pressure on each day of development studied, and the response increased in intensity as development progressed. The Ang II type-1 receptor nonspecific competitive peptide antagonist [Sar1 ile8] Ang II blocked the cardiovascular response to subsequent injections of Ang II on day 21 only. The embryonic pressure response to Ang II (hypertension only) differed from that of adult chickens, in which initial hypotension is followed by hypertension. The constant level of gene expression for the Ang II receptor, in conjunction with an increasing pressure response to the peptide, suggests that two Ang II receptor subtypes are present during chicken development. Collectively, the data indicate that Ang II plays an important role in the cardiovascular development of chickens; however, its role in maintaining basal function requires further study

Five Year Incidence of Visual Field Loss in Adult Chinese. The Beijing Eye Study.

PURPOSE: To describe the cumulative 5 year incidence of visual field loss in adult Chinese in Greater Beijing. METHODS: The Beijing Eye Study 2006 included 3251 subjects (mean age 60.4±10.1 years) who had participated in the Beijing Eye Study 2001 and returned for re-examination. All participants underwent a comprehensive eye examination, including visual field test by frequency doubling threshold perimetry. An abnormal visual field was defined as reduced sensitivity in at least one test location. Incident visual field loss was defined as a change in visual field from normal at baseline to abnormal at follow-up. RESULTS: An incident visual field loss was detected in 273 eyes (4.3±0.5%)/235 subjects (7.3±0.5%). It was significantly associated with higher age (P = 0.001), higher intraocular pressure (P<0.001), and higher fasting blood glucose concentration (P = 0.019). Considering only eyes (n = 140) with a detected cause for visual field loss, the most frequent causes were cataract (68 (48.6%) eyes) followed by glaucoma (23 (16.4%) eyes), diabetic retinopathy (13 (9.3%) eyes), age-related macular degeneration (10 (7.1%) eyes), and myopic degenerative retinopathy (9 (6.4%) eyes). For 133 (48.7%) eyes with a visual field loss, the cause for the VFL remained unclear. CONCLUSIONS: The 5-year incidence of visual field loss was 4.3±0.5% per eye or 7.3±0.5% per subject. It increased significantly with age, intraocular pressure, and fasting blood glucose level. Major causes for the incidence of visual field loss were cataract, glaucoma and diabetic retinopathy